<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04456634</url>
  </required_header>
  <id_info>
    <org_study_id>MMV_Ruxolitinib_19_01</org_study_id>
    <nct_id>NCT04456634</nct_id>
  </id_info>
  <brief_title>Assess Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profile of Ruxolitinib With Artemether-lumefantrine</brief_title>
  <official_title>A Randomised, Single Blind, Placebo Controlled, Phase 1 Trial to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Activity of Ruxolitinib When Co-administered With Artemether-lumefantrine in Healthy Participants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medicines for Malaria Venture</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Southern Star Research Pty Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Nucleus Network Ltd</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Medicines for Malaria Venture</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase 1, single -center study in 2 parts. The study designs for each part are well&#xD;
      established for first-in-human studies and are appropriate to assess safety, tolerability and&#xD;
      preliminary pharmacokinetics&amp; pharmacodynamics.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomised, single-blinded, placebo-controlled, single centre, phase 1 trial.&#xD;
&#xD;
      Eight healthy males or females, aged between 18-55 years old, who meet all of the inclusion&#xD;
      criteria and none of the exclusion criteria, will be enrolled.&#xD;
&#xD;
      The study will be composed of 2 groups to be enrolled sequentially.&#xD;
&#xD;
      • Group 1a (sentinel group): two participants will be randomised single-blinded such that one&#xD;
      participant will receive AL+Rux and the other participant will receive AL+placebo.&#xD;
&#xD;
      After review of the safety and tolerability data up to and including Day 8 from Group 1a by&#xD;
      the Safety Review Committee (SRC), a decision to proceed with Group 1b will be made.&#xD;
&#xD;
      • Group 1b will be composed of 6 participants, to be randomised single-blinded such that five&#xD;
      participants will receive AL+Rux, and one participant will receive AL+placebo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 10, 2020</start_date>
  <completion_date type="Actual">November 17, 2020</completion_date>
  <primary_completion_date type="Actual">November 17, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>2 groups each to be enrolled sequentially. Group 1a will be a sentinel group of 2 participants, and Group 1b will be composed of 6 participants; to be administered either AL + Ruxolitinib or AL + placebo.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Randomised (single blinded; treatment allocation concealed to participants but not Investigator)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participant With Treatment-Related Adverse Events as Assessed by CTCAE V4.03, All of Observed and Self-reported AEs Affected, by Treatment Regimen.</measure>
    <time_frame>up to 28 days after AL+Rux and AL+placebo administration</time_frame>
    <description>Incidence, severity and relationship of observed and self-reported adverse events (AEs) were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Changes of Systolic and Diastolic Blood Pressure</measure>
    <time_frame>up to 28 days after AL+Rux and AL+placebo administration</time_frame>
    <description>Safety signals, trends or significant differences in blood pressure between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Changes in Heart Rate</measure>
    <time_frame>up to 28 days after AL+Rux and AL+placebo administration</time_frame>
    <description>Safety signals, trends or significant differences in heart rate ( beats / min)between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With ECG Changes</measure>
    <time_frame>up to 28 days after AL+Rux and AL+placebo administration</time_frame>
    <description>Safety signals, trends or significant differences in QT, QTcB and QTcF, QRS between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUECt of pSTAT3 Inhibition</measure>
    <time_frame>up to 28 days after AL+Rux and AL+placebo administration</time_frame>
    <description>Area under the effect curve (AUECt) of pSTAT3 inhibition levels</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Malaria</condition>
  <arm_group>
    <arm_group_label>AL&amp;RUX</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral administration of:&#xD;
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AL&amp; Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>20 mg/120 mg artemether-lumefantrine (AL) + Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)</intervention_name>
    <description>Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
    <arm_group_label>AL&amp;RUX</arm_group_label>
    <other_name>Sentinel Group 1 a and 1 b</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>20 mg/120 mg artemether-lumefantrine (AL) + Placebo</intervention_name>
    <description>Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
    <arm_group_label>AL&amp; Placebo</arm_group_label>
    <other_name>Sentinel Group 1 a and 1 b</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female (non-pregnant, non-lactating) aged 18 to 55 years inclusive.&#xD;
&#xD;
          2. Contactable and available for the duration of the trial and for up to two weeks&#xD;
             following the EOS visit.&#xD;
&#xD;
