A Study of GMA301 in Subjects With Pulmonary Arterial Hypertension

Study Purpose

A Randomized, Placebo-Controlled, Double-blind, Dose Escalation Study to Assess Safety, Efficacy and Pharmacokinetics of GMA301 Injection in Subjects with Pulmonary Arterial Hypertension

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 75 Years
Gender All
More Inclusion & Exclusion Criteria

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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04503733
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Gmax Biopharm LLC.
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Hua YaoLan WangWei HuangZaixin YuFenling FanZhicheng JingAaron Waxman
Principal Investigator Affiliation Guangdong Provincial People's HospitalShanghai Pulmonary Hospital, Shanghai, ChinaFirst Affiliated Hospital of Chongqing Medical UniversityXiangya Hospital of Central South UniversityFirst Affiliated Hospital Xi'an Jiaotong UniversityPeking Union Medical College Hospital - Dongcheng DistrictBrigham and Women's Hospital
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries China, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Pulmonary Arterial Hypertension
Additional Details

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

Arms & Interventions

Arms

Experimental: Q4W GMA301 IV injections (300 mg)

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

Experimental: Q4W GMA301 IV injections (600 mg)

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

Experimental: Q4W GMA301 IV injections (1000 mg)

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

Experimental: Q4W GMA301 IV injections (1800 mg)

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

Interventions

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.

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.

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.

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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Brigham and Women's Hospital, Boston, Massachusetts

Status

Recruiting

Address

Brigham and Women's Hospital

Boston, Massachusetts, 02115

Site Contact

Aaron Waxman

jianjunwu@gmaxbiopharm.com

+8618358737112

International Sites

Beijing, China

Status

Recruiting

Address

Peking Union Medical College Hospital - Dongcheng District

Beijing, ,

Site Contact

Zhicheng Jing

jianjunwu@gmaxbiopharm.com

+8618358737112

Changsha, China

Status

Recruiting

Address

Xiangya Hospital, Central South University

Changsha, ,

Chongqing, China

Status

Recruiting

Address

The First Affiliated Hospital of Chongqing Medical University

Chongqing, ,

Guangdong General Hospital, Guangzhou, China

Status

Recruiting

Address

Guangdong General Hospital

Guangzhou, ,

Shanghai Pulmonary Hospital, Shanghai, China

Status

Recruiting

Address

Shanghai Pulmonary Hospital

Shanghai, ,

Xian, China

Status

Recruiting

Address

The First Affiliated Hospital of Xi'an Jiaotong University

Xian, ,

Site Contact

Fenling Fan

jianjunwu@gmaxbiopharm.com

+8618358737112

For more information, please contact PHA at Research@PHAssociation.org and refer to the terms of service below.

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