A Study to Evaluate the Efficacy and Safety of Proxalutamide (GT0918) in Hospitalized COVID-19 Subjects

Covid19 Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-Controlled, Phase III Study to Evaluate the Efficacy and Safety of Proxalutamide (GT0918) in Hospitalized COVID-19 Subjects

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05009732
• Other study ID #: GT0918-US-3002
• Status: Terminated
• Phase: Phase 3
• Start date: September 30, 2021
• Est. completion date: July 14, 2023

Study information

• Verified date: August 2023
• Source: Suzhou Kintor Pharmaceutical Inc,
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is an adaptive Phase III randomized double-blind placebo-controlled trial to evaluate the efficacy and safety of Proxalutamide (GT0918) in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted globally. The study will compare GT0918 plus standard of care (SOC) with the placebo plus SOC. Approximately 762 subjects will be randomized in a 1:1 ratio to either GT0918 plus SOC or placebo plus SOC group.

Description:

Coronavirus disease 2019 (COVID-19) emerged in late 2019 and spread rapidly, resulting in a global pandemic.SARS-CoV-2 encodes nonstructural and structural proteins required for its viral life cycle. Among them, the spike glycoprotein plays a pivotal role in SARS-CoV-2 infection by recognizing and attaching to ACE2 transmembrane protein on host cells. Kintor protocol has been designed to evaluate efficacy and safety of GT0918 in hospitalized subjects with COVID-19 illness. The target population of this study are hospitalized subjects with COVID-19 illness with positive SARS-CoV-2 virus test within 72 hours of randomization. The study will evaluate anti-androgen therapy may effectively prevent progression to the more severe form of COVID-19 illness and death, shorten the time to sustained recovery and decrease the mortality rate. Subject will receive either GT0918 plus standard of care or matched placebo plus standard of care. GT0918/placebo will be given 300mg orally once a day around 30 minutes after meal for 7 days and can be extended up to 14 days per investigator discretion

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 139
• Est. completion date: July 14, 2023
• Est. primary completion date: February 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures.

2. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.

3. Male and non-pregnant female subjects with age =18 years of age at the time of randomization.

4. Admitted to a hospital with symptoms suggestive of severe COVID-19.

5. Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other commercial or public health assay (including rapid antigen test) in any specimen, as documented by either of the following:

• PCR positive in sample collected < 72 hours prior to randomization; OR

• PCR positive in sample collected = 72 hours prior to randomization, documented inability to obtain a repeat sample (e.g. due to lack of testing supplies, limited testing capacity, results taking > 24 hours, etc) AND progressive disease suggestive of ongoing SARS-CoV-2 infection.

6. Illness of any duration, and at least one of the following:

• Shortness of breath, RR=30 /minute

• Clinical signs indicative of progressive aggravation, lung radiographic infiltrates by imaging (chest x-ray, CT scan, etc.) showing >50% progression within 24-48 hours

• PaO2/FiO=300mmHg 1mmHg=0.133kPa

• Resting state SpO2 = 93% on room air

7. All women of childbearing potential defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal. Highly effective contraception methods include:

• Total Abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception, or

• Use of one of the following combinations (a+b or a+c or b+c):

1. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception.

2. Placement of an intrauterine device (IUD) or intrauterine system (IUS);

3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository;

• Female sterilization (have had prior surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment;

• Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject;

• In case of use of oral contraception women should have been stable for a minimum of 3 months before taking study treatment. Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment, is she considered not of childbearing potential;

8. Regardless of their fertility status, male subjects must agree to either remain abstinent (if this is their preferred and usual lifestyle) or use condoms as well as one additional highly effective method of contraception (less than 1% failure rate) or effective method of contraception with nonpregnant women of childbearing potential partners for the duration of the study and until 90 days after the last dose. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.

9. Agree not to participate in another clinical trial for the treatment of COVID-19 through Day 60 after first dose.

Exclusion Criteria:

Subjects are excluded from the study if any of the following criteria apply:

1. ALT/AST > 3 times the upper limit of normal.

2. Serum total bilirubin > 1.5 x ULN (upper limit of normal)

3. Estimated glomerular filtration rate (eGFR) < 30 ml/min (including patients receiving hemodialysis or hemofiltration).

4. Subjects with significant cardiovascular disease as following:

i. heart failure NYHA class =3 ii. left ventricular ejection fraction <50% iii. those with a history of cardiac arrhythmias, including long QT syndrome.

5. Neutropenia (absolute neutrophil count <1000 cells/µL) (<1.0 x 10^3/µL).

6. Lymphopenia (absolute lymphocyte count <200 cells/µL) (<0.20 x 10^3/µL)

7. Pregnancy or breast feeding

8. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours.

9. Allergy to any study medication.

10. Received monoclonal antibody, convalescent plasma, or intravenous immunoglobulin [IVIg]) for COVID-19 withing 14 days of screening.

11. Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking investigational product.

12. Have a history of VTE (deep vein thrombosis [DVT] or pulmonary embolism [PE]) within 12 weeks prior to screening or have a history of recurrent (>1) VTE (DVT/PE).

13. Subject taking or had taken an anti-androgen of any type including androgen depravation therapy, 5-alpha reductase inhibitors, etc. within 3 months before dosing.

14. Have participated, within the last 30 days before dosing, in a clinical study involving an investigational intervention. If the previous investigational intervention has a long half-life, 5 half-lives or 30 days, whichever is longer, should have passed.

15. Subjects with active myopathy

16. Is admitted to Intensive Care Units at randomization

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Drug:
• GT0918
300mg once daily orally
• Standard of care
Local standard of care per written policies or guidelines
• Matching placebo
Matching placebo

Locations

Country	Name	City	State
China	Beijing Ditan Hospital Capital Medical University	Beijing
China	Shanghai Public Health Clinical Center	Jinshan	Shanghai
China	The Third People's Hospital of Shenzhen	Longgang	Shenzhen
Philippines	Davao Doctors Hospital	Davao City	Davao
Philippines	St. Paul's Hospital	Iloilo City	Iloilo
Philippines	Philippine General Hospital	Malina	Metro Malina
Philippines	Mary Johnston Hospital (MJH)	Manila	Metro Manila
Philippines	Lung Center of the Philippines	Quezon City
Philippines	Quirino Memorial Medical Center	Quezon City	Metro Manila
South Africa	Johese Clinical Research: Unitas	Centurion
South Africa	Drs Sarvan and Moodley	Durban
South Africa	TASK Eden	George
South Africa	Johese Clinical Research ZAH	Pretoria
South Africa	Dr JM Engelbrecht Practice, Vergelegen Mediclinic	Somerset
South Africa	Clinical Projects Research	Worcester
Ukraine	Communal Noncommercial Profit	Dnipro	Dnipro Oblast
Ukraine	Ivano-Frankivsk Clinical Regional Infectious Diseases Hospital	Ivano-Frankivsk	Ivano-Frankivsk Oblast
Ukraine	CNE of Kharkov RC Reg Cl Infectious Hospital	Kharkiv	Kharkiv Oblast
Ukraine	Kharkiv city clinical hospital #13	Kharkiv	Kharkiv Oblast
Ukraine	City Clinical infectious Hospital	Odesa	Odesa Oblast
Ukraine	Poltava Regional Clinical	Poltava	Poltava Oblast
Ukraine	CCH #1 Vinnytsia M.I.Pyrogov NMU Ch of Infectious Diseases	Vinnytsia	Vinnytsia Oblast
United States	Raymond G. Murphy VA Medical Center	Albuquerque	New Mexico
United States	Medical City Fort Worth	Fort Worth	Texas
United States	Hannibal Clinic (HC)	Hannibal	Missouri
United States	Alternative Research Associates LLC.	Hialeah	Florida
United States	Sparrow Hospital	Lansing	Michigan
United States	PRX Research	Mesquite	Texas
United States	Saint Lawrence Health System	New York	New York
United States	Ascension St. John Medical Center	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Suzhou Kintor Pharmaceutical Inc,

Countries where clinical trial is conducted

United States,  China,  Philippines,  South Africa,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The time to Clinical deterioration is evaluated by Day 30.	Clinical deterioration is defined as the need for intensive care unit level care (ICU) or invasive mechanical ventilation/ECMO or all-cause mortality by Day 30.	30 days from enrollment
Secondary	60-day mortality	All cause mortality at 60 days after enrollment	60 days from enrollment