<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/NCT03292302</url>
  </required_header>
  <id_info>
    <org_study_id>EL-006</org_study_id>
    <nct_id>NCT03292302</nct_id>
  </id_info>
  <brief_title>Phase 1 Study of ELX-02 in Healthy Adults</brief_title>
  <official_title>A Phase 1a, Randomized, Double-blinded, Placebo-Controlled, Single Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ELX-02 in Healthy Adult Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eloxx Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>SGS Life Sciences, a division of SGS Belgium NV</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Eloxx Pharmaceuticals, Inc.</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 Ascending Dose Study in Normal Healthy Volunteers&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a study in humans of ELX-02, an advanced synthetic aminoglycoside optimized as a&#xD;
      translational read-through drug (TRID) for the treatment of genetic conditions caused by&#xD;
      nonsense mutations. This is a classical Phase 1a study designed as a randomized,&#xD;
      double-blinded, placebo-controlled, single dose escalation to evaluate the safety,&#xD;
      tolerability and pharmacokinetics of ELX-02 in healthy adult volunteers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 26, 2017</start_date>
  <completion_date type="Actual">December 15, 2017</completion_date>
  <primary_completion_date type="Actual">December 15, 2017</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>0-10 days</time_frame>
    <description>Incidence and characteristics of adverse events occurring following single doses of ELX-02</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics: Maximum plasma concentration (Cmax)</measure>
    <time_frame>0-10 days</time_frame>
    <description>Cmax will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics: Time at which Cmax occurs (tmax)</measure>
    <time_frame>0-10 days</time_frame>
    <description>tmax will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics: Area under the plasma concentration-time curve calculated from time of administration to time 24h (AUC24h)</measure>
    <time_frame>0-10 days</time_frame>
    <description>AUC24h will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics: Area under the plasma concentration-time curve calculated from time of administration to time 48h (AUC48h)</measure>
    <time_frame>0-10 days</time_frame>
    <description>AUC48h will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics: Area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf)</measure>
    <time_frame>0-10 days</time_frame>
    <description>AUCinf will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics: Mean residence time (MRT)</measure>
    <time_frame>0-10 days</time_frame>
    <description>MRT will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics: Elimination half-life (t1/2)</measure>
    <time_frame>0-10 days</time_frame>
    <description>t1/2 will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics: Volume of distribution (Vd/F)</measure>
    <time_frame>0-10 days</time_frame>
    <description>Vd/F will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics: Clearance (CL/F)</measure>
    <time_frame>0-10 days</time_frame>
    <description>CL/F will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Genetic Disease</condition>
  <condition>Nonsense Mutation</condition>
  <arm_group>
    <arm_group_label>Placebo Comparator Arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Active treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>ELX-02</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo comparator</description>
    <arm_group_label>Placebo Comparator Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ELX-02</intervention_name>
    <description>Synthetic aminoglycoside</description>
    <arm_group_label>Active treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Subjects must meet all of the following inclusion criteria to be eligible for enrollment&#xD;
        into the study:&#xD;
&#xD;
          1. Be able and willing to provide written Informed Consent indicating that the subject&#xD;
             has been informed of all pertinent aspects of the study.&#xD;
&#xD;
          2. Healthy female subjects and male subjects who, at the time of screening, are between&#xD;
             the ages of 18 and 45 years, inclusive.&#xD;
&#xD;
             Healthy is defined as no clinically relevant abnormalities identified by a detailed&#xD;
             medical history, full physical examination, including blood pressure (BP) and pulse&#xD;
             rate measurement, 12-lead electrocardiogram (ECG), and clinical laboratory tests.&#xD;
&#xD;
          3. Female subjects of nonchildbearing potential must meet at least one of the following&#xD;
             criteria:&#xD;
&#xD;
               -  Achieved postmenopausal status, defined as follows: cessation of regular menses&#xD;
                  for at least 12 consecutive months with no alternative pathological or&#xD;
                  physiological cause; post-menopausal status will be confirmed by a serum&#xD;
                  follicle-stimulating hormone level;&#xD;
&#xD;
               -  Have undergone a documented hysterectomy and/or bilateral oophorectomy;&#xD;
&#xD;
               -  Have medically confirmed ovarian failure. All other female subjects (including&#xD;
                  females with tubal ligations) will be considered to be of childbearing potential&#xD;
                  and may be enrolled if they have negative pregnancy tests at screening and&#xD;
                  admission day and agree to use a highly effective method of contraception for 14&#xD;
