<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/NCT04505137</url>
  </required_header>
  <id_info>
    <org_study_id>GETA_SAD_02</org_study_id>
    <nct_id>NCT04505137</nct_id>
  </id_info>
  <brief_title>A Study to Investigate Safe and Tolerable Dose of GMA301 Injection in Healthy Volunteers</brief_title>
  <official_title>A Phase 1, Placebo-Controlled, Double-Blind, Dose-Escalation Study To Investigate The Safety, Tolerability, And Pharmacokinetics Of A Single Intravenous Dose Of GMA301 Injection In Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gmax Biopharm Australia Pty Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Metaclinical</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Syneos Heath</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Gmax Biopharm LLC.</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>
      This study is a single-centre, randomized, double-blind, placebo-controlled, dose escalation&#xD;
      study to assess the safety, tolerability and PK of GMA301 Injection in healthy subjects. Two&#xD;
      sequential dosing cohorts (at ascending dose fashion), each with 6 subjects receiving GMA301&#xD;
      Injection and 2 subjects receiving placebo (total of 16 subjects), will be given single&#xD;
      doses. The doses to be administered in the two cohorts will be 1500 mg and 2000 mg&#xD;
      respectively, or matching placebo&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The current study is an extension of the previous study #1010218 (ACTRN12618000121268) to&#xD;
      further explore the safety and PK profile of GMA301 injection at higher dosage. The SRC&#xD;
      (Safety Review Committee) will be responsible for the assessment of safety, tolerability, and&#xD;
      PK data for each dose level and to make decisions with regards to study progression. A&#xD;
      Statistical Analysis Plan (SAP) will be written after finalizing the protocol and prior to&#xD;
      database lock. The SAP will detail the implementation of all the planned statistical analyses&#xD;
      in accordance with the principal features stated in the protocol. Adverse events will be&#xD;
      coded using the Medical Dictionary for Regulatory Activities (MedDRA).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2, 2020</start_date>
  <completion_date type="Actual">March 19, 2021</completion_date>
  <primary_completion_date type="Actual">March 19, 2021</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>Two sequential dosing cohorts, each with 6 subjects receiving GMA301 Injection and 2 subjects receiving placebo (total of 16 subjects). The doses to be administered will be 1500 mg and 2000 mg, or matching placebo, single dosing. Each cohort will include at least 2 participants of Chinese descent, if possible.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>The subjects and the clinical personnel involved in the collection, monitoring, revision, or evaluation of AEs, or personnel who could have an impact on the outcome of the study will be blinded with respect to the subject's treatment assignment (GMA301 Injection or placebo). Blinding will be maintained at least until the clinical phase of the study is completed (i.e., when reporting and evaluation of all AEs have been completed, for all cohorts).</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and Tolerability</measure>
    <time_frame>All AEs (adverse events) will be captured from the time the investigator received the signed ICF (informed consent form) of subjects until study completion ie Day 70</time_frame>
    <description>To assess the safety and tolerability of GMA301 Injection following single escalating intravenous (IV) injections in healthy subjects.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Profile</measure>
    <time_frame>Blood PK samples will be collected for analysis during the treatment period at: pre-dose and 4 hours, 8 hours, 24 hours, 72 hours, 168 hours post-dose (Day 7), Day 14, Day 21, Day 28, Day 42, Day 56 and Day 70</time_frame>
    <description>PK parameters determined is AUC(0-inf)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Profile</measure>
    <time_frame>Blood PK samples will be collected for analysis during the treatment period at: pre-dose and 4 hours, 8 hours, 24 hours, 72 hours, 168 hours post-dose (Day 7), Day 14, Day 21, Day 28, Day 42, Day 56 and Day 70</time_frame>
    <description>PK parameters determined is AUC(0-t)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Profile</measure>
    <time_frame>Blood PK samples will be collected for analysis during the treatment period at: pre-dose and 4 hours, 8 hours, 24 hours, 72 hours, 168 hours post-dose (Day 7), Day 14, Day 21, Day 28, Day 42, Day 56 and Day 70</time_frame>
    <description>PK parameters determined is C(max)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Profile</measure>
    <time_frame>Blood PK samples will be collected for analysis during the treatment period at: pre-dose and 4 hours, 8 hours, 24 hours, 72 hours, 168 hours post-dose (Day 7), Day 14, Day 21, Day 28, Day 42, Day 56 and Day 70</time_frame>
    <description>PK parameters determined is residual area</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Profile</measure>
    <time_frame>Blood PK samples will be collected for analysis during the treatment period at: pre-dose and 4 hours, 8 hours, 24 hours, 72 hours, 168 hours post-dose (Day 7), Day 14, Day 21, Day 28, Day 42, Day 56 and Day 70</time_frame>
    <description>PK parameters determined is T(max)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Profile</measure>
    <time_frame>Blood PK samples will be collected for analysis during the treatment period at: pre-dose and 4 hours, 8 hours, 24 hours, 72 hours, 168 hours post-dose (Day 7), Day 14, Day 21, Day 28, Day 42, Day 56 and Day 70</time_frame>
    <description>PK parameters determined is T(1/2 el)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Profile</measure>
    <time_frame>Blood PK samples will be collected for analysis during the treatment period at: pre-dose and 4 hours, 8 hours, 24 hours, 72 hours, 168 hours post-dose (Day 7), Day 14, Day 21, Day 28, Day 42, Day 56 and Day 70</time_frame>
    <description>PK parameters determined is K(el)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose for GMA301 Injection for subsequent clinical studies</measure>
    <time_frame>All AEs will be captured from the time the investigator received the signed ICF of subjects until study completion ie Day 70</time_frame>
    <description>To identify appropriate doses of GMA301 Injection for subsequent clinical studies</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Pulmonary Arterial Hypertension</condition>
  <arm_group>
    <arm_group_label>GMA301 1500mg Or Placebo Injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two sentinel subjects (1 active and 1 placebo) will be dosed first and then reaming 6 subjects will dosed within 7 days. The dose to be administered is 1500 mg single Intravenous dose of GMA301 Injection.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GMA301 2000mg Or Placebo Injection</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Two sentinel subjects (1 active and 1 placebo) will be dosed first and then reaming 6 subjects will dosed within 7 days. The dose to be administered is 2000 mg single intravenous dose of GMA301 Injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GMA301 Injection</intervention_name>
    <description>GMA301 Injection administered as a single dose of 1500 mg</description>
    <arm_group_label>GMA301 1500mg Or Placebo Injection</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>GMA301 Placebo Injection</intervention_name>
    <description>GMA301 Injection without GMA301 administered as a single intravenous dose</description>
    <arm_group_label>GMA301 1500mg Or Placebo Injection</arm_group_label>
    <arm_group_label>GMA301 2000mg Or Placebo Injection</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GMA301 Injection</intervention_name>
    <description>GMA301 Injection administered as a single dose of 2000 mg</description>
    <arm_group_label>GMA301 2000mg Or Placebo Injection</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Non-smoker (no use of tobacco or nicotine products within 2 months prior to screening)&#xD;
             with BMI &gt; 18.5 and &lt; 30.0 kg/m2 and body weight ≥ 50.0 kg for males and ≥ 45.0 kg for&#xD;
             females. Each cohort will include at least 2 participants of Chinese descent, if&#xD;
             possible.&#xD;
&#xD;
          2. Healthy as defined by:&#xD;
&#xD;
               1. The absence of clinically significant illness and surgery within 4 weeks prior to&#xD;
                  dosing.&#xD;
&#xD;
               2. The absence of clinically significant history of neurological, endocrine,&#xD;
                  cardiovascular, respiratory, hematological, immunological, psychiatric,&#xD;
                  gastrointestinal, renal, hepatic, and metabolic disease.&#xD;
&#xD;
          3. Females of childbearing potential who are sexually active with a male partner must be&#xD;
             willing to use one of the following acceptable contraceptive methods throughout the&#xD;
             study and for 6 months after the last study drug administration:&#xD;
&#xD;
               1. Oral, injected, or implanted hormonal methods of contraception in combination&#xD;
                  with a barrier method;&#xD;
&#xD;
               2. Placement of an intrauterine device (IUD) or intrauterine system (IUS) in&#xD;
                  combination with a barrier method;&#xD;
&#xD;
               3. Sterilized male partner (with the appropriate post-vasectomy documentation of the&#xD;
                  absence of sperm in the ejaculate) in combination with a barrier method;&#xD;
&#xD;
               4. True abstinence, when this is in line with the subject's preferred and usual&#xD;
                  lifestyle.&#xD;
&#xD;
          4. Male subjects must agree to avoid causing pregnancy by using a reliable method of&#xD;
             birth control during the study and for 6 months after study drug administration and&#xD;
             must be willing to use one of the following acceptable contraceptives:&#xD;
&#xD;
               1. Simultaneous use of a male condom and, for the female partner, hormonal&#xD;
                  contraceptives used since at least 4 weeks or intra-uterine contraceptive device&#xD;
                  placed since at least 4 weeks;&#xD;
&#xD;
               2. Simultaneous use of a male condom and, for the female partner, a diaphragm or&#xD;
                  cervical cap.&#xD;
&#xD;
          5. Male subjects (including men who have had a vasectomy) with a pregnant partner must&#xD;
             agree to use a condom from the first study drug administration until at least 6 months&#xD;
             after study drug administration.&#xD;
&#xD;
          6. Male subjects must be willing not to donate sperm during the study and for 6 months&#xD;
             following study drug administration.&#xD;
&#xD;
          7. Capable of consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any clinically significant abnormality at physical examination, clinically significant&#xD;
             abnormal laboratory test results or positive test for HIV, hepatitis B, or hepatitis C&#xD;
             found during medical screening.&#xD;
&#xD;
          2. Presence or history of any clinically significant chronic condition of the&#xD;
             neurological, respiratory, cardiovascular, gastrointestinal, urogenital, reproductive,&#xD;
             musculoskeletal, endocrine system or cancer.&#xD;
&#xD;
          3. Clinically significant (as judged by the investigator) presence of acute illness&#xD;
             (e.g., gastrointestinal illness, infection such as influenza, upper respiratory tract&#xD;
             infection) upo admission to the study site.&#xD;
&#xD;
          4. Alanine aminotransferase and/or aspartate aminotransferase above the upper limit of&#xD;
             normal.&#xD;
&#xD;
          5. Positive urine drug screen or alcohol breath test at screening.&#xD;
&#xD;
          6. Positive pregnancy test at screening.&#xD;
&#xD;
          7. Clinically significant ECG abnormalities or vital sign abnormalities (systolic blood&#xD;
             pressure lower than 90 or over 140 mmHg, diastolic blood pressure lower than 60 or&#xD;
             over 90 mmHg,or heart rate less than 40 or over 100 bpm) at screening. Up to 2&#xD;
             additional measurements may be taken after an appropriate resting interval (at least&#xD;
             10 minutes) at Screening to confirm eligibility.&#xD;
&#xD;
          8. History of type 1 hypersensitivity or severe cutaneous adverse reaction to any&#xD;
             medication, or to any excipient in the formulation, or history of significant atopy.&#xD;
&#xD;
          9. Hemoglobin below lower limit of normal.&#xD;
&#xD;
         10. Women who intend to become pregnant or are lactating.&#xD;
&#xD;
         11. History of significant alcohol abuse within 1 year prior to screening or regular use&#xD;
             of alcohol within 6 months prior to the screening visit (average weekly alcohol intake&#xD;
             that exceeds 14 units per week (males) or 7 units (females) per week, or are unwilling&#xD;
             to stop alcohol consumption for 24 hours prior to study drug dosing until the&#xD;
             completion of the study (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine;1.5&#xD;
             oz or 45 mL of distilled spirits).&#xD;
&#xD;
         12. History of significant drug abuse within 1 year prior to screening or use of soft&#xD;
