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A Study of GMA301 in Subjects With Pulmonary Arterial Hypertension

Primary Purpose

Pulmonary Arterial Hypertension

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Q4W GMA301 IV injections (300 mg)
Q4W GMA301 IV injections (600 mg)
Q4W GMA301 IV injections (1000 mg)
Q4W GMA301 IV injections (1800 mg)
Q4W placebo IV injections
Sponsored by
Gmax Biopharm LLC.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

Subjects must meet all of the following criteria:

  1. Male or female, aged 18 to 75 years inclusive
  2. WHO Group 1 PAH related to one of the following conditions:

    1. Idiopathic
    2. Heritable
    3. Drugs or toxins-induced
    4. Associated with connective tissue disease
    5. Associated with congenital heart disease if subjects underwent surgical correction more than 12 months before Screening
  3. Symptoms due to PAH are consistent with WHO functional class II- III
  4. Have not taken endothelin receptor antagonists (ERAs) within 3 months before Randomization
  5. Has been taking at least one oral PAH targeted drug that has been approved by local guidelines for at least 3 months before Screening with stable dosage and the disease did not worsen during this period per Investigator's judgment
  6. Right heart catheterization (RHC) result meets below criteria when Screening:

    1. Mean pulmonary arterial pressure (PAP) ≥25 mmHg
    2. Pulmonary vascular resistance (PVR) >3 Woods units
    3. PA wedge pressure (PAWP) ≤15 mmHg

    If a subject has undergone RHC within 3 months before Screening, the waveform results will serve as baseline data only if they meet the entry criteria and the RHC at Screening will not be repeated. In case PAWP cannot be well measured during RHC, left ventricular end diastolic pressure will be tested by left heart catheterization.

  7. Has a six-minute walk test (6MWT) with distance between 150 to 450 meters at Screening
  8. The dosage of digitalis drugs or L-arginine supplementation must be stable for at least 1 month before Screening, if applicable.
  9. No new use of an IV diuretic, cardiotonic (positive inotropic agents), or vasoactive drug within 30 days before Screening
  10. Both male and female subjects agree to use 2 medically acceptable methods of contraception (Appendix 4) throughout the entire study period from informed consent signing to 90 days after last dose, if the possibility of conception exists. Medically acceptable methods of contraception include oral, implantable, or injectable contraceptives (starting 2 months before dosing); diaphragm with vaginal spermicide; intrauterine device; condom and partner using vaginal spermicide; and surgical sterilization (6 months after surgery). Women who are surgically sterile or those who are postmenopausal for at least 2 years are not considered to be of childbearing potential. Eligible male and female subjects must agree not to participate in a conception process (i.e. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) during the study and for 90 days after the last dose of study drug.
  11. Body weight no less than 40 kg at Screening
  12. Able to understand and willing to sign the Informed Consent Form (ICF) and comply with the study procedures.

Exclusion Criteria

Subjects who me et any of the following criteria will not be allowed to participate in this study:

  1. Diagnosed with WHO Group II, III, IV, V of PH
  2. Use of calcium channel blockers within 1 month prior to Screening
  3. Systolic blood pressure (SBP) >160 mmHg or diastolic blood pressure (DBP) >100 mmHg at Screening
  4. SBP <90 mmHg at Screening
  5. Pulmonary function test: FEV1 <60% of predicted, TLC <60% of predicted, DLCO <60% of predicted
  6. History of pulmonary embolism as judged by the Investigator
  7. Uncontrolled sleep apnea at the discretion of the Investigator
  8. Limited full participation in the 6MWT due to arthritic, neuromuscular, vascular or other diseases unrelated to PAH
  9. History of acute cardiovascular and/or cerebrovascular events within 6 months before Screening
  10. Echocardiogram (ECHO) demonstrating at least one of the following at Screening:

