A Study of GMA301 in Subjects With Pulmonary Arterial Hypertension

NCT ID: NCT04503733

Last Updated: 2022-01-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-22

Study Completion Date

2023-06-10

Brief Summary

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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

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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

Conditions

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Pulmonary Arterial Hypertension

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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

Group Type EXPERIMENTAL

Q4W GMA301 IV injections (300 mg)

Intervention Type DRUG

Each cohort will contain 12 subjects, 9 of whom will be administered active GMA301 and 3 of whom will be administrated placebo.

Q4W placebo IV injections

Intervention Type OTHER

Placebo is indistinguishable from GMA301.

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

Group Type EXPERIMENTAL

Q4W GMA301 IV injections (600 mg)

Intervention Type DRUG

Each cohort will contain 12 subjects, 9 of whom will be administered active GMA301 and 3 of whom will be administrated placebo.

Q4W placebo IV injections

Intervention Type OTHER

Placebo is indistinguishable from GMA301.

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

Group Type EXPERIMENTAL

Q4W GMA301 IV injections (1000 mg)

Intervention Type DRUG

Each cohort will contain 12 subjects, 9 of whom will be administered active GMA301 and 3 of whom will be administrated placebo.

Q4W placebo IV injections

Intervention Type OTHER

Placebo is indistinguishable from GMA301.

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

Group Type EXPERIMENTAL

Q4W GMA301 IV injections (1800 mg)

Intervention Type DRUG

Each cohort will contain 12 subjects, 9 of whom will be administered active GMA301 and 3 of whom will be administrated placebo.

Q4W placebo IV injections

Intervention Type OTHER

Placebo is indistinguishable from GMA301.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Q4W placebo IV injections

Placebo is indistinguishable from GMA301.

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gmax Biopharm LLC.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hua Yao

Role: PRINCIPAL_INVESTIGATOR

Guangdong Provincial People's Hospital

Lan Wang

Role: PRINCIPAL_INVESTIGATOR

Shanghai Pulmonary Hospital, Shanghai, China

Wei Huang

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital of Chongqing Medical University

Zaixin Yu

Role: PRINCIPAL_INVESTIGATOR

Xiangya Hospital of Central South University

Fenling Fan

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital Xi'an Jiaotong University

Zhicheng Jing

Role: PRINCIPAL_INVESTIGATOR

Peking Union Medical College Hospital - Dongcheng District

Aaron Waxman

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

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Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Peking Union Medical College Hospital - Dongcheng District

Beijing, , China

Site Status RECRUITING

Xiangya Hospital, Central South University

Changsha, , China

Site Status RECRUITING

The First Affiliated Hospital of Chongqing Medical University

Chongqing, , China

Site Status RECRUITING

Guangdong General Hospital

Guangzhou, , China

Site Status RECRUITING

Shanghai Pulmonary Hospital

Shanghai, , China

Site Status RECRUITING

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, , China

Site Status RECRUITING

Countries

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United States China

Central Contacts

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Jianjun Wu

Role: CONTACT

+8618358737112

Facility Contacts

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Aaron Waxman

Role: primary

Zhicheng Jing

Role: primary

Zaixin Yu

Role: primary

Wei Huang

Role: primary

Hua Yao

Role: primary

Lan Wang

Role: primary

Fenling Fan

Role: primary

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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GETA_MAD_01

Identifier Type: -

Identifier Source: org_study_id

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