<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/NCT03771885</url>
  </required_header>
  <id_info>
    <org_study_id>1408-0004</org_study_id>
    <secondary_id>2017-004948-38</secondary_id>
    <nct_id>NCT03771885</nct_id>
  </id_info>
  <brief_title>BI 705564 in Patients With Systemic Lupus Erythematosus (SLE)</brief_title>
  <official_title>A Phase Ib, Multicentre, Randomised, Double-blind, Placebo Controlled, 8 Week Crossover Study to Assess the Safety, Tolerability and Pharmacokinetics of Orally Administered BI 705564 in Patients With Systemic Lupus Erythematosus.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <oversight_info>
    <has_dmc>No</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>
      The main objective of this study is to assess the safety, tolerability and pharmacokinetics&#xD;
      of orally administered BI 705564 in patients with systemic lupus erythematosus&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Based on a strategic decision, the application for the trial has been withdrawn before&#xD;
    initiation.&#xD;
  </why_stopped>
  <start_date type="Anticipated">March 16, 2019</start_date>
  <completion_date type="Anticipated">January 7, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 21, 2019</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The primary endpoint to assess safety and tolerability of BI 705564 is the number of patients with drug related Adverse Events</measure>
    <time_frame>Up to 73 Days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number and severity of Adverse Events</measure>
    <time_frame>Up to 87 Days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with Adverse Events</measure>
    <time_frame>Up to 87 Days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with Serious Adverse Events</measure>
    <time_frame>Up to 87 Days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in BILAG</measure>
    <time_frame>Up to 87 Days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in SLEDAI-2K</measure>
    <time_frame>Up to 87 Days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Lupus Erythematosus, Systemic</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 weeks place followed by 4 weeks IMP</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 weeks IMP followed by 4 weeks placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 705564</intervention_name>
    <description>Film-coated Tablet</description>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Film-coated Tablet</description>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ≥ 18 years at screening.&#xD;
&#xD;
          -  Diagnosis of systemic lupus erythematosus (SLE) at least 6 months prior to screening&#xD;
             according to SLICC 2012 criteria; at least 4 criteria must be documented.&#xD;
&#xD;
          -  Positive test results for anti-nuclear antibody (ANA) (human epithelial cell-2 ANA&#xD;
             greater than or equal to [&gt;=] 1:80) and/or anti-dsDNA antibody at the Screening visit.&#xD;
             To be performed by Central Laboratory.&#xD;
&#xD;
          -  At screening visit a &quot;clinical&quot; Systemic Lupus Erythematosus Disease Activity Index&#xD;
             (2K), (SLEDAI 2K) score of ≥ 4 points. The &quot;clinical&quot; score is the SLEDAI 2K&#xD;
             assessment score without the inclusion of points attributable to any blood laboratory&#xD;
             results including immunologic measures. Neurologic descriptors of the SLEDAI 2K are&#xD;
             not counted towards the SLEDAI 2K study entry criteria.&#xD;
&#xD;
          -  Has received all scheduled vaccines according to local guidelines and Investigator&#xD;
             judgement. Live or live-attenuated virus vaccines are not permitted within 1 month&#xD;
             prior to screening or during screening. For all other vaccines there must be at least&#xD;
             2 weeks between the vaccination(s) and the date of randomization at Day 1.&#xD;
&#xD;
          -  For male patients: Men who are permanently sterile by bilateral orchidectomy are not&#xD;
             required to use contraception. Men whose partner (or potential partner) is a women of&#xD;
             childbearing potential*, for the duration of the study (including 30 days after the&#xD;
             last dose of study drug) must use a condom. For female patients: Women of childbearing&#xD;
             potential* must be willing and able to use a double-barrier contraception (barrier in&#xD;
             the meaning of method) with at least one highly effective method of birth control per&#xD;
             ICH M3(R2) that result in a low failure rate of less than 1% per year when used&#xD;
             consistently and correctly for the duration of the study including 4 weeks after the&#xD;
             last dose of study drug. Medically accepted methods of contraception in this study&#xD;
             are:&#xD;
&#xD;
               -  Combined (oestrogen and progestogen containing) hormonal birth control associated&#xD;
                  with inhibition of ovulation in combination with male condom.&#xD;
&#xD;
               -  Progestogen-only hormonal birth control associated with inhibition of ovulation&#xD;
                  in combination with male condom.&#xD;
&#xD;
               -  Intrauterine device (IUD) and intrauterine hormone-releasing system (IUS) in&#xD;
                  combination with male condom Or&#xD;
&#xD;
                    -  The patient must have only vasectomized sexual partner(s) (vasectomy at&#xD;
                       least 1 year prior to enrolment), Or&#xD;
&#xD;
                    -  The patient must follow true abstinence from male-female sex. This is&#xD;
                       defined as being in line with the preferred and usual lifestyle of the&#xD;
                       patient. Periodic abstinence e.g. calendar, ovulation, symptothermal,&#xD;
                       post-ovulation methods; declaration of abstinence for the duration of&#xD;
                       exposure to IMP; and withdrawal are not acceptable.&#xD;
&#xD;
                         -  A woman is considered of childbearing potential (WOCBP), i.e. fertile,&#xD;
                            following menarche and until becoming post-menopausal unless&#xD;
                            permanently sterile. Permanent sterilization methods include&#xD;
                            hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Tubal&#xD;
                            ligation is NOT a method of permanent sterilisation. A postmenopausal&#xD;
                            state is defined as no menses for 12 months without an alternative&#xD;
                            medical cause.&#xD;
&#xD;
          -  Signed and dated written informed consent in accordance with ICH-GCP and local&#xD;
             legislation prior to admission to the trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active clinically significant neuropsychiatric SLE or any BILAG A score for a&#xD;
             neuropsychiatric manifestation or in the ophthalmic domain within the past 12 months.&#xD;
&#xD;
          -  Drug-induced Lupus.&#xD;
&#xD;
          -  Other autoimmune diseases such as Rheumatoid Arthritis, Crohn's, scleroderma,&#xD;
             psoriasis, Celiac disease, Graves'disease, thyroid disease, with the following&#xD;
             exceptions:&#xD;
&#xD;
               -  Sjögren syndrome if this is secondary to their SLE is permissible.&#xD;
&#xD;
               -  Patients with features of mixed connective tissue disease may be included if this&#xD;
                  is secondary to their SLE and is, in the Investigator's opinion not considered to&#xD;
                  be significant.&#xD;
&#xD;
               -  Patients with APS antibodies may be included unless they are excluded due to&#xD;
                  exclusion anti-coagulation medication (see exclusion criteria below for details)&#xD;
                  or if they have a history of thromboembolic events or miscarriage.&#xD;
&#xD;
               -  Diabetes if this is considered by the Investigator to be well controlled and&#xD;
                  there is no evidence of retinopathy or nephropathy.&#xD;
&#xD;
          -  Initiation or change in dose of anti-malarial treatment after the screening visit.&#xD;
&#xD;
          -  Patients who require fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin&#xD;
             K antagonists, dabigatran, heparin, hirudin, etc.) or high dose antiplatelet therapy.&#xD;
&#xD;
          -  Within 2 weeks prior to Screening or during Screening: use of oral corticosteroids&#xD;
             greater than (&gt;) 15 mg daily prednisone or an equivalent dose, use of any injectable&#xD;
             corticosteroids, or change in dose of corticosteroids. For patients continuing on oral&#xD;
             corticosteroids the dose must be stable for 4 weeks prior to randomisation.&#xD;
&#xD;
          -  After consent, initiation or change in dose of angiotensin-converting enzyme inhibitor&#xD;
             or angiotensin receptor blocker.&#xD;
&#xD;
          -  Initiation of regular nonsteroidal anti-inflammatory drugs (NSAIDs) use within 2 weeks&#xD;
             prior to Screening. Regular use defined as 3 consecutive days.&#xD;
&#xD;
          -  Within 2 months prior to Screening or during Screening: initiation of or change in&#xD;
             dose of methotrexate, mycophenolate (mofetil or sodium), or azathioprine.&#xD;
&#xD;
          -  Within 4 weeks prior to Screening or during Screening, use of cyclosporine or&#xD;
             tacrolimus.&#xD;
&#xD;
          -  Within 3 months prior to Screening or during Screening: use of cyclophosphamide or&#xD;
             chlorambucil.&#xD;
&#xD;
          -  Within 3 months prior to Screening or during Screening, use of leflunomide, abatacept,&#xD;
             anti-tumor necrosis factor alpha agents, intravenous immunoglobulin, plasmapheresis,&#xD;
             or other disease modifying, immunosuppressive, or immunomodulatory therapies not&#xD;
             otherwise specified in protocol.&#xD;
&#xD;
          -  Within 12 months prior to screening or during screening: use of anti-CD20 or anti-CD22&#xD;
             biological medications or any other B cell-depleting medication. If a patient has had&#xD;
             rituximab more than 6 months ago and has a normal CD-19 count then they may be&#xD;
             included. A historic local lab value may be used to confirm this. For B-cell&#xD;
             modulating therapies including atacicept these are excluded within 6 months apart from&#xD;
             blisibimod and belimumab which are excluded within 3 months. Type I-IFN interferon&#xD;
             antagonists such as anifrolumab are excluded within 6 months.&#xD;
&#xD;
          -  Ustekinumab within 6 months of screening.&#xD;
&#xD;
          -  JAK inhibitors within the last 12 months before screening visit.&#xD;
&#xD;
          -  Active clinically significant viral, bacterial or fungal infection, or any serious&#xD;
             episode of infection requiring hospitalization within the last 6 months. If the&#xD;
             infection is not active or clinical significant or required hospitalization the&#xD;
             patient may be included as long as they have not taken antibiotics more than 4 weeks&#xD;
             prior to screening.&#xD;
&#xD;
          -  Chronic Hepatitis B, HIV, history of active TB.&#xD;
&#xD;
               -  A patient with an indeterminate or positive TB test result at screening may be&#xD;
                  enrolled if a thorough investigation by a qualified physician determines that&#xD;
                  they do not have active TB or untreated latent TB.&#xD;
&#xD;
               -  In the case of Anti-HBc antibody positive result but HBs antigen negative then&#xD;
                  Hepatitis B DNA can be measured at a local lab. If Hepatitis B DNA is positive&#xD;
                  the patient will be excluded, if Hepatitis B DNA is negative then the patient can&#xD;
                  be included.&#xD;
&#xD;
          -  Immunoglobulin G (IgG) less than the lower limit of normal at screening.&#xD;
&#xD;
          -  Estimated glomerular filtration rate of less than (&lt;) 60 milliliter per minute per&#xD;
             1.73 square meter (mL/min/1.73 m^2) by the CKD-EPI (2009) Creatinine Equation, or&#xD;
             recent decline in kidney function, defined as decrease within the last 2 months prior&#xD;
             to screening:&#xD;
&#xD;
             -- as a reduction in eGFR of &gt;=20% and below lower limit of normal (90 mL/ min/&#xD;
             1.73m2).&#xD;
&#xD;
          -  Proteinuria &gt; 2 g/d or urine protein/urine creatinine ratio &gt;2 mg/mg at screening.&#xD;
&#xD;
          -  Clinically significant other renal disease based on investigator judgement (e.g.&#xD;
             postinfectious GN, pyelonephritis)&#xD;
&#xD;
          -  Major surgery (major according to the investigator's assessment) performed within 12&#xD;
             weeks prior to randomization or planned during the trial.&#xD;
&#xD;
          -  Any documented active or suspected malignancy or history of malignancy within 5 years&#xD;
             prior to screening, except appropriately treated basal cell carcinoma of the skin or&#xD;
             in situ carcinoma of uterine cervix.&#xD;
&#xD;
          -  Patients who must or wish to continue the intake of restricted medications or any drug&#xD;
             considered likely to interfere with the safe conduct of the trial.&#xD;
&#xD;
          -  Previous randomisation into this trial.&#xD;
&#xD;
          -  Currently enrolled in another investigational device or drug trial,&#xD;
&#xD;
               -  or less than 30 days or 5 half-lives (whichever is longer),since ending another&#xD;
                  investigational device or drug trial(s) for an oral agent which is not specified&#xD;
                  in any other exclusion criteria,&#xD;
&#xD;
               -  or less than 12 months since ending another investigational device or drug&#xD;
                  trial(s) for a biological agent which is not specified in exclusion criteria&#xD;
&#xD;
               -  or receiving other investigational treatment(s).&#xD;
&#xD;
          -  Chronic alcohol or drug abuse or any condition that, in the investigator's opinion,&#xD;
             makes them an unreliable trial patient or unlikely to complete the trial.&#xD;
&#xD;
          -  Women who are pregnant, nursing, or who plan to become pregnant in the timeline of the&#xD;
             trial.&#xD;
&#xD;
          -  Uncontrolled hypertension or other haematologic conditions (except SLE). Diabetes&#xD;
             mellitus if poorly controlled according to investigator or known diabetic nephropathy&#xD;
             or retinopathy.&#xD;
&#xD;
          -  Thrombocyte count at screening 70,000/μl or less.&#xD;
&#xD;
          -  Known hypersensitivity to the study drug or their excipients.&#xD;
&#xD;
          -  Patients with known ocular complications apart from dry eyes and mild cataracts in the&#xD;
             opinion of an ophthalmologist.&#xD;
&#xD;
          -  A disease or condition which in the opinion of the investigator may interfere with&#xD;
             testing procedures or put the patient at risk when participating in this trial.&#xD;
&#xD;
          -  History of pancreatitis of any aetiology&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <last_update_submitted>November 12, 2021</last_update_submitted>
  <last_update_submitted_qc>November 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lupus Erythematosus, Systemic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:&#xD;
studies in products where Boehringer Ingelheim is not the license holder;&#xD;
studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;&#xD;
studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).&#xD;
For more details refer to: https://www.mystudywindow.com/msw/datasharing</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03771885
org study id: 1408-0004
secondary id: 2017-004948-38
nct id: NCT03771885
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The main objective of this study is to assess the safety, tolerability and pharmacokinetics
      of orally administered BI 705564 in patients with systemic lupus erythematosus
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: The primary endpoint to assess safety and tolerability of BI 705564 is the number of patients with drug related Adverse Events
time frame: Up to 73 Days
measure: Number and severity of Adverse Events
time frame: Up to 87 Days
measure: Number of patients with Adverse Events
time frame: Up to 87 Days
measure: Number of patients with Serious Adverse Events
time frame: Up to 87 Days
measure: Change from baseline in BILAG
time frame: Up to 87 Days
measure: Change from baseline in SLEDAI-2K
time frame: Up to 87 Days
arm group label: Group A
arm group type: Experimental
description: 4 weeks place followed by 4 weeks IMP
arm group label: Group B
arm group type: Experimental
description: 4 weeks IMP followed by 4 weeks placebo
intervention type: Drug
intervention name: BI 705564
description: Film-coated Tablet
arm group label: Group A
arm group label: Group B
intervention type: Drug
intervention name: Placebo
description: Film-coated Tablet
arm group label: Group A
arm group label: Group B
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
responsible party type: Sponsor
mesh term: Lupus Erythematosus, Systemic
sharing ipd: No
ipd description: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:
studies in products where Boehringer Ingelheim is not the license holder;
studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).
For more details refer to: https://www.mystudywindow.com/msw/datasharing