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Hydroxychloroquine for COVID-19 PEP

The Hydroxychloroquine for COVID-1919 Post Exposure Prophylaxis has been approved and launched, supported by the COVID-19 Therapeutics Accelerator.  Additional studies are in progress and will be added when they are available.
Efficacy of Hydroxychloroquine for Post-exposure Prophylaxis (PEP) to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Among Adults Exposed to Coronavirus Disease (COVID-19): A Blinded, Randomized Study
Short TitleHydroxychloroquine for COVID-19 PEP
Recruitment statusRecruiting
Official Title: CompoundHydroxychloroquine
Condition/diseaseCOVID-19
Study TypeRandomized control
Estimated EnrollmentUp to 2000
TimeProspective
Study Start DateApril 2020
Estimated Study End DateUp to 3 – 4 months
Actual Study End DateTo be determined
Protocol Registry NumberTo be determined
Regulatory Agency Identifying Number(s)Not applicable
Sponsor NameUniversity of Washington
Funding AgencyBill & Melinda Gates Foundation
Co-Principal InvestigatorsDr. Ruanne V. Barnabas
University of Washington

Dr. Anna Bershteyn
NYU School of Medicine

Synopsis

Rationale

Post-exposure prophylaxis (PEP) is defined as taking antimicrobial medication after being exposed or potentially exposed to an infectious agent to prevent becoming infected.PEP is routinely used for prevention of a variety of viral, bacterial, and parasitic infections, including influenza and human immunodeficiency virus. Based on experience with PEP for other infections, therapy should be started as soon as possible after a recent possible exposure.

Hydroxychloroquine (HCQ) is currently approved for the suppressive treatment and treatment of acute attacks of malaria due to several Plasmodium strains. It is also indicated for the treatment of discoid and systemic lupus erythematosus and rheumatoid arthritis. With the first Food and Drug Administration approval in 1955, safety and tolerability of HCQ are well described.

In vitro, HCQ displays antiviral activity against coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pharmacologic modeling based on observed drug concentrations and in vitro drug testing suggest that prophylaxis at approved doses could prevent SARS-CoV-2 infection and/or ameliorate viral shedding. Clinical trials of HCQ treatment for coronavirus disease (COVID‑19) pneumonia are underway in China under separate protocol(s).

Objectives and Endpoints

COVID-19: coronavirus disease; HCQ: hydroxychloroquine; PEP: post-exposure prophylaxis; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.

ObjectivesEndpoints
Primary
To test the efficacy of HCQ (400 mg orally daily for 3 days then 200 mg orally daily for an additional 11 days, to complete 14 days) prevent incident SARS-CoV-2 infection, compared to ascorbic acid among contacts of persons with SARS-CoV-2 infectionPolymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection (self-collected samples collected daily Day 1 through Day 14 and again 2 weeks later ie., Day 28)
Secondary
To determine the safety and tolerability of HCQ as SARS-CoV-2 PEP in adultsAdverse events
To test the efficacy of HCQ to shorten the duration of SARS-CoV-2 shedding among those with SARS-CoV-2 infection in the HCQ PEP groupSARS-CoV-2 viral shedding by PCR
To test the efficacy of HCQ to prevent incident COVID-19PCR-confirmed COVID-19 diagnosis post start of HCQ therapy
Exploratory
To conduct SARS-CoV-2 viral genotyping to assess the impact of HCQ on viral resistance to HCQ PEPViral genotyping of SARS-CoV-2 in a subset of treated study participants who develop infection
To assess adherence to HCQ PEPSelf-reported daily dosing and study therapy concentration (if in sub-study) in study participants
To evaluate the pharmacokinetics (PK) of HCQ by infection statusHCQ blood concentration
To assess if there is an association between PK of HCQ and the efficacy and safety endpoints evaluatedHCQ blood concentration, tolerability and efficacy

Overall Study Design

This is a randomized, multi-center, placebo-equivalent (ascorbic acid) controlled, blinded study of HCQ PEP for the prevention of SARS-CoV-2 infection in adults exposed to the virus.This study will enroll up to 2000 asymptomatic men and women 18 to 80 years of age (inclusive) at baseline who are close contacts of persons with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 or clinically suspected COVID-19 and a pending SARS-CoV-2 PCR test. Eligible participants will be enrolled and randomized 1:1 to HCQ or ascorbic acid at the level of the household (all eligible participants in 1 household will receive the same intervention).

Participants will be counseled about the preliminary in vitro data on HCQ activity against SARS‑CoV-2 and equipoise regarding efficacy in humans.

Participants may participate in a sub-study where they will be asked to provide a dried blood spot sample for therapy concentration and pharmacokinetics (PK) of HCQ as well as for SARS‑CoV-2 antibody testing, if possible.

An independent data and safety monitoring board (DSMB) will be convened for this study with expertise in COVID-19 or respiratory viruses, PEP, and emerging epidemics; DSMB will include a biostatistician. The purpose of the DSMB is to monitor the study for operational futility, social harms, and efficacy.

If additional data emerge on alternative effective agents for SARS-CoV-2 prophylaxis and/or data about HCQ as PEP, the protocol could be modified through an amendment to evaluate an alternative therapy as PEP.

Number of Participants

Up to 2000 eligible participants will be randomly assigned (at the level of household) 1:1 to study treatment (HCQ or ascorbic acid).

Treatment Groups and Duration

The duration of study participation will be approximately 28 days. Households will be randomized 1:1 (at the level of household), with participants receiving one of the following therapies:

    • HCQ 400 mg orally daily for 3 days then 200 mg orally daily for an additional 11 days
    • Ascorbic acid 500 mg orally daily for 3 days then 250 mg orally daily for 11 days

After 14 days of treatment are completed, participants will be asked to participate in the study for an additional 14 (±3) days.