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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 : August 7, 2020
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) Other: Q4W placebo IV injections Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 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 : July 1, 2020
Estimated Primary Completion Date : September 3, 2021
Estimated Study Completion Date : June 10, 2022


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

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




Primary Outcome Measures :
  1. The incidence of Treatment Emergent Adverse Events (TEAE) after the start of GMA301 dosing compared with 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

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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.
  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 if they meet entry criteria; and the RHC at Screening will not be repeated.
  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 or vasoactive drug within 30 days before screening.
  10. Both male and female subjects agree to use a medically acceptable method of contraception 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 meet 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. Using calcium channel blockers when Screening;
  3. BP>160/100mmHg at Screening;
  4. Systolic BP <90 mmHg at Screening;
  5. Pulmonary function test: FEV1<60% of predicted, TLC<60% of predicted, DLCO<60% of predicted;
  6. One of the following tests with confirmed pulmonary embolism and/or chronic thrombo-embolic pulmonary hypertension (CTEPH) following initial diagnosis of PAH:

    1. Pulmonary ventilation/perfusion scan
    2. CT pulmonary angiogram
    3. Contrast dye pulmonary angiogram
  7. History of sleep apnea.
  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:

    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 by biplane modified Simpsons or area-length methods >55 mL
    5. LA volume index >29 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
    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.

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: Jie Li +8618616661528 jieli@gmaxbiopharm.com

Locations
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United States, California
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center Recruiting
Torrance, California, United States, 90502
Contact: Ronald Oudiz         
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Aaron Waxman         
United States, Ohio
The Ohio State University - Dorothy M. Davis Heart and Lung Research Institute Recruiting
Louisville, Ohio, United States, 43210
Contact: Jimmy Shaun Smith         
United States, Texas
The University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Kelly Chin         
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: Jimmy Shaun Smith The Ohio State University - Dorothy M. Davis Heart and Lung Research Institute
Principal Investigator: Aaron Waxman Brigham and Women's Hospital
Principal Investigator: Kelly Chin University of Texas Southwestern Medical Center
Principal Investigator: Ronald Oudiz Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
  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: August 7, 2020
Last Verified: July 2020

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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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Familial Primary Pulmonary Hypertension
Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases