Study of RV521 in the Treatment of Adult Subjects Who Have Undergone HCT With an URTI With RSV

NCT04267822 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: REVC006C5241011
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

RV521 is to being developed to treat RSV infection and disease in susceptible individuals at high risk for complications. This is an international, multicenter, placebo-controlled study. Eligible subjects are adults with a documented symptomatic RSV infection who have undergone HCT transplantation and are moderately to severely immunocompromised. Qualified subjects will be randomized in a 1:1 ratio to receive RV521 or placebo, twice daily for 10 days.

Conditions

RSV Infection; Stem Cell Transplant Complications; Lower Resp Tract Infection

Keywords

RV521; lower respiratory tract complication; HCT; hematopoietic cell transplantation; LRTI; Respiratory tract infection; immunocompromise

Outcome Measures

Primary Outcomes (2)

• Proportion of subjects with a progression to Lower Respiratory Tract Complication (LRTC) during the study

  Progression to LRTC during the study defined as one of the following: * Primary LRTI caused by RSV * Secondary bacterial LRTI * LRTI caused by another pathogen * LRTC of unknown etiology

  Pre-dose baseline (Day 1) through Visit 8 (Day 28)

• Change in RSV nasal viral load (via RT-qPCR)

  RSV change measured by the time-weighted average (DAVG) viral load using RT qPCR

  Pre-dose baseline (Day 1) through study completion; up to Visit 8 (Day 28)

Secondary Outcomes (24)

• Percent of participants who experience AEs, TEAEs, SAEs and withdrawals due to TEAEs

  First dose of study drug through Visit 8 (Day 28)

• Evaluate safety and tolerability of RV521 by assessing changes from baseline in systolic and diastolic BP (vital sign parameters)

  Baseline through Visit 8 (Day 28)

• Evaluate safety and tolerability of RV521 by assessing changes from baseline in body temperature (vital sign parameters)

  Baseline through Visit 8 (Day 28)

• Evaluate safety and tolerability of RV521 by assessing changes from baseline in respiration rate (vital sign parameters)

  Baseline through Visit 8 (Day 28)

• Evaluate safety and tolerability of RV521 by assessing changes from baseline in pulse/heart rate (vital sign parameters)

  Baseline through Visit 8 (Day 28)

Study Arms (2)

RV521 Capsules

EXPERIMENTAL

RV521 is formulated as a dry powder blend of RV521 drug substance with mannitol as excipient. They are a white, opaque capsule and administered orally.

Drug: RV521 oral tablet

RV521 Placebo Capsules

PLACEBO COMPARATOR

RV521 placebo capsules will contain mannitol and microcrystalline cellulose only. They are a white, opaque capsule and administered orally.

Drug: Placebo oral tablet

Interventions

RV521 oral tablet DRUG

Each RV521 dose is four 50 mg dry powder blend capsules, taken orally twice daily for 10 days (20 doses total; 80 capsules total)

Also known as: sisunatovir

RV521 Capsules

Placebo oral tablet DRUG

Each placebo dose is four capsules, taken orally twice daily for 10 days (20 doses total; 80 capsules total)

Also known as: vehicle

RV521 Placebo Capsules

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Diagnosed with Chronic Graft-vs-Host Disease (GVHD), or
• Has used systemic corticosteroids in the 30 days prior to RSV infection
• Has moderate to severe immunocompromise, defined as a score ≥ 5 on the ISI-RSV and/or an ALC of ≤ 500 cells/ mm3
• Documentation of positive RSV infection in the upper airway
• Use of non-marketed investigational agents within 30 days, OR use of an investigational monoclonal anti-RSV antibodies within 4 months or 5 half-lives of screening, whichever is longer, OR use of any investigational RSV vaccines after HCT.
• Receiving a prescription, OTC, or herbal medication that is a potent inducer or inhibitor of CYP3A4, within 2 weeks of Randomization.
• Receiving a prescription, OTC, or herbal medication that is a substrate of CYP3A4 with a narrow therapeutic index where monitoring blood levels is not possible.
• Known chronic infection with hepatitis B, C, or HIV.
• Is in the pre-engraftment period during RSV infection.
• Admitted to the hospital primarily for lower respiratory tract disease of any cause as determined by the Investigator.
• Any condition requiring mechanical ventilation or vasopressor support at the time of randomization.
• Clinically significant bacteremia or fungemia within 5 days prior to Screening that has not been adequately treated.
• Clinically significant bacterial, fungal, or viral pneumonia within 2 weeks prior to Screening that has not been adequately treated.
• Excessive nausea/vomiting at Screening or an inability to swallow capsules.
• Elevation of hepatic enzymes or renal compromise.

Sponsors & Collaborators

• Pfizer: lead

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections; Respiratory Tract Infections

Interventions

sisunatovir

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Diseases

Study Officials

• PfizerCT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The Investigators, Sponsor, Independent Adjudication Committee members, and any personnel involved in the subject's care, assessment, monitoring, data collection, or analysis will be blinded to the subject treatment assignment throughout the conduct of the study. Exceptions to this are limited to a fire-walled-protected, unblinded Data Safety Monitoring Board (DSMB) statistician at the Contract Research Organization (CRO) who will prepare output for the closed session of all DSMB meetings.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A Phase 2, international, multicenter, randomized, double-blind, placebo-controlled study.

Study Record Dates

• First Submitted: February 5, 2020
• First Posted: February 13, 2020
• Study Start: June 15, 2020
• Primary Completion: June 30, 2023
• Study Completion: July 31, 2023
• Last Updated: May 8, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share