Hormonal intervention for the treatment of veterans with COVID-19 requiring hospitalization (HITCH): a multicenter, phase 2 randomized controlled trial of best supportive care vs best supportive care plus degarelix: study protocol for a randomized controlled trial
Authors: Nickols Nicholas G. , Goetz Matthew B. , Graber Christopher J. , Bhattacharya Debika , Soo Hoo Guy , Might Matthew , Goldstein David B. , Wang Xinchen , Ramoni Rachel , Myrie Kenute , Tran Samantha , Ghayouri Leila , Tsai Sonny , Geelhoed Michelle , Makarov Danil , Becker Daniel J. , Tsay Jun-Chieh , Diamond Melissa , George Asha , Al-Ajam Mohammad , Belligund Pooja , Montgomery R. Bruce , Mostaghel Elahe A. , Sulpizio Carlie , Mi Zhibao , Dematt Ellen , Tadalan Joseph , Norman Leslie E. , Briones Daniel , Clise Christina E. , Taylor Zachary W. , Huminik Jeffrey R. , Biswas Kousick , Rettig Matthew B. 
Published: July 2021

Background

Therapeutic targeting of host-cell factors required for SARS-CoV-2 entry is an alternative strategy to ameliorate COVID-19 severity. SARS-CoV-2 entry into lung epithelium requires the TMPRSS2 cell surface protease. Pre-clinical and correlative data in humans suggest that anti-androgenic therapies can reduce the expression of TMPRSS2 on lung epithelium. Accordingly, we hypothesize that therapeutic targeting of androgen receptor signaling via degarelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, will suppress COVID-19 infection and ameliorate symptom severity.

Methods

This is a randomized phase 2, placebo-controlled, double-blind clinical trial in 198 patients to compare efficacy of degarelix plus best supportive care versus placebo plus best supportive care on improving the clinical outcomes of male Veterans who have been hospitalized due to COVID-19. Enrolled patients must have documented infection with SARS-CoV-2 based on a positive reverse transcriptase polymerase chain reaction result performed on a nasopharyngeal swab and have a severity of illness of level 3–5 (hospitalized but not requiring invasive mechanical ventilation). Patients stratified by age, history of hypertension, and severity are centrally randomized 2:1 (degarelix: placebo). The composite primary endpoint is mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at 15 after randomization. Important secondary endpoints include time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a normal temperature, and the maximum severity of COVID-19 illness. Exploratory analyses aim to assess the association of cytokines, viral load, and various comorbidities with outcome. In addition, TMPRSS2 expression in target tissue and development of anti-viral antibodies will also be investigated.

Discussion

In this trial, we repurpose the FDA approved LHRH antagonist degarelix, commonly used for prostate cancer, to suppress TMPRSS2, a host cell surface protease required for SARS-CoV-2 cell entry. The objective is to determine if temporary androgen suppression with a single dose of degarelix improves the clinical outcomes of patients hospitalized due to COVID-19.

Trial registration

ClinicalTrials.gov NCT04397718. Registered on May 21, 2020