    1. LVEF <50%
    2. Mean end-diastolic left ventricular septal and posterior wall thickness of >12 mm
    3. Left atrial (LA) area on apical 4 chamber view >20 cm2
    4. LA volume >55 mL
    5. LA volume index >34 mL/m2
    6. Significant valvular heart disease including moderate or severe mitral or aortic stenosis with an aortic valve area <1.0 cm2 or mitral valve area <1.5 cm2, greater than moderate aortic or mitral regurgitation, greater than moderate tricuspid or pulmonic stenosis
  11. Restrictive, dilated or hypertrophic cardiomyopathy or constrictive pericarditis
  12. Using non-oral prostacyclin when Screening
  13. Laboratory parameters during Screening:

    1. Baseline aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2 times the upper limit of normal (ULN) or total bilirubin ≥1.5 times ULN
    2. Estimated glomerular filtration rate (eGFR) <60 mL/min by Cockcroft-Gault formula

      Online calculation available from https://www.kidney.org/professionals/KDOQI/gfr_calculatorCoc

      Cockcroft-Gault formula (1973):

      Male: CCr=((l40-Age) × Weight)/(72×SCr)

      Female: CCr={((l40-Age) × Weight)/(72×SCr)}× 0.85

      CCr (creatinine clearance rate) = mL/min

      Age = year

      Weight = Kg

      SCr (serum creatinine) = mg/dL

    3. Hemoglobin concentration ≤100 g/L at Screening
  14. QTc interval by Fridericia's criteria (QTcF) ≥500 msec at Screening
  15. Malignancy within 5 years before Screening visit (with the exception of localized non-metastatic basal cell carcinoma of the skin, non-metastatic carcinoma of the prostate or in-situ carcinoma of the cervix excised with curative results)
  16. Alcohol or drug abuse within 1 year before Screening
  17. A psychiatric, addictive or other disorder that compromises the ability to give informed consent for participating in this study
  18. History of organ transplantation
  19. Pregnant or nursing females
  20. History of HIV
  21. Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), or HIV antibody (HIV-ab)
  22. Enrolled in another interventional study within 30 days before Screening
  23. Any condition that, in the opinion of the Investigator, prevents a potential subject from safely participating in the study
  24. Start a new exercise program or participate in any unusually strenuous physical exertion within 6 weeks prior to Screening.

Sites / Locations

  • Brigham and Women's HospitalRecruiting
  • Peking Union Medical College Hospital - Dongcheng DistrictRecruiting
  • Xiangya Hospital, Central South UniversityRecruiting
  • The First Affiliated Hospital of Chongqing Medical UniversityRecruiting
  • Guangdong General HospitalRecruiting
  • Shanghai Pulmonary HospitalRecruiting
  • The First Affiliated Hospital of Xi'an Jiaotong UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Q4W GMA301 IV injections (300 mg)

Q4W GMA301 IV injections (600 mg)

Q4W GMA301 IV injections (1000 mg)

Q4W GMA301 IV injections (1800 mg)

Arm Description

Drug: Q4W GMA301 IV injections (300 mg) Each cohort will contain 12 subjects, 9 of whom will be administered active GMA301 and 3 of whom will be administrated placebo. Other: Q4W placebo IV injections Placebo is indistinguishable from GMA301

Drug: Q4W GMA301 IV injections (600 mg) Each cohort will contain 12 subjects, 9 of whom will be administered active GMA301 and 3 of whom will be administrated placebo. Other: Q4W placebo IV injections Placebo is indistinguishable from GMA301

Drug: Q4W GMA301 IV injections (1000 mg) Each cohort will contain 12 subjects, 9 of whom will be administered active GMA301 and 3 of whom will be administrated placebo. Other: Q4W placebo IV injections Placebo is indistinguishable from GMA301

Drug: Q4W GMA301 IV injections (1800 mg) Each cohort will contain 12 subjects, 9 of whom will be administered active GMA301 and 3 of whom will be administrated placebo. Other: Q4W placebo IV injections Placebo is indistinguishable from GMA301

Outcomes

Primary Outcome Measures

The incidence of Treatment-emergent Adverse Events (TEAE) in subjects assigned to GMA301 compared with those assigned to placebo.