          3. Total body weight greater than or equal to 50 kg, and a body mass index (BMI) within&#xD;
             the range of 18 to 32 kg/m2 (inclusive) at Screening and Day -1. BMI is an estimate of&#xD;
             body weight adjusted for height. It is calculated by dividing the weight in kilograms&#xD;
             by the square of the height in metres.&#xD;
&#xD;
             Health status&#xD;
&#xD;
          4. Certified as healthy by a comprehensive clinical assessment (detailed medical history,&#xD;
             full physical examination and special investigations).&#xD;
&#xD;
          5. Vital signs measured after 5 min in the supine position:&#xD;
&#xD;
               -  Systolic blood pressure (SBP) - 90-140 mmHg,&#xD;
&#xD;
               -  Diastolic blood pressure (DBP) - 40-90 mmHg,&#xD;
&#xD;
               -  Heart rate (HR) 40-100 bpm.&#xD;
&#xD;
          6. ECG parameters for both males and females: QT ≤ 500 msec, QTcF ≤450 msec, QTcB ≤450&#xD;
             msec; PR interval ≤210 msec.&#xD;
&#xD;
          7. Heterosexual female participants of childbearing potential who have, or may have, male&#xD;
             sexual partners during the course of the study should be using an insertable (implant&#xD;
             or IUD), injectable, transdermal or combination oral contraceptive approved by the TGA&#xD;
             combined with a barrier contraceptive from the time of informed consent until EOS.&#xD;
             Abstinent female participants must agree to start a double method if they start a&#xD;
             sexual relationship with a male during the trial. Female participants must not be&#xD;
             planning in vitro fertilisation within the required contraception period.&#xD;
&#xD;
             Women of non-childbearing potential who will not require contraception during the&#xD;
             trial are defined as: surgically sterile (tubal ligation is not considered surgically&#xD;
             sterile), post-menopausal (spontaneous amenorrhoea for ≥12 months, or spontaneous&#xD;
             amenorrhoea for 6-12 months and follicle-stimulating hormone (FSH) ≥40 IU/mL; either&#xD;
             should be together with the absence of oral contraceptive use for &gt;12 months).&#xD;
&#xD;
             Male participants who have, or may have female sexual partners during the course of&#xD;
             the study must agree to use a double method of contraception including condom plus&#xD;
             diaphragm, or condom plus stable insertable (implant or IUD), injectable, transdermal&#xD;
             or combination oral contraceptive by the female partner, from the time of informed&#xD;
             consent through to EOS. Abstinent male participants must agree to start a double&#xD;
             method if they begin a sexual relationship with a female during the trial, and through&#xD;
             to EOS. Male participants with female partners that are surgically sterile or&#xD;
             post-menopausal, or male participants who have undergone sterilisation and have had&#xD;
             testing to confirm the success of the sterilisation, may also be included and will not&#xD;
             be required to use above described methods of contraception.&#xD;
&#xD;
             Regulations&#xD;
&#xD;
          8. Completion of the written informed consent process prior to undertaking any&#xD;
             trial-related procedure.&#xD;
&#xD;
          9. Must be willing and able to communicate and participate in the whole trial.&#xD;
&#xD;
         10. Agree to adhere to Lifestyle Considerations (see Section 4.3.3) throughout trial&#xD;
             duration and be willing to consume 250 mL full-fat milk with each dose of AL.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Medical history and clinical status&#xD;
&#xD;
          1. Known hypersensitivity to ruxolitinib, artesunate or any of its excipients,&#xD;
             artemether, lumefantrine or other artemisinin derivatives, proguanil/atovaquone,&#xD;
             primaquine, or 4-aminoquinolines.&#xD;
&#xD;
          2. Haematology, biochemistry or urinalysis results that are abnormal/outside of the&#xD;
             laboratory normal reference ranges AND are either:&#xD;
&#xD;
               -  Considered clinically signficant by the Principal Investigator or delegate; OR&#xD;
&#xD;
               -  Considered not clinically significant by the Principal Investigator or delegate&#xD;
                  BUT ARE ALSO outside of Sponsor-approved clinically acceptable laboratory ranges&#xD;
                  in Appendix 1.&#xD;
&#xD;
             NOTE: Participants are not excluded if abnormal/out of laboratory normal reference&#xD;
             range results are considered not clinically significant by the Principal Investigator&#xD;
             or delegate AND are within the ranges specified in Appendix 1.&#xD;
&#xD;
          3. Platelets &lt; 200x109/L at Screening or prior to IMP administration is exclusionary. One&#xD;
             re-test is permitted if original test result does not reflect the assumed medical&#xD;
             status of the individual.&#xD;
&#xD;
          4. Participation in any other investigational product trial within 5 half-lives or 12&#xD;
             weeks preceding IMP administration, whichever is longer, or in the exclusion period of&#xD;
             a previous trial according to applicable regulations.&#xD;
&#xD;
