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A Study of GMA301 in Subjects With Pulmonary Arterial Hypertension

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ClinicalTrials.gov Identifier: NCT04503733
Recruitment Status : Recruiting
First Posted : August 7, 2020
Last Update Posted : January 14, 2022
Sponsor:
Information provided by (Responsible Party):
Gmax Biopharm LLC.

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

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension 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 Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : October 22, 2020
Estimated Primary Completion Date : October 26, 2022
Estimated Study Completion Date : June 10, 2023


Arm Intervention/treatment
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

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

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

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

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.




Primary Outcome Measures :
  1. 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 Measures :
  1. 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) ]
  2. 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 ]
  3. Comparing 6MWT distance [ Time Frame: Baseline to Week 12 ]

Other Outcome Measures:
  1. Changes in REVEAL 2.0 risk score at Week 12 compared with baseline [ Time Frame: Baseline to Week 12 ]
    Calculated risk scores can range from 0 (lowest risk) to 23 (highest risk).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04503733


Contacts
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Contact: Jianjun Wu +8618358737112 jianjunwu@gmaxbiopharm.com

Locations
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United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Aaron Waxman         
China
Peking Union Medical College Hospital - Dongcheng District Recruiting
Beijing, China
Contact: Zhicheng Jing         
Xiangya Hospital, Central South University Recruiting
Changsha, China
Contact: Zaixin Yu         
The First Affiliated Hospital of Chongqing Medical University Recruiting
Chongqing, China
Contact: Wei Huang         
Guangdong General Hospital Recruiting
Guangzhou, China
Contact: Hua Yao         
Shanghai Pulmonary Hospital Recruiting
Shanghai, China
Contact: Lan Wang         
The First Affiliated Hospital of Xi'an Jiaotong University Recruiting
Xian, China
Contact: Fenling Fan         
Sponsors and Collaborators
Gmax Biopharm LLC.
Investigators
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Principal Investigator: Hua Yao Guangdong Provincial People's Hospital
Principal Investigator: Lan Wang Shanghai Pulmonary Hospital, Shanghai, China
Principal Investigator: Wei Huang First Affiliated Hospital of Chongqing Medical University
Principal Investigator: Zaixin Yu Xiangya Hospital of Central South University
Principal Investigator: Fenling Fan First Affiliated Hospital Xi'an Jiaotong University
Principal Investigator: Zhicheng Jing Peking Union Medical College Hospital - Dongcheng District
Principal Investigator: Aaron Waxman Brigham and Women's Hospital
  Study Documents (Full-Text)

Documents provided by Gmax Biopharm LLC.:
Informed Consent Form  [PDF] April 2, 2020

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Responsible Party: Gmax Biopharm LLC.
ClinicalTrials.gov Identifier: NCT04503733    
Other Study ID Numbers: GETA_MAD_01
First Posted: August 7, 2020    Key Record Dates
Last Update Posted: January 14, 2022
Last Verified: December 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pulmonary Arterial Hypertension
Familial Primary Pulmonary Hypertension
Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases