Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Prostatic Neoplasms

Syndrome

COVID-19

Prostatic Hyperplasia

Hyperplasia

Severe Acute Respiratory Syndrome

Alopecia

Alopecia Areata

Pneumonia

Pneumonia, Viral

Communicable Diseases

Respiratory Tract Infections

Virus Diseases

Coronavirus Infections

Coronaviridae Infections

Nidovirales Infections

RNA Virus Infections

Lung Diseases

Respiratory Tract Diseases

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Hypotrichosis

Hair Diseases

Skin Diseases

Pathological Conditions, Anatomical

Acute Graft Versus Host Disease

All Drugs and Chemicals

Androgens

Androgen Antagonists

Proxalutamide + Usual care as determined by the PI

Proxalutamide

Standard of Care

Flavio A Cadegiani, MD

Andy Goren, MD

This study is intended to explore the possible protective role of anti-androgens in SARS-CoV-2 infection

During the continuing SARS-CoV-2 (COVID-19) pandemic, several studies have reported a significant difference in the rate of severe cases between adult females and adult males (42% vs 58%).Among children under the age of 14, the rate of severe cases was reported to be extremely low. To explain this difference, several theories have been proposed including cigarette smoking and lifestyle habits. However, no theory fits both the gender difference in severe cases as well as reduced risk in pre-pubescent children. Our past research on male androgenetic alopecia (AGA) has led us to investigate an association between androgens and COVID-19 pathogenesis. In normal subjects, androgen expression demonstrates significant variation between men and women as well as between adults and pre-pubescent children.

SARS-CoV-2 primarily infects type II pneumocytes in the human lung. SARS-CoV-2 enters pneumocytes, by anchoring to the ACE2 cell surface receptor. Prior to receptor binding, viral spike proteins undergo proteolytic priming by the transmembrane protease, serine 2 (TMPRSS2). TMPRSS2 inhibition or knock down reduces ability of SARS-CoV-1 (a related virus to SARS-CoV-2) to infect cells in vitro. Additionally, TMPRSS2 also facilitates entry of influenza A and influenza B into primary human airway cells and type II pneumocytes.

The human TMPRSS2 gene has a 15 bp androgen response element and in humans, androgens are the only known transcription promoters for the TMPRSS2 gene. In a study of androgen-stimulated prostate cancer cells (LNCaP), TMPRSS2 mRNA expression increase was mediated by the androgen receptor. Further, the ACE2 receptor, also critical for SARS-CoV-2 viral infectivity, is affected by male sex hormones with higher activity found in males.

Androgenetic alopecia (AGA), often referred to as male pattern hair loss, is the most common form of hair loss among men. The development of androgenetic alopecia is androgen mediated and is dependent on genetic variants found in the androgen receptor gene located on the X chromosome; thus, it is hypothesized that men with AGA would be more prone to severe COVID-19 disease. The investigators conducted a preliminary observational study of hospitalized COVID-19 patients at two Spanish tertiary hospitals between March 23-April 6, 2020 to test this theory. In total, 41 Caucasian males admitted to the hospitals with a diagnosis of bilateral SARS-CoV-2 pneumonia were analyzed. The mean age of patients was 58 years (range 23-79). Among them, 29 (71%) were diagnosed with AGA (16 (39%) were classified as severe AGA (Hamilton IV or above)) and 12 (29%) did not present clinical signs of AGA. The diagnosis of AGA was performed clinically by a dermatologist. The precise prevalence of AGA among otherwise healthy Spanish Caucasian males is unknown; however, based on published literature, the expected prevalence of a similar age-matched Caucasian population is approximately 31-53%.

Based on the scientific rationale combined with this preliminary observation, the investigators propose to test an anti-androgen as a treatment for patients recently diagnosed with COVID-19.

We have chosen the use of the novel second generation androgen receptor (AR) antagonist proxalutamide as a means for rapid reduction in AR activity. Proxalutamide (GT0918) demonstrates a dual mechanism of action. It is highly effective in inhibiting AR as well as exhibiting pharmacological effects of inducing the down-regulation of AR expression; the mechanism that is not present in bicalutamide and enzalutamide. Additionally, it has been reported that Proxalutamide lowers the expression of ACE2. Both would be beneficial for preventing SARS-CoV-2 entry into lung cells.

This study is intended to explore the possible protective role of anti-androgens in SARS-CoV-2 infection. Provided anti-androgens are effective in reducing the rate of COVID-19 hospitalization, subjects enrolled in this study may experience a lower rate of hospitalization.

This study is designed as a prospective, interventional, placebo controlled, double-blinded, randomized parallel assignment study.

Anti-Androgen Treatment for COVID-19

Percentage of subjects hospitalized due to COVID-19

Applied Biology, Inc.

Usual care as determined by the PI

Usual Care: Care as determined by the PI

Usual Care

Proxalutamide + usual care as determined by the PI

Proxalutamide: 200 mg q.d.

Proxalutamide + Usual Care

Total

Age, Continuous

Sex: Female, Male

Mixed ethnicity (Brazil)

Race/Ethnicity, Customized

Brazil

Region of Enrollment

At least one coexisting conditions: Type 2 diabetes, Hypertension, COPD and Obesity

Coexisting conditions

Director of Clinical Trials

All randomized patients were included. 6 patients from the placebo arm lost to follow-up were assumed to be non-hospitalized (COVID-19 8-point ordinal scale 1) and were included in the intention-to-treat analysis.

COVID-19 Hospitalization

Usual care as determined by the PI

Usualf Care: Care as determined by the PI

Overall Study

Genital Neoplasms, Male

Urogenital Neoplasms

placebo+ADT（Androgen Deprivation Therapy） ，Route of placebo administration: tablet, dosage：300mg , dosage form oral , frequency of administration：QD

placebo

Proxalutamide +ADT（Androgen Deprivation Therapy） ，Route of Proxalutamide administration: tablet, dosage：300mg , dosage form oral , frequency of administration：QD

Hongqian Guo, Phd

Shun Zhang, Phd

Shun zhang, Doctor

Junlong Zhuang, Doctor

This trial aims to evaluate the efficacy and safety of neoadjuvant therapy with Proxalutamide combined with androgen deprivation therapy（ADT）for High risk prostate cancer ，This trial is A randomized, controlled, double-blind, single center.Treatment cycle is 6 months,

Proxalutamide: androgen deprivation therapy（ADT）=2:1

Neoadjuvant Therapy With Proxalutamide Combined With Androgen Deprivation Therapy（ADT）for High Risk Prostate Cancer

A Randomized, Controlled, Double-blind, Single Center，Clinical Trial to Evaluate the Efficacy and Safety of Neoadjuvant Therapy With Proxalutamide Combined With Androgen Deprivation Therapy（ADT）for High Risk Prostate Cancer

The proportion of subjects with no morphologically recognizable cancer cell in tumor specimens after radical prostatectomy

The proportion of subjects that have residual tumors with maximum diameter of 3 mm or less after radical prostatectomy

Hongqian Guo

chief physician

Breast Neoplasms

Breast Diseases

Stage one - Dose climbing:

Each dose cohort will assess toxicity within the 35 days following the first dose of GT0918.

Stage two- the expansion cohort :

30 patients will be enrolled to the 200mg cohort . 15 patients will be enrolled to the 300mg cohort.

Stage1:Dose esclation. Stage2:the expansion cohort where one or no DLT takes place in planned study cohort.

Ke Chen

This study is a multi-center, open-label, dose-esclation I/Ib clinical study to explore safety, efficacy an pharmacokinetics of proxalutamide in patients with metastatic breast cancer.

This study includes two stages, stage I: single- and multiple-dose tolerance and pharmacokinetic study; stage 2: preliminary efficacy and safety study.

This study is a multi-center, open-label, dose-esclation study.

Subjects will be enrolled to the 100mg, 200mg, 300mg, 400mg and 500mg group in turn. Unless DLT was found, the dose esclation will continue. 28 days of DLT observation period is needed after 7-day single dose administration, until disease progression, intolerable toxicities (AEs), or withdrawn consent.

After the completion of stage 1, 2 doses for the stage 2 will be determined. In stage 2, patients with AR-positive metastatic breast cancer will be selected to explore the efficacy and safety of proxalutamide, and biomarkers will be explored.

Safety, Tolerability, and Pharmacokinetics of Proxalutamide Therapy in Women With Metastatic Breast Cancer

Safety, Tolerability, and Pharmacokinetics of Proxalutamide Therapy in Women With Metastatic Breast Cancer: an Open-label, Multi-center, Dose-escalating，Phase I/Ib Study.

Each dose cohort will initially include 3 evaluable patients for assessment of toxicity within the 35 days following the first dose of GT0918.

100 mg, 200 mg, 300 mg, 400 mg or 500 mg of GT0918

Preliminary evaluation of the DCR of GT0918 tablets in AR positive metastatic breast cancer patients, and determination of the recommended dose of proclamine in clinical trials.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Anti-Androgen Treatment for COVID-19	NCT04446429	COVID-19 SARS-CoV2 Androgenetic Al... Prostate Cancer Benign Prostati... SARS (Severe Ac...	Proxalutamide Standard of Car...	18 Years -	Applied Biology, Inc.
Neoadjuvant Therapy With Proxalutamide Combined With Androgen Deprivation Therapy（ADT）for High Risk Prostate Cancer	NCT05076851	Neoadjuvant The...	placebo Proxalutamide	18 Years -	The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Safety, Tolerability, and Pharmacokinetics of Proxalutamide Therapy in Women With Metastatic Breast Cancer	NCT04103853	Metastatic Brea...	Proxalutamide	18 Years -	Suzhou Kintor Pharmaceutical Inc,
Anti-Androgen Treatment for COVID-19	NCT04446429	COVID-19 SARS-CoV2 Androgenetic Al... Prostate Cancer Benign Prostati... SARS (Severe Ac...	Proxalutamide Standard of Car...	18 Years -	Applied Biology, Inc.
Neoadjuvant Therapy With Proxalutamide Combined With Androgen Deprivation Therapy（ADT）for High Risk Prostate Cancer	NCT05076851	Neoadjuvant The...	placebo Proxalutamide	18 Years -	The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Spots Global Cancer Trial Database for proxalutamide