                  days before study drug administration and 28 days after study drug&#xD;
                  administration. Female subjects of childbearing potential must agree to undergo&#xD;
                  repeated pregnancy tests. For highly effective methods of contraception include&#xD;
                  see Section 6.5.1.&#xD;
&#xD;
          4. Male subjects must be willing to use an effective method of contraception. They must&#xD;
             agree to use a condom consistently and correctly, during the course of the study until&#xD;
             28 days after study drug administration.&#xD;
&#xD;
          5. Not using any prescription medication and dietary supplements within 30 days or 5&#xD;
             half-lives (whichever is longer) prior to the administration of study drug&#xD;
             administration, except for contraceptives - nor be taking any over-the-counter (OTC)&#xD;
             herbal or medicinal products. As an exception, acetaminophen/paracetamol may be used&#xD;
             at doses of ≤ 2 g/day. Aspirin and non steroidal anti inflammatory drugs (NSAIDs)&#xD;
             should not be administered within 1 week of study dose.&#xD;
&#xD;
          6. Non-smoking and no use of any tobacco or nicotine products (by declaration) for a&#xD;
             period of at least 6 months prior to screening visit.&#xD;
&#xD;
          7. Be on no medication with potential to impair renal function (e.g., NSAIDs) or with&#xD;
             ototoxic potential (e.g., quinine, salicylates, aminoglycosides).&#xD;
&#xD;
          8. Normal renal function (glomular filtration rate &gt;60 mL/min) based on creatinine plasma&#xD;
             concentration and the Modification of Diet in Renal Disease equation for estimated&#xD;
             glomular filtration rate. Subjects with lower Modification of Diet in Renal Disease&#xD;
             (MDRD) clearance can be included on the condition that they have a normal 24h&#xD;
             creatinine clearance (determined by a 24h urine collection).&#xD;
&#xD;
          9. Negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg),&#xD;
             hepatitis C virus antibody (HCV Ab) serology tests at screening.&#xD;
&#xD;
         10. No history of alcohol or drug of abuse (DOA). Negative urine test for DOA and alcohol&#xD;
             breath test at screening and Day -1.&#xD;
&#xD;
         11. No personal history (or current) or hereditary hearing loss, persistent tinnitus,&#xD;
             persistent vertigo, persistent imbalance, and persistent unsteadiness.&#xD;
&#xD;
         12. Body Mass Index (BMI) of 19.0 to 30.0 kg/m2 (inclusive); and a total body weight &gt;50.0&#xD;
             kg (110 lbs) and &lt;100.0 kg.&#xD;
&#xD;
        Subjects with any of the following characteristics/conditions will not be included in the&#xD;
        study:&#xD;
&#xD;
          1. Subjects who are investigational site staff members directly involved in the conduct&#xD;
             of the study and their family members, site staff members otherwise supervised by the&#xD;
             Investigator, or subjects who are the Sponsor employees directly involved in the&#xD;
             conduct of the study.&#xD;
&#xD;
          2. Concurrent participation or participation in another clinical trial within at least 5&#xD;
             tissue half-lives prior to dosing (calculated from the previous study's last dosing&#xD;
             day). If the previous trial involved agents with delayed effects or prolonged&#xD;
             metabolism, a 12 months interval is required.&#xD;
&#xD;
          3. Evidence or history of clinically relevant hematological, renal, endocrine, pulmonary,&#xD;
             gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic&#xD;
             disease (including drug allergies). This includes any acute or chronic medical or&#xD;
             psychiatric condition or laboratory abnormality that may increase the risk associated&#xD;
             with study participation or investigational drug administration or may interfere with&#xD;
             the interpretation of study results and, in the judgment of the Investigator, would&#xD;
             make the subject inappropriate for entry into this study.&#xD;
&#xD;
          4. Presence of mitochondrial mutations making subject susceptible to aminoglycoside&#xD;
             toxicity (A1555G, C1494T, T1095C, A827G, 1-BP DEL, 961T, C INS).&#xD;
&#xD;
          5. Subjects with any history of ear disease or surgeries, persistent dizziness or&#xD;
             persistent tinnitus.&#xD;
&#xD;
          6. Subjects with any abnormality at screening, that indicates the presence of a&#xD;
             vestibular pathology, conductive hearing loss or balance problem (by an ENT).&#xD;
&#xD;
             Subjects with abnormalities in audiometry results at screening as follows: any pure&#xD;
             tone threshold &gt;55 dB and inter-ear difference in any frequency of &gt;20 dB.&#xD;
&#xD;
             Dizziness Handicap Inventory (DHI)-H score&gt;16. Tinnitus Handicap Inventory (THI) H&#xD;
             score &gt;14.&#xD;
&#xD;
          7. History of regular alcohol consumption exceeding 14 drinks/week for females or 21&#xD;
             drinks/week for males (1 drink = 150 mL of wine or 360 mL of beer or 45 mL of hard&#xD;
             liquor) within 6 months of screening.&#xD;
&#xD;
          8. Screening supine blood pressure (BP) ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic),&#xD;
             following at least 5 min of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg&#xD;
             (diastolic), the BP should be repeated two more times and the average of the three BP&#xD;
             values should be used to determine the subject's eligibility.&#xD;
&#xD;
          9. Screening supine 12-lead ECG demonstrating QTc &gt;450 msec for men and &gt;470 msec for&#xD;
             women, or a QRS interval &gt;120 msec. If QTc or QRS exceed these limits, the ECG should&#xD;
             be repeated two more times and the average of the three QTc or QRS values should be&#xD;
             used to determine the subject's eligibility.&#xD;
&#xD;
         10. Subjects with ANY abnormalities in clinical laboratory tests at screening, considered&#xD;
             by the study physician as clinically relevant. In particular, subjects with alanine&#xD;
             aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine and total&#xD;
             bilirubin ≥1.5 upper limit of normal will be excluded.&#xD;
&#xD;
         11. Pregnant or breastfeeding female subjects.&#xD;
&#xD;
         12. Subjects who donated blood or received blood or plasma derivatives in the three months&#xD;
             preceding study drug administration.&#xD;
&#xD;
         13. Unwilling or unable to comply with all scheduled visits, treatment plan, laboratory&#xD;
             tests and other study procedures and the restrictions described in this protocol.&#xD;
&#xD;
         14. Known relevant allergy to any drug and/or aminoglycosides.&#xD;
&#xD;
         15. Subjects with an inability to communicate well with the Investigators and CPU staff&#xD;
             (e.g., language problem, poor mental development).&#xD;
&#xD;
         16. Subjects with visual impairment or inability to read and comprehend the DHI and THI&#xD;
             scales.&#xD;
&#xD;
         17. Subjects with any acute medical situation (e.g., acute infection) within 48 hours of&#xD;
             study start, which is considered of significance by the Investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>SGS Life Sciences, Clinical Pharmacology Unit</name>
      <address>
        <city>Antwerp</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <link>
    <url>http://www.eloxxpharma.com</url>
    <description>Eloxx Pharmaceuticals Website</description>
  </link>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>August 30, 2017</study_first_submitted>
  <study_first_submitted_qc>September 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>August 17, 2023</last_update_submitted>
  <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Translational read through</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Genetic Diseases, Inborn</mesh_term>
  </condition_browse>
  <!-- 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/NCT03292302
org study id: EL-006
nct id: NCT03292302
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Phase 1 Single Ascending Dose Study in Normal Healthy Volunteers
This is a study in humans of ELX-02, an advanced synthetic aminoglycoside optimized as a
      translational read-through drug (TRID) for the treatment of genetic conditions caused by
      nonsense mutations. This is a classical Phase 1a study designed as a randomized,
      double-blinded, placebo-controlled, single dose escalation to evaluate the safety,
      tolerability and pharmacokinetics of ELX-02 in healthy adult volunteers.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Adverse Events
time frame: 0-10 days
description: Incidence and characteristics of adverse events occurring following single doses of ELX-02
measure: Pharmacokinetics: Maximum plasma concentration (Cmax)
time frame: 0-10 days
description: Cmax will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.
measure: Pharmacokinetics: Time at which Cmax occurs (tmax)
time frame: 0-10 days
description: tmax will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.
measure: Pharmacokinetics: Area under the plasma concentration-time curve calculated from time of administration to time 24h (AUC24h)
time frame: 0-10 days
description: AUC24h will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.
measure: Pharmacokinetics: Area under the plasma concentration-time curve calculated from time of administration to time 48h (AUC48h)
time frame: 0-10 days
description: AUC48h will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.
measure: Pharmacokinetics: Area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf)
time frame: 0-10 days
description: AUCinf will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.
measure: Pharmacokinetics: Mean residence time (MRT)
time frame: 0-10 days
description: MRT will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.
measure: Pharmacokinetics: Elimination half-life (t1/2)
time frame: 0-10 days
description: t1/2 will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.
measure: Pharmacokinetics: Volume of distribution (Vd/F)
time frame: 0-10 days
description: Vd/F will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.
measure: Pharmacokinetics: Clearance (CL/F)
time frame: 0-10 days
description: CL/F will be determined for ELX-02 and an estimation of ELX-02 dose proportionality of PK parameters.
arm group label: Placebo Comparator Arm
arm group type: Placebo Comparator
description: Placebo
arm group label: Active treatment
arm group type: Active Comparator
description: ELX-02
intervention type: Drug
intervention name: Placebo
description: Placebo comparator
arm group label: Placebo Comparator Arm
intervention type: Drug
intervention name: ELX-02
description: Synthetic aminoglycoside
arm group label: Active treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Belgium
url: http://www.eloxxpharma.com
description: Eloxx Pharmaceuticals Website
responsible party type: Sponsor
mesh term: Genetic Diseases, Inborn