          5. Symptomatic postural hypotension at screening and pre-first dose of IMP on Day 1&#xD;
             (confirmed on two consecutive readings), irrespective of the decrease in blood&#xD;
             pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood&#xD;
             pressure ≥20 mmHg within 2-3 min when changing from supine to standing position.&#xD;
&#xD;
          6. History or presence of diagnosed (by an allergist/immunologist) or treated (by a&#xD;
             physician) food or known drug allergies, or any history of anaphylaxis or other severe&#xD;
             allergic reactions including face, mouth, or throat swelling or any difficulty&#xD;
             breathing. Participants with seasonal allergies/hay fever or allergy to animals or&#xD;
             house dust mite that are untreated and asymptomatic at the time of dosing can be&#xD;
             enrolled in the trial.&#xD;
&#xD;
          7. History of convulsion (including drug or vaccine-induced episodes). A medical history&#xD;
             of a single febrile convulsion during childhood is not an exclusion criterion.&#xD;
&#xD;
          8. Presence of current or suspected serious chronic diseases such as cardiac or&#xD;
             autoimmune disease (HIV or other immuno-deficiencies), insulin-dependent and&#xD;
             non-insulin-dependent diabetes, progressive neurological disease, severe malnutrition,&#xD;
             acute or progressive hepatic disease, acute or progressive renal disease, porphyria,&#xD;
             psoriasis, rheumatoid arthritis, asthma (excluding childhood asthma), epilepsy, or&#xD;
             obsessive-compulsive disorder.&#xD;
&#xD;
          9. History of malignancy of any organ system (other than localised and considered cured&#xD;
             basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated,&#xD;
             within five years of screening, regardless of whether there is no evidence of local&#xD;
             recurrence or metastases.&#xD;
&#xD;
         10. Individuals with history of schizophrenia, bipolar disorder psychoses, disorders&#xD;
             requiring lithium, attempted or planned suicide, or any other severe (disabling)&#xD;
             chronic psychiatric diagnosis including generalised anxiety disorder.&#xD;
&#xD;
         11. Individuals who have been hospitalised within five years prior to enrolment for either&#xD;
             a psychiatric illness or due to danger to self or others.&#xD;
&#xD;
         12. History of an episode of mild/moderate depression lasting more than 6 months that&#xD;
             required pharmacological therapy and/or psychotherapy within the last 5 years; or any&#xD;
             episode of major depression. The Beck Depression Inventory (BDI-II) will be used as a&#xD;
             validated tool for the assessment of depression at screening. In addition to the&#xD;
             conditions listed above, individuals with a score of 20 or more on the BDI-II and/or a&#xD;
             response of 1, 2 or 3 for item 9 of this inventory (related to suicidal ideation) will&#xD;
             not be eligible for participation. These individuals will be referred to a general&#xD;
             practitioner or medical specialist as appropriate. Individuals with a BDI-II score of&#xD;
             17 to 19 may be enrolled at the discretion of an Investigator if they do not have a&#xD;
             history of the psychiatric conditions mentioned in this criterion and their mental&#xD;
             state is not considered to pose additional risk to the health of the individual or to&#xD;
             the execution of the trial and interpretation of the data gathered.&#xD;
&#xD;
         13. History of recurrent headache (e.g. tension-type, cluster, or migraine) with a&#xD;
             frequency of ≥2 episodes per month on average and severe enough to require medical&#xD;
             therapy, during the 2 years preceding screening.&#xD;
&#xD;
         14. Acute illness within the 4 weeks prior to screening and prior to IMP administration.&#xD;
&#xD;
         15. Significant inter-current disease of any type, in particular liver, renal, cardiac,&#xD;
             pulmonary, neurologic, rheumatologic, or autoimmune disease by history, physical&#xD;
             examination, and/or laboratory studies including urinalysis.&#xD;
&#xD;
         16. Individual has a clinically significant disease or any condition or disease that might&#xD;
             affect drug absorption, distribution or excretion (e.g. gastrectomy, cholecystectomy,&#xD;
             diarrhoea) or known lactose/dairy intolerance.&#xD;
&#xD;
         17. Participation in any research trial involving blood sampling (more than 300 mL/unit of&#xD;
             blood) within one month prior to IMP administration, or blood donation to Australian&#xD;
             Red Cross Blood Service (Blood Service) or other blood bank during the 8 weeks prior&#xD;
             to IMP administration.&#xD;
&#xD;
         18. Medical requirement for intravenous immunoglobulin or blood transfusions.&#xD;
&#xD;
         19. History or presence of alcohol abuse (alcohol consumption more than 40 g/4 units/4&#xD;
             standard drinks per day), or drug habituation, or any prior intravenous usage of an&#xD;
             illicit substance.&#xD;
&#xD;
         20. Any individual who has ever smoked &gt;1 pack of cigarettes per day for &gt;10 years, or who&#xD;
             currently (within 14 days prior to Screening or prior to IMP administration smokes &gt;5&#xD;
             cigarettes/day.&#xD;
&#xD;
         21. Female who is breastfeeding.&#xD;
&#xD;
         22. Any vaccination within the last 28 days prior to screening or prior to IMP&#xD;
             administration.&#xD;
&#xD;
         23. Prior to screening or IMP administration: any systemic or inhaled corticosteroids,&#xD;
             anti-inflammatory drugs (excluding commonly used over-the-counter anti-inflammatory&#xD;
             drugs such as ibuprofen, acetylsalicylic acid, diclofenac), immunomodulators or&#xD;
             anticoagulants within the past three months. Any topical, nasal or ophthalmic&#xD;
             corticosteroids within the past 2 weeks. Any individual currently receiving or having&#xD;
             previously received immunosuppressive therapy (including systemic steroids,&#xD;
             adrenocorticotrophic hormone or inhaled steroids) at a dose or duration potentially&#xD;
             associated with hypothalamic-pituitary-adrenal axis suppression within the past year.&#xD;
&#xD;
         24. Use of antidepressant medication in the past 12 months prior to screening or prior to&#xD;
             IMP administration.&#xD;
&#xD;
         25. Use of any other medication except contraceptives (including herbal, vitamin&#xD;
             supplement, OTC or prescription) within 14 days or five half-lives (whichever is&#xD;
             longest) prior to IMP administration. Participants areCONFIDENTIAL Page 7 of 78&#xD;
             requested to refrain from taking non-approved concomitant medications from recruitment&#xD;
             until the conclusion of the trial.&#xD;
&#xD;
         26. Cardiac/QT risk:&#xD;
&#xD;
               -  Family history of sudden death or of congenital prolongation of the QTc interval&#xD;
                  or known congenital prolongation of the QTc interval or any clinical condition&#xD;
                  known to prolong the QTc interval.&#xD;
&#xD;
               -  History of symptomatic cardiac arrhythmias or with clinically relevant&#xD;
                  bradycardia.&#xD;
&#xD;
               -  Electrolyte disturbances, particularly hypokalaemia, hypocalcaemia, or&#xD;
                  hypomagnesaemia.&#xD;
&#xD;
               -  ECG abnormalities in the standard 12-lead ECG (at screening or prior to IMP&#xD;
                  administration) which in the opinion of an Investigator is clinically relevant or&#xD;
                  will interfere with the ECG analyses.&#xD;
&#xD;
             General conditions&#xD;
&#xD;
         27. Any individual who, in the judgement of an Investigator, is likely to be non-compliant&#xD;
             during the trial, or is unable to cooperate because of a language problem or poor&#xD;
             mental development.&#xD;
&#xD;
         28. Any individual for whom study participation would pose an additional safety risk as&#xD;
             assessed by the Principal Investigator.&#xD;
&#xD;
         29. Any individual who is an Investigator, research assistant, pharmacist, trial&#xD;
             coordinator, or other staff thereof, directly involved in conducting the trial.&#xD;
&#xD;
         30. Any individual without good peripheral venous access. Biological status&#xD;
&#xD;
         31. Positive result on any of the following tests: hepatitis B surface antigen (HBs Ag),&#xD;
             anti-hepatitis B core antibodies (anti-HBc Ab), anti-hepatitis C virus (anti-HCV)&#xD;
             antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and&#xD;
             anti-HIV2 Ab).&#xD;
&#xD;
         32. Recent herpes zoster infection (within the previous 6 months) as determined by&#xD;
             clinical history.&#xD;
&#xD;
         33. Positive result for M. tuberculosis infection by QuantiFERON-TB Gold assay.&#xD;
&#xD;
         34. Positive urine drug test for any drug listed in Section 7.4.5. Any individual testing&#xD;
             positive for acetaminophen (paracetamol) at screening and/or pre-dose may still be&#xD;
             eligible for trial participation at the discretion of the Principal Investigator or&#xD;
             delegate.&#xD;
&#xD;
         35. Positive alcohol breath test.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul Griffin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nucleus Network Corporate</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nucleus Network Brisbane</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>June 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <results_first_submitted>May 4, 2021</results_first_submitted>
  <results_first_submitted_qc>June 18, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">July 9, 2021</results_first_posted>
  <last_update_submitted>June 18, 2021</last_update_submitted>
  <last_update_submitted_qc>June 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Saftey</keyword>
  <keyword>Tolerability</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Malaria</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lumefantrine</mesh_term>
    <mesh_term>Artemether</mesh_term>
    <mesh_term>Artemether, Lumefantrine Drug Combination</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 7, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/34/NCT04456634/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 16, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/34/NCT04456634/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 8 eligible participants were recruited at in the time period between 24 Aug 2020 and 19 Oct 2020 at Nucleus Network Brisbane clinic.</recruitment_details>
      <pre_assignment_details>No wash out phase, no run-in phase. All eligible participants were dosed to the allocated doses on day 1. The study was composed of 2 groups to be enrolled sequentially.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>AL&amp;RUX</title>
          <description>Oral administration of:&#xD;
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)&#xD;
20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux): Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
        </group>
        <group group_id="P2">
          <title>AL&amp; Placebo</title>
          <description>20 mg/120 mg artemether-lumefantrine (AL) + Placebo&#xD;
20 mg/120 mg artemether-lumefantrine (AL) + Placebo: Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>AL&amp;RUX</title>
          <description>Oral administration of:&#xD;
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)&#xD;
20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux): Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
        </group>
        <group group_id="B2">
          <title>AL&amp; Placebo</title>
          <description>20 mg/120 mg artemether-lumefantrine (AL) + Placebo&#xD;
20 mg/120 mg artemether-lumefantrine (AL) + Placebo: Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="2"/>
            <count group_id="B3" value="8"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.3" spread="11.8"/>
                    <measurement group_id="B2" value="30.0" spread="12.7"/>
                    <measurement group_id="B3" value="27.3" spread="27.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Australia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participant With Treatment-Related Adverse Events as Assessed by CTCAE V4.03, All of Observed and Self-reported AEs Affected, by Treatment Regimen.</title>
        <description>Incidence, severity and relationship of observed and self-reported adverse events (AEs) were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.</description>
        <time_frame>up to 28 days after AL+Rux and AL+placebo administration</time_frame>
        <population>All participants who received at least one dose of treatment</population>
        <group_list>
          <group group_id="O1">
            <title>AL&amp;RUX</title>
            <description>Oral administration of:&#xD;
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)&#xD;
20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux): Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
          </group>
          <group group_id="O2">
            <title>AL&amp; Placebo</title>
            <description>20 mg/120 mg artemether-lumefantrine (AL) + Placebo&#xD;
20 mg/120 mg artemether-lumefantrine (AL) + Placebo: Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participant With Treatment-Related Adverse Events as Assessed by CTCAE V4.03, All of Observed and Self-reported AEs Affected, by Treatment Regimen.</title>
          <description>Incidence, severity and relationship of observed and self-reported adverse events (AEs) were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.</description>
          <population>All participants who received at least one dose of treatment</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Changes of Systolic and Diastolic Blood Pressure</title>
        <description>Safety signals, trends or significant differences in blood pressure between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.</description>
        <time_frame>up to 28 days after AL+Rux and AL+placebo administration</time_frame>
        <population>All participants who received at least one dose of treatment</population>
        <group_list>
          <group group_id="O1">
            <title>AL&amp;RUX</title>
            <description>Oral administration of:&#xD;
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)&#xD;
20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux): Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
          </group>
          <group group_id="O2">
            <title>AL&amp; Placebo</title>
            <description>20 mg/120 mg artemether-lumefantrine (AL) + Placebo&#xD;
20 mg/120 mg artemether-lumefantrine (AL) + Placebo: Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Changes of Systolic and Diastolic Blood Pressure</title>
          <description>Safety signals, trends or significant differences in blood pressure between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.</description>
          <population>All participants who received at least one dose of treatment</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Changes in Heart Rate</title>
        <description>Safety signals, trends or significant differences in heart rate ( beats / min)between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.</description>
        <time_frame>up to 28 days after AL+Rux and AL+placebo administration</time_frame>
        <population>All participants who received at least one dose of treatment</population>
        <group_list>
          <group group_id="O1">
            <title>AL&amp;RUX</title>
            <description>Oral administration of:&#xD;
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)&#xD;
20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux): Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
          </group>
          <group group_id="O2">
            <title>AL&amp; Placebo</title>
            <description>20 mg/120 mg artemether-lumefantrine (AL) + Placebo&#xD;
20 mg/120 mg artemether-lumefantrine (AL) + Placebo: Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Changes in Heart Rate</title>
          <description>Safety signals, trends or significant differences in heart rate ( beats / min)between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.</description>
          <population>All participants who received at least one dose of treatment</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With ECG Changes</title>
        <description>Safety signals, trends or significant differences in QT, QTcB and QTcF, QRS between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.</description>
        <time_frame>up to 28 days after AL+Rux and AL+placebo administration</time_frame>
        <population>All participants who received at least one dose of treatment</population>
        <group_list>
          <group group_id="O1">
            <title>AL&amp;RUX</title>
            <description>Oral administration of:&#xD;
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)&#xD;
20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux): Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
          </group>
          <group group_id="O2">
            <title>AL&amp; Placebo</title>
            <description>20 mg/120 mg artemether-lumefantrine (AL) + Placebo&#xD;
20 mg/120 mg artemether-lumefantrine (AL) + Placebo: Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With ECG Changes</title>
          <description>Safety signals, trends or significant differences in QT, QTcB and QTcF, QRS between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.</description>
          <population>All participants who received at least one dose of treatment</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUECt of pSTAT3 Inhibition</title>
        <description>Area under the effect curve (AUECt) of pSTAT3 inhibition levels</description>
        <time_frame>up to 28 days after AL+Rux and AL+placebo administration</time_frame>
        <population>All participants who received at least one dose of treatment</population>
        <group_list>
          <group group_id="O1">
            <title>AL&amp;RUX</title>
            <description>Oral administration of:&#xD;
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)&#xD;
20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux): Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
          </group>
          <group group_id="O2">
            <title>AL&amp; Placebo</title>
            <description>20 mg/120 mg artemether-lumefantrine (AL) + Placebo&#xD;
20 mg/120 mg artemether-lumefantrine (AL) + Placebo: Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
          </group>
        </group_list>
        <measure>
          <title>AUECt of pSTAT3 Inhibition</title>
          <description>Area under the effect curve (AUECt) of pSTAT3 inhibition levels</description>
          <population>All participants who received at least one dose of treatment</population>
          <units>ng.hr/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="551" spread="86.9"/>
                    <measurement group_id="O2" value="186" spread="64.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were recorded from time of first dose of IMP until day 29 ( End of study visit) or early termination, approximately 29 days.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>AL&amp;RUX</title>
          <description>Oral administration of:&#xD;
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)&#xD;
20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux): Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
        </group>
        <group group_id="E2">
          <title>AL&amp; Placebo</title>
          <description>20 mg/120 mg artemether-lumefantrine (AL) + Placebo&#xD;
20 mg/120 mg artemether-lumefantrine (AL) + Placebo: Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (Unspecified)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Vessel puncture site bruise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscular back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>A PK drug-drug interaction between artemether and Rux cannot be excluded, and more data is needed to properly characterize such a potential interaction.&#xD;
Investigation of possible PK drug-drug interactions were not within the scope of this study, due to small participant numbers, differing PK blood sampling schemes on Days 1 and 3, variability of artemether and lumefantrine PK parameters in the AL+Rux treatment group, and absence of a Rux-only treatment group.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Jacques Herve</name_or_title>
      <organization>Medicines for Malaria Venture (MMV)</organization>
      <phone>+41 79 370 40 63</phone>
      <email>hervej@mmv.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04456634
org study id: MMV_Ruxolitinib_19_01
nct id: NCT04456634
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Phase 1, single -center study in 2 parts. The study designs for each part are well
      established for first-in-human studies and are appropriate to assess safety, tolerability and
      preliminary pharmacokinetics& pharmacodynamics.
This is a randomised, single-blinded, placebo-controlled, single centre, phase 1 trial.

      Eight healthy males or females, aged between 18-55 years old, who meet all of the inclusion
      criteria and none of the exclusion criteria, will be enrolled.

      The study will be composed of 2 groups to be enrolled sequentially.

      • Group 1a (sentinel group): two participants will be randomised single-blinded such that one
      participant will receive AL+Rux and the other participant will receive AL+placebo.

      After review of the safety and tolerability data up to and including Day 8 from Group 1a by
      the Safety Review Committee (SRC), a decision to proceed with Group 1b will be made.

      • Group 1b will be composed of 6 participants, to be randomised single-blinded such that five
      participants will receive AL+Rux, and one participant will receive AL+placebo.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: 2 groups each to be enrolled sequentially. Group 1a will be a sentinel group of 2 participants, and Group 1b will be composed of 6 participants; to be administered either AL + Ruxolitinib or AL + placebo.
primary purpose: Treatment
masking: Single (Participant)
masking description: Randomised (single blinded; treatment allocation concealed to participants but not Investigator)
measure: Number of Participant With Treatment-Related Adverse Events as Assessed by CTCAE V4.03, All of Observed and Self-reported AEs Affected, by Treatment Regimen.
time frame: up to 28 days after AL+Rux and AL+placebo administration
description: Incidence, severity and relationship of observed and self-reported adverse events (AEs) were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.
measure: Number of Participants With Changes of Systolic and Diastolic Blood Pressure
time frame: up to 28 days after AL+Rux and AL+placebo administration
description: Safety signals, trends or significant differences in blood pressure between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.
measure: Number of Participants With Changes in Heart Rate
time frame: up to 28 days after AL+Rux and AL+placebo administration
description: Safety signals, trends or significant differences in heart rate ( beats / min)between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.
measure: Number of Participants With ECG Changes
time frame: up to 28 days after AL+Rux and AL+placebo administration
description: Safety signals, trends or significant differences in QT, QTcB and QTcF, QRS between treatment groups were were reported during the study up to 28 days after AL+Rux and AL+Placebo administration in all participants by treatment regimens.
measure: AUECt of pSTAT3 Inhibition
time frame: up to 28 days after AL+Rux and AL+placebo administration
description: Area under the effect curve (AUECt) of pSTAT3 inhibition levels
arm group label: AL&RUX
arm group type: Experimental
description: Oral administration of:
• 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)
arm group label: AL& Placebo
arm group type: Placebo Comparator
description: 20 mg/120 mg artemether-lumefantrine (AL) + Placebo
intervention type: Drug
intervention name: 20 mg/120 mg artemether-lumefantrine (AL) + 20 mg ruxolitinib phosphate (Rux)
description: Rux administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
arm group label: AL&RUX
other name: Sentinel Group 1 a and 1 b
intervention type: Other
intervention name: 20 mg/120 mg artemether-lumefantrine (AL) + Placebo
description: Placebo administered 2 hours after AL administration, twice daily (b.i.d) for 3 consecutive days (6 doses in total).
arm group label: AL& Placebo
other name: Sentinel Group 1 a and 1 b
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Paul Griffin, MD
role: Principal Investigator
affiliation: Nucleus Network Corporate
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Malaria
mesh term: Lumefantrine
mesh term: Artemether
mesh term: Artemether, Lumefantrine Drug Combination
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: A PK drug-drug interaction between artemether and Rux cannot be excluded, and more data is needed to properly characterize such a potential interaction.
Investigation of possible PK drug-drug interactions were not within the scope of this study, due to small participant numbers, differing PK blood sampling schemes on Days 1 and 3, variability of artemether and lumefantrine PK parameters in the AL+Rux treatment group, and absence of a Rux-only treatment group.
point of contact: 