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

Randomized, Double-blind, Placebo-controlled Trial of the Safety, Tolerability, and Efficacy of RV521 in the Treatment of Adult Subjects Who Have Undergone Hematopoietic Cell Transplantation (HCT) With a Documented Upper Respiratory Tract Infection (URTI) With Respiratory Syncytial Virus (RSV)

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.

The purpose of this study is to compare the viral load, safety, tolerability, and clinical efficacy of RV521 compared to placebo. This is a Phase 2, international, multicenter, randomized, double-blind, placebo-controlled study. Up to 200 adult subjects with a documented symptomatic RSV URTI who have undergone HCT within 1 year of randomization and who are moderately to severely immunocompromised will be randomized.

Qualified subjects will be randomized in a 1:1 ratio to receive RV521 capsules or matching placebo twice daily for 10 days. After the completion of the 10-day double-blind treatment period, subjects will be followed for an additional 28 days. Study drug may be taken on an outpatient or inpatient basis, depending on clinical status and site practices. Randomization will be stratified by type of HCT graft and ALC count. There are 9 clinic visits planned for this study.

Inclusion Criteria:

1. Has undergone autologous or allogeneic HCT using any conditioning regimen within 1 year of randomization. Subjects who have undergone HCT more than 1 year before Randomization are eligible if all other inclusion/exclusion criteria are satisfied and under at least one of the following conditions:

   1. Diagnosed with Chronic Graft-vs-Host Disease (GVHD), or
   2. Has used systemic corticosteroids in the 30 days prior to RSV infection

2. Has moderate to severe immunocompromise, defined as a score ≥ 5 on the ISI-RSV and/or an ALC of ≤ 500 cells/ mm3

3. Documentation of positive RSV infection in the upper airway

Exclusion Criteria:

1. 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.
2. Receiving a prescription, OTC, or herbal medication that is a potent inducer or inhibitor of CYP3A4, within 2 weeks of Randomization.
3. 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.
4. Known chronic infection with hepatitis B, C, or HIV.
5. Is in the pre-engraftment period during RSV infection.
6. Admitted to the hospital primarily for lower respiratory tract disease of any cause as determined by the Investigator.
7. Any condition requiring mechanical ventilation or vasopressor support at the time of randomization.
8. Clinically significant bacteremia or fungemia within 5 days prior to Screening that has not been adequately treated.
9. Clinically significant bacterial, fungal, or viral pneumonia within 2 weeks prior to Screening that has not been adequately treated.
10. Excessive nausea/vomiting at Screening or an inability to swallow capsules.
11. Elevation of hepatic enzymes or renal compromise.