             drugs (such as marijuana) within 3 months prior to the screening visit or hard drugs&#xD;
             (such as cocaine, phencyclidine (PCP), crack, opioid derivatives including heroin, and&#xD;
             amphetamine derivatives) within 1 year prior to screening.&#xD;
&#xD;
         13. Participation in a clinical research study involving the administration of an&#xD;
             investigational or marketed drug or device within 30 days prior to dosing,&#xD;
             administration of a biological product in the context of a clinical research study&#xD;
             within 90 days prior to dosing, or concomitant participation in an investigational&#xD;
             study involving no drug or device administration.&#xD;
&#xD;
         14. Use of prescription medications or over-the-counter medications within 7 days prior to&#xD;
             study drug administration, with the exception of simple analgesics such as paracetamol&#xD;
             and routine vitamins.&#xD;
&#xD;
         15. Donated more than 500 mL of blood within 4 weeks prior to study enrollment, or donated&#xD;
             plasma or participated in a plasmapheresis program within 7 days of study drug&#xD;
             administration.&#xD;
&#xD;
         16. Any reason which, in the opinion of the Investigator, would prevent the subject from&#xD;
             participating in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sepehr Shakib, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>CMAX Clinical Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CMAX Clinical Research</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>July 31, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <last_update_submitted>August 30, 2021</last_update_submitted>
  <last_update_submitted_qc>August 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 1, 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>Pulmonary Arterial Hypertension</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04505137
org study id: GETA_SAD_02
nct id: NCT04505137
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is a single-centre, randomized, double-blind, placebo-controlled, dose escalation
      study to assess the safety, tolerability and PK of GMA301 Injection in healthy subjects. Two
      sequential dosing cohorts (at ascending dose fashion), each with 6 subjects receiving GMA301
      Injection and 2 subjects receiving placebo (total of 16 subjects), will be given single
      doses. The doses to be administered in the two cohorts will be 1500 mg and 2000 mg
      respectively, or matching placebo
The current study is an extension of the previous study #1010218 (ACTRN12618000121268) to
      further explore the safety and PK profile of GMA301 injection at higher dosage. The SRC
      (Safety Review Committee) will be responsible for the assessment of safety, tolerability, and
      PK data for each dose level and to make decisions with regards to study progression. A
      Statistical Analysis Plan (SAP) will be written after finalizing the protocol and prior to
      database lock. The SAP will detail the implementation of all the planned statistical analyses
      in accordance with the principal features stated in the protocol. Adverse events will be
      coded using the Medical Dictionary for Regulatory Activities (MedDRA).
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Two sequential dosing cohorts, each with 6 subjects receiving GMA301 Injection and 2 subjects receiving placebo (total of 16 subjects). The doses to be administered will be 1500 mg and 2000 mg, or matching placebo, single dosing. Each cohort will include at least 2 participants of Chinese descent, if possible.
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: The subjects and the clinical personnel involved in the collection, monitoring, revision, or evaluation of AEs, or personnel who could have an impact on the outcome of the study will be blinded with respect to the subject's treatment assignment (GMA301 Injection or placebo). Blinding will be maintained at least until the clinical phase of the study is completed (i.e., when reporting and evaluation of all AEs have been completed, for all cohorts).
measure: Safety and Tolerability
time frame: All AEs (adverse events) will be captured from the time the investigator received the signed ICF (informed consent form) of subjects until study completion ie Day 70
description: To assess the safety and tolerability of GMA301 Injection following single escalating intravenous (IV) injections in healthy subjects.
measure: Pharmacokinetics Profile
time frame: Blood PK samples will be collected for analysis during the treatment period at: pre-dose and 4 hours, 8 hours, 24 hours, 72 hours, 168 hours post-dose (Day 7), Day 14, Day 21, Day 28, Day 42, Day 56 and Day 70
description: PK parameters determined is AUC(0-inf)
measure: Pharmacokinetics Profile
time frame: Blood PK samples will be collected for analysis during the treatment period at: pre-dose and 4 hours, 8 hours, 24 hours, 72 hours, 168 hours post-dose (Day 7), Day 14, Day 21, Day 28, Day 42, Day 56 and Day 70
description: PK parameters determined is AUC(0-t)
measure: Pharmacokinetics Profile
time frame: Blood PK samples will be collected for analysis during the treatment period at: pre-dose and 4 hours, 8 hours, 24 hours, 72 hours, 168 hours post-dose (Day 7), Day 14, Day 21, Day 28, Day 42, Day 56 and Day 70
description: PK parameters determined is C(max)
measure: Pharmacokinetics Profile
time frame: Blood PK samples will be collected for analysis during the treatment period at: pre-dose and 4 hours, 8 hours, 24 hours, 72 hours, 168 hours post-dose (Day 7), Day 14, Day 21, Day 28, Day 42, Day 56 and Day 70
description: PK parameters determined is residual area
measure: Pharmacokinetics Profile
time frame: Blood PK samples will be collected for analysis during the treatment period at: pre-dose and 4 hours, 8 hours, 24 hours, 72 hours, 168 hours post-dose (Day 7), Day 14, Day 21, Day 28, Day 42, Day 56 and Day 70
description: PK parameters determined is T(max)
measure: Pharmacokinetics Profile
time frame: Blood PK samples will be collected for analysis during the treatment period at: pre-dose and 4 hours, 8 hours, 24 hours, 72 hours, 168 hours post-dose (Day 7), Day 14, Day 21, Day 28, Day 42, Day 56 and Day 70
description: PK parameters determined is T(1/2 el)
measure: Pharmacokinetics Profile
time frame: Blood PK samples will be collected for analysis during the treatment period at: pre-dose and 4 hours, 8 hours, 24 hours, 72 hours, 168 hours post-dose (Day 7), Day 14, Day 21, Day 28, Day 42, Day 56 and Day 70
description: PK parameters determined is K(el)
measure: Dose for GMA301 Injection for subsequent clinical studies
time frame: All AEs will be captured from the time the investigator received the signed ICF of subjects until study completion ie Day 70
description: To identify appropriate doses of GMA301 Injection for subsequent clinical studies
arm group label: GMA301 1500mg Or Placebo Injection
arm group type: Experimental
description: Two sentinel subjects (1 active and 1 placebo) will be dosed first and then reaming 6 subjects will dosed within 7 days. The dose to be administered is 1500 mg single Intravenous dose of GMA301 Injection.
arm group label: GMA301 2000mg Or Placebo Injection
arm group type: Experimental
description: Two sentinel subjects (1 active and 1 placebo) will be dosed first and then reaming 6 subjects will dosed within 7 days. The dose to be administered is 2000 mg single intravenous dose of GMA301 Injection.
intervention type: Drug
intervention name: GMA301 Injection
description: GMA301 Injection administered as a single dose of 1500 mg
arm group label: GMA301 1500mg Or Placebo Injection
intervention type: Other
intervention name: GMA301 Placebo Injection
description: GMA301 Injection without GMA301 administered as a single intravenous dose
arm group label: GMA301 1500mg Or Placebo Injection
arm group label: GMA301 2000mg Or Placebo Injection
intervention type: Drug
intervention name: GMA301 Injection
description: GMA301 Injection administered as a single dose of 2000 mg
arm group label: GMA301 2000mg Or Placebo Injection
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sepehr Shakib, Dr
role: Principal Investigator
affiliation: CMAX Clinical Research
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Pulmonary Arterial Hypertension
sharing ipd: No