Secondary Outcome Measures

Pharmacokinetics (Area under the serum concentration- time curve from time zero to the last measurable concentration)
Comparison of GMA301 treatment effect at Week 12 versus baseline regarding the pulmonary vascular resistance (PVR) based on right heart catheterization (RHC)
Comparing 6MWT distance

Full Information

First Posted
July 24, 2020
Last Updated
December 29, 2021
Sponsor
Gmax Biopharm LLC.
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1. Study Identification

Unique Protocol Identification Number
NCT04503733
Brief Title
A Study of GMA301 in Subjects With Pulmonary Arterial Hypertension
Official Title
A Randomized, Double-blind, Placebo-Controlled, Dose Escalation Study to Assess Safety, Efficacy and Pharmacokinetics of GMA301 in Subjects With Pulmonary Arterial Hypertension
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Recruiting
Study Start Date
October 22, 2020 (Actual)
Primary Completion Date
October 26, 2022 (Anticipated)
Study Completion Date
June 10, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gmax Biopharm LLC.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
A Randomized, Placebo-Controlled, Double-blind, Dose Escalation Study to Assess Safety, Efficacy and Pharmacokinetics of GMA301 Injection in Subjects with Pulmonary Arterial Hypertension
Detailed Description
Drug: Q4W GMA301 IV injections (300 mg) Drug: Q4W GMA301 IV injections (600 mg) Drug: Q4W GMA301 IV injections (1000 mg) Drug: Q4W GMA301 IV injections (1800 mg) Other: Q4W placebo IV injections

