PROTECT-APT 1: Early Treatment and Post-Exposure Prophylaxis of COVID-19

NCT05954286 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: PC06
• Study Type: interventional
• Target: 92
• Locations: 4 countries
• Sites: 6

Brief Summary

This study is an adaptive, randomized, double blind, platform trial evaluating promising investigational products (IP) for safety and efficacy as early outpatient treatment and post-exposure prophylaxis for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

Conditions

SARS-CoV-2

Keywords

COVID-19; Early Treatment; Post-Exposure Prophylaxis; Outpatient

Outcome Measures

Primary Outcomes (1)

• Time to Sustained Alleviation or Resolution of COVID-19 Symptoms

  Defined as the number of days from randomization within a PSA to the first day the participant reports all symptoms as mild or none for at least 3 consecutive days. Symptoms will be assessed via completion of a Screening Symptom Questionnaire at Enrollment and then a Daily Follow Up Symptom Questionnaire.

  Day 0 to Day 28

Secondary Outcomes (7)

• Change in Overall COVID-19 Symptom Severity Score

  Day 0 to Day 28

• Time to Negative SARS-CoV-2 PCR

  Day 0 to Week 12

• Development of New Severe COVID-19 Symptoms

  Day 0 to Week 12

• Return to Usual State of Health

  Day 0 to Week 12

• Return to Usual Activities

  Day 0 to Week 12

Other Outcomes (1)

• Incidence of AEs Causing IP Discontinuation

  Day 0 to Week 12

Study Arms (2)

Early Treatment: Upamostat 400 mg

EXPERIMENTAL

400 mg (2 x 200 mg) capsules administered orally once daily for 14 days

Drug: Upamostat

Early Treatment: Placebo Oral Capsule

PLACEBO COMPARATOR

The placebo arm may be pooled across more than one experimental arm if multiple investigational drug are available to be tested at the same time and administered in the same way.

Drug: Placebo (PO)

Interventions

Upamostat DRUG

Upamostat is available as a hydrogen sulphate salt (also designated as WX-671.1). WX-671.1 is a white to yellowish powder which is freely soluble in dimethyl sulfoxide and soluble in ethanol. The drug substance is very slightly soluble in water or 0.1 M HCl.

Also known as: WX-671, RHB-107

Early Treatment: Upamostat 400 mg

Placebo (PO) DRUG

Oral Capsules

Early Treatment: Placebo Oral Capsule

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Positive molecular or antigen diagnostic test for SARS-CoV-2 at study enrollment or within ≤ 5 days prior to enrollment
• Presence of two or more Screening Symptoms listed in Supplement 3 with at least two symptoms classified as moderate to severe (and/or ≥ 2 on the frequency questions or loss of taste/smell questions) at the time of enrollment a. For participants who have preexisting conditions causing mild or moderate symptoms listed on the Screening Symptom Questionnaire, there must be an increase of at least one severity level for that symptom at enrollment (For example, prior to illness participant routinely experienced headaches rated as moderate severity, now rating headache as severe at enrollment)
• Supplement 3 Screening Symptoms: stuffy or runny nose, hoarse voice, sore throat, difficulty breathing, cough, fatigue (low energy or tiredness), muscle or body aches, headache, fever (documented temperature \> 38° C \[100.4° F\]) or subjective fever, chills or shivering, feeling hot or feverish, nausea, vomiting, diarrhea, loss of smell, loss of taste
• Symptom onset ≤ 5 days prior to enrollment

You may not qualify if:

• Hospital admission at the time of enrollment
• Hospitalization will be defined as requiring medical care not available in an outpatient setting for greater than 24 hours
• Laboratory confirmed SARS-CoV-2 infection 6 to 90 days prior to enrollment
• Oxygen saturation \< 92% on room air
• Baseline use of supplemental oxygen at the time of enrollment
• Presence of any of the following comorbidities that per the PI puts the patient at high risk of developing severe COVID-19 illness:
• a. Age ≥ 75 years b. Active treatment for solid tumor and hematologic malignancies c. Hematologic malignancy, myeloma, or related disorder (e.g., myelodysplastic syndrome, myelofibrosis) d. Receipt of solid-organ transplant or an islet transplant and taking immunosuppressive therapy e. Chemotherapy or radiotherapy for solid organ cancer in the last 12 months f. Receipt of chimeric antigen receptor (CAR)-T-cell therapy or hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppressive therapy) g. Moderate or severe primary immunodeficiency (e.g., common variable immunodeficiency disease, severe combined immunodeficiency, DiGeorge syndrome, Wiskott-Aldrich syndrome) h. Advanced or untreated HIV infection (people with HIV and CD4 cell counts less than 200/mm3, history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV) i. Active treatment with high-dose corticosteroids (i.e., 20 or more mg of prednisone or equivalent per day when administered for 2 or more weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, tumor necrosis factor (TNF) blockers, and other biologic agents that are immunosuppressive or immunomodulatory j. Sickle cell disease k. Chronic liver disease (e.g., Child-Pugh Class A, B or C cirrhosis) l. Down syndrome m. Dementia or neurocognitive disability (e.g., Parkinson's disease) n. Participants with 3 or more of the following conditions: i) No prior COVID-19 infection OR has not completed a COVID-19 vaccine series within the last 6 months OR has not received a vaccine booster within the last 6 months ii) Age 65-74 years iii) BMI ≥35 (or \>95th percentile in adolescents) iv) Type 1 or type 2 diabetes mellitus v) Cardiovascular disease (including HTN if age \>55) vi) Chronic lung disease (including bronchiectasis, CF, COPD, ILD, PHTN, PE, moderate-to-severe asthma) vii) Chronic kidney disease (eGFR \<30)
• Participants who are receiving or plan to receive anti-SARS-CoV-2 antivirals for treatment of their COVID-19
• Population B: Uninfected adult contacts of symptomatic SARS-CoV-2 infected individuals
• Age ≥ 18 years
• Asymptomatic contact of an individual with laboratory confirmed SARS-CoV-2 infection defined as:
• a. Indoor exposure to the symptomatic case or cases within 6 feet (2 meters) for ≥ 15 minutes over a 24-hour period without the use of personal protective equipment
• Negative screening SARS-CoV-2 molecular or antigen diagnostic test performed at screening or within less than or equal to 24 hours of enrollment
• Exposure and enrollment within 6 days or less from when the symptomatic, confirmed SARS-CoV-2 positive case first had symptoms
• \. Symptoms attributed to COVID-19 as assessed by the investigator 2. Positive molecular or antigen diagnostic test for SARS-CoV-2 from any upper respiratory specimen within 90 days prior to enrollment 3. SARS-CoV-2 vaccination within 90 days prior to enrollment EXCEPT if severely immunocompromised or a known vaccine non-responder 4. Severely immunocompromised or a known vaccine non-responder defined as: solid organ or stem cell transplant recipient, B cell leukemia, receiving B cell depletion therapy (e.g., rituximab), agammaglobulinemia, or negative serology ≥2 weeks after vaccination with two doses of a vaccine 5. Hospital admission at the time of enrollment

Sponsors & Collaborators

• Henry M. Jackson Foundation for the Advancement of Military Medicine: lead
• Joint Program Executive Office Chemical, Biological, Radiological, and Nuclear Defense Enabling Biotechnologies: collaborator
• RedHill Biopharma Limited: collaborator
• FHI Clinical, Inc.: collaborator

Study Sites (6)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

KUR Research

Nashville, Tennessee, 37209, United States

Location

Josha Research

Bloemfontein, 9300, South Africa

Location

Royal Thai Army Clinical Research Center (RTA CRC) Royal Thai Army-Armed Forces Research Institute of Medical Sciences (RTA-AFRIMS)

Bangkok, 10400, Thailand

Location

Makerere University Walter Reed Project

Fort Portal, Uganda

Location

MeSH Terms

Conditions

COVID-19

Interventions

upamostat

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. Kristen Pettrone
• Organization: Henry Jackson Foundation for the Advancement of Military Medicine

kpettrone@aceso-sepsis.org

(240) 694-2000

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: An adaptive, randomized, double-blind, platform trial

Study Record Dates

• First Submitted: March 30, 2022
• First Posted: July 20, 2023
• Study Start: January 29, 2024
• Primary Completion: April 24, 2025
• Study Completion: April 24, 2025
• Last Updated: April 17, 2026
• Results First Posted: February 13, 2026

Record last verified: 2026-01

Locations

TH (1); UG (1); ZA (1); US (3)