Hormonal Intervention for the Treatment in Veterans With COVID-19 Requiring Hospitalization

Study Overview
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Brief Summary
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The purpose of this study is to determine if temporary androgen suppression improves the clinical outcomes of Veterans who are hospitalized to an acute care ward due to COVID-19.

Detailed Description
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A novel coronavirus, now termed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), arose late in 2019. The first confirmed cases occurred in December in Wuhan, Hubei province, China. It now infects people on six continents, spreading person to person. The World Health Organization (WHO) classified it as a global pandemic on March 11, 2020. As of April 6, 2020, there are more than 1.2 million confirmed cases and more than 70,000 deaths attributed to this virus. Every person on Earth, as well as every United States Veteran, is at risk. This is the emergent public health threat of our time. SARS-CoV-2 is a singled stranded RNA virus related to severe acute respiratory syndrome-related coronavirus (SARS-CoV-1). SARS-CoV-2 is thought to be transmissible largely by respiratory droplets or direct contact, but might also be transmitted through aerosolization. SARS-CoV-2 disease severity ranges from no to minimal symptoms, mildly symptomatic with cough and dyspnea, to severe respiratory distress with multi-organ failure requiring admission to an intensive care unit and emergent ventilator support. Although data are evolving, the severity of illness varies with age, co-existing comorbidities, and biological sex, with older age, people with pre-existing cardiovascular disease, and males manifesting greater disease severity. A worldwide effort is in place to contain and suppress human-to-human transmission. These public-health strategies aim to slow the rate of spread and reduce the burden on critical care infrastructure. However, there is also a need effective therapeutics. Vaccine trials are underway but potential approvals are at least a year away. Development of new drugs de novo to treat SARS2-CoV-2 will likely take even longer. Thus, the most expedient therapeutic strategy to confront this pandemic will repurpose existing FDA-approved therapeutics. One potential strategy targets viral components directly, using existing antivirals and anti-infectives currently used for other diseases. Such efforts include trials of hydroxychloroquine, remdesivir, and ribavirin. Another strategy involves targeting the human proteins, rather than viral proteins, required for SARS CoV-2 entry and replication.

Official Title
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Hormonal Intervention for the Treatment in Veterans With COVID-19 Requiring Hospitalization (HITCH): A Multicenter, Phase 2 Randomized Controlled Trial of Best Supportive Care (BSC) vs BSC Plus Degarelix

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Degarelix
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Veterans admitted to a VA hospital. Age > 18 Hospitalized on an acute care ward with a diagnosis of COVID-19 contributing to hospitalization. Positive RT-PCR assay for SARS-CoV-2 on a nasopharyngeal swab sample. Severity of illness of level 3, 4 or 5 on the influenza severity scale (see Appendix A) at the time of randomization. The subject (or legally acceptable representative if applicable) must provide written informed consent for the trial. Exclusion Criteria: History of severe hypersensitivity to degarelix or any component of their respective formulation. History of congenital long QT syndrome or known history of prolonged QT interval corrected by the Fridericia correction formula (QTcF) > 500 msec on electrocardiogram performed at screening. Planned discharge within 24 hours of treatment initiation. Subject is planning to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment. Ongoing usage of a Class IA or Class III antiarrhythmic agent. At least 5 half lives must elapse since any prior use of a Class IA or III antiarrhythmic agent prior to administration of study drug. --Baseline electrolyte abnormalities of Grade 3 or higher (based on CTCAE v5.0 criteria). Patients may be included if baseline electrolyte abnormalities are corrected to Grade 2 or lower prior to study drug administration. Myocardial infarction in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease. Enrollment in another investigational study within 30 days of Day 1. Known psychiatric or substance abuse disorder that would interfere with the requirements of the trial. Child-Pugh Class C liver disease. Use of any of the following hormonal agents within Day 1 of treatment: Androgen receptor antagonists or agonists within 4 weeks, Ketoconazole or abiraterone acetate within 2 weeks, Estrogens or progestins within 2 weeks, Herbal products that contain hormonally active agents within 2 weeks. Unwilling or unable to comply with the study protocol. Any condition, which in the opinion of the investigator, would preclude participation in the trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo + BSC<br>No active, only placebo (2 - prefilled syringes containing 3 ml of 0.9% saline) plus best supportive care. | Other: Saline<br>* 09% Saline<br>|
| Experimental: Degarelix + BSC<br>Active Degarelix (2 - prefilled syringes containing 3 ml of reconstituted Degarelix concentrated to 40mg/ml) plus best supportive care. | Drug: Degarelix<br>* Degarelix is an FDA-approved drug for prostate cancer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of Mortality, Ongoing Need for Hospitalization, or Mechanical Ventilation at Day 15 | Number of Patients who died, had a ongoing need for hospitalization, or was placed on mechanical ventilation at Day 15. | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Clinical Improvement | Time to clinical improvement as defined by a decline of 2 categories or more from the baseline modified 7-category ordinal scale of clinical status of hospitalized influenza patients or hospital discharge, whichever comes first. Participants whose condition worsened, who died, or who withdrew from the study without clinical improvement were censored. The 7-categories were defined as: 1: Not hospitalized with resumption of normal activities; 2: Not hospitalized, but unable to resume normal activities; 3: Hospitalization, not requiring supplemental oxygen; 4: Hospitalization, requiring supplemental oxygen; 5: Hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation; 6: Hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation; 7: Death. | Through discharge (an average of 8 days with a maximum of 2.5 months) | 
| Inpatient Mortality | Number of patients who died during their hospital stay | Through discharge (an average of 8 days with a maximum of 2.5 months) | 
| Duration of Hospitalization | Length of hospital stay (randomization to discharge) | Through discharge (an average of 8 days with a maximum of 2.5 months) | 
| Duration of Intubation | Length of time on mechanical ventilation. Length of mechanical ventilation imputed to maximum length (50 days) for patients who died on mechanical ventilation or who were on mechanical ventilation, but date removed was unknown. Length of mechanical ventilation imputed to 0 for patients never on mechanical ventilation. | Through discharge (an average of 8 days with a maximum of 2.5 months) | 
| Time to Normalization of Temperature. | Length of time for temperature to be less than < 37.5 degree Celsius for 48 hours | Through discharge (an average of 8 days with a maximum of 2.5 months) | 
| Maximum Severity of COVID19 Illness. | Maximum severity score on the modified 7-category ordinal scale of clinical status of hospitalized influenza patients. The 7-categories were defined as: 1: Not hospitalized with resumption of normal activities; 2: Not hospitalized, but unable to resume normal activities; 3: Hospitalization, not requiring supplemental oxygen; 4: Hospitalization, requiring supplemental oxygen; 5: Hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation; 6: Hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation; 7: Death. | Through discharge (an average of 8 days with a maximum of 2.5 months) | 
| Composite of Mortality, Ongoing Need for Hospitalization, or Mechanical Ventilation at Day 30 | Number of Patients who died, had a ongoing need for hospitalization, or was placed on mechanical ventilation at Day 30. | 30 days |