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Q4W GMA301 IV injections (300 mg)
Arm Type
Experimental
Arm Description
Drug: Q4W GMA301 IV injections (300 mg) Each cohort will contain 12 subjects, 9 of whom will be administered active GMA301 and 3 of whom will be administrated placebo. Other: Q4W placebo IV injections Placebo is indistinguishable from GMA301
Arm Title
Q4W GMA301 IV injections (600 mg)
Arm Type
Experimental
Arm Description
Drug: Q4W GMA301 IV injections (600 mg) Each cohort will contain 12 subjects, 9 of whom will be administered active GMA301 and 3 of whom will be administrated placebo. Other: Q4W placebo IV injections Placebo is indistinguishable from GMA301
Arm Title
Q4W GMA301 IV injections (1000 mg)
Arm Type
Experimental
Arm Description
Drug: Q4W GMA301 IV injections (1000 mg) Each cohort will contain 12 subjects, 9 of whom will be administered active GMA301 and 3 of whom will be administrated placebo. Other: Q4W placebo IV injections Placebo is indistinguishable from GMA301
Arm Title
Q4W GMA301 IV injections (1800 mg)
Arm Type
Experimental
Arm Description
Drug: Q4W GMA301 IV injections (1800 mg) Each cohort will contain 12 subjects, 9 of whom will be administered active GMA301 and 3 of whom will be administrated placebo. Other: Q4W placebo IV injections Placebo is indistinguishable from GMA301
Intervention Type
Drug
Intervention Name(s)
Q4W GMA301 IV injections (300 mg)
Intervention Description
Each cohort will contain 12 subjects, 9 of whom will be administered active GMA301 and 3 of whom will be administrated placebo.
Intervention Type
Drug
Intervention Name(s)
Q4W GMA301 IV injections (600 mg)
Intervention Description
Each cohort will contain 12 subjects, 9 of whom will be administered active GMA301 and 3 of whom will be administrated placebo.
Intervention Type
Drug
Intervention Name(s)
Q4W GMA301 IV injections (1000 mg)
Intervention Description
Each cohort will contain 12 subjects, 9 of whom will be administered active GMA301 and 3 of whom will be administrated placebo.
Intervention Type
Drug
Intervention Name(s)
Q4W GMA301 IV injections (1800 mg)
Intervention Description
Each cohort will contain 12 subjects, 9 of whom will be administered active GMA301 and 3 of whom will be administrated placebo.
Intervention Type
Other
Intervention Name(s)
Q4W placebo IV injections
Intervention Description
Placebo is indistinguishable from GMA301.
Primary Outcome Measure Information:
Title
The incidence of Treatment-emergent Adverse Events (TEAE) in subjects assigned to GMA301 compared with those assigned to placebo.
Time Frame
Through study completion (up to 22 weeks)
Secondary Outcome Measure Information:
Title
Pharmacokinetics (Area under the serum concentration- time curve from time zero to the last measurable concentration)
Time Frame
Through study completion (up to 22 weeks)
Title
Comparison of GMA301 treatment effect at Week 12 versus baseline regarding the pulmonary vascular resistance (PVR) based on right heart catheterization (RHC)
Time Frame
Baseline to Week 12
Title
Comparing 6MWT distance
Time Frame
Baseline to Week 12
Other Pre-specified Outcome Measures:
Title
Changes in REVEAL 2.0 risk score at Week 12 compared with baseline
Description
Calculated risk scores can range from 0 (lowest risk) to 23 (highest risk).
Time Frame
Baseline to Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Subjects must meet all of the following criteria: Male or female, aged 18 to 75 years inclusive WHO Group 1 PAH related to one of the following conditions: Idiopathic Heritable Drugs or toxins-induced Associated with connective tissue disease Associated with congenital heart disease if subjects underwent surgical correction more than 12 months before Screening Symptoms due to PAH are consistent with WHO functional class II- III Have not taken endothelin receptor antagonists (ERAs) within 3 months before Randomization Has been taking at least one oral PAH targeted drug that has been approved by local guidelines for at least 3 months before Screening with stable dosage and the disease did not worsen during this period per Investigator's judgment Right heart catheterization (RHC) result meets below criteria when Screening: Mean pulmonary arterial pressure (PAP) ≥25 mmHg Pulmonary vascular resistance (PVR) >3 Woods units PA wedge pressure (PAWP) ≤15 mmHg If a subject has undergone RHC within 3 months before Screening, the waveform results will serve as baseline data only if they meet the entry criteria and the RHC at Screening will not be repeated. In case PAWP cannot be well measured during RHC, left ventricular end diastolic pressure will be tested by left heart catheterization. Has a six-minute walk test (6MWT) with distance between 150 to 450 meters at Screening The dosage of digitalis drugs or L-arginine supplementation must be stable for at least 1 month before Screening, if applicable. No new use of an IV diuretic, cardiotonic (positive inotropic agents), or vasoactive drug within 30 days before Screening Both male and female subjects agree to use 2 medically acceptable methods of contraception (Appendix 4) throughout the entire study period from informed consent signing to 90 days after last dose, if the possibility of conception exists. Medically acceptable methods of contraception include oral, implantable, or injectable contraceptives (starting 2 months before dosing); diaphragm with vaginal spermicide; intrauterine device; condom and partner using vaginal spermicide; and surgical sterilization (6 months after surgery). Women who are surgically sterile or those who are postmenopausal for at least 2 years are not considered to be of childbearing potential. Eligible male and female subjects must agree not to participate in a conception process (i.e. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) during the study and for 90 days after the last dose of study drug. Body weight no less than 40 kg at Screening Able to understand and willing to sign the Informed Consent Form (ICF) and comply with the study procedures. Exclusion Criteria Subjects who me et any of the following criteria will not be allowed to participate in this study: Diagnosed with WHO Group II, III, IV, V of PH Use of calcium channel blockers within 1 month prior to Screening Systolic blood pressure (SBP) >160 mmHg or diastolic blood pressure (DBP) >100 mmHg at Screening SBP <90 mmHg at Screening Pulmonary function test: FEV1 <60% of predicted, TLC <60% of predicted, DLCO <60% of predicted History of pulmonary embolism as judged by the Investigator Uncontrolled sleep apnea at the discretion of the Investigator Limited full participation in the 6MWT due to arthritic, neuromuscular, vascular or other diseases unrelated to PAH History of acute cardiovascular and/or cerebrovascular events within 6 months before Screening Echocardiogram (ECHO) demonstrating at least one of the following at Screening: LVEF <50% Mean end-diastolic left ventricular septal and posterior wall thickness of >12 mm Left atrial (LA) area on apical 4 chamber view >20 cm2 LA volume >55 mL LA volume index >34 mL/m2 Significant valvular heart disease including moderate or severe mitral or aortic stenosis with an aortic valve area <1.0 cm2 or mitral valve area <1.5 cm2, greater than moderate aortic or mitral regurgitation, greater than moderate tricuspid or pulmonic stenosis Restrictive, dilated or hypertrophic cardiomyopathy or constrictive pericarditis Using non-oral prostacyclin when Screening Laboratory parameters during Screening: Baseline aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2 times the upper limit of normal (ULN) or total bilirubin ≥1.5 times ULN Estimated glomerular filtration rate (eGFR) <60 mL/min by Cockcroft-Gault formula Online calculation available from https://www.kidney.org/professionals/KDOQI/gfr_calculatorCoc Cockcroft-Gault formula (1973): Male: CCr=((l40-Age) × Weight)/(72×SCr) Female: CCr={((l40-Age) × Weight)/(72×SCr)}× 0.85 CCr (creatinine clearance rate) = mL/min Age = year Weight = Kg SCr (serum creatinine) = mg/dL Hemoglobin concentration ≤100 g/L at Screening QTc interval by Fridericia's criteria (QTcF) ≥500 msec at Screening Malignancy within 5 years before Screening visit (with the exception of localized non-metastatic basal cell carcinoma of the skin, non-metastatic carcinoma of the prostate or in-situ carcinoma of the cervix excised with curative results) Alcohol or drug abuse within 1 year before Screening A psychiatric, addictive or other disorder that compromises the ability to give informed consent for participating in this study History of organ transplantation Pregnant or nursing females History of HIV Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), or HIV antibody (HIV-ab) Enrolled in another interventional study within 30 days before Screening Any condition that, in the opinion of the Investigator, prevents a potential subject from safely participating in the study Start a new exercise program or participate in any unusually strenuous physical exertion within 6 weeks prior to Screening.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jianjun Wu
Phone
+8618358737112
Email
jianjunwu@gmaxbiopharm.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hua Yao
Organizational Affiliation
Guangdong Provincial People's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lan Wang
Organizational Affiliation
Shanghai Pulmonary Hospital, Shanghai, China
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Wei Huang
Organizational Affiliation
First Affiliated Hospital of Chongqing Medical University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Zaixin Yu
Organizational Affiliation
Xiangya Hospital of Central South University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Fenling Fan
Organizational Affiliation
First Affiliated Hospital Xi'an Jiaotong University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Zhicheng Jing
Organizational Affiliation
Peking Union Medical College Hospital - Dongcheng District
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Aaron Waxman
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aaron Waxman
Facility Name
Peking Union Medical College Hospital - Dongcheng District
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhicheng Jing
Facility Name
Xiangya Hospital, Central South University
City
Changsha
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zaixin Yu
Facility Name
The First Affiliated Hospital of Chongqing Medical University
City
Chongqing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wei Huang
Facility Name
Guangdong General Hospital
City
Guangzhou
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hua Yao
Facility Name
Shanghai Pulmonary Hospital
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lan Wang
Facility Name
The First Affiliated Hospital of Xi'an Jiaotong University
City
Xian
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fenling Fan

12. IPD Sharing Statement

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A Study of GMA301 in Subjects With Pulmonary Arterial Hypertension

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