*Phase Ib study to evaluate the safety, PK and antiviral activity of RV299 against RSV.
Research type
Research Study
Full title
A randomised, phase 1b, double-blind, placebo-controlled study to evaluate the safety, pharmacokinetics and antiviral activity of RV299 against Respiratory Syncytial Virus in the viral challenge model.
IRAS ID
1005624
Contact name
Heather Welch
Contact email
Sponsor organisation
ReViral Limited
ISRCTN Number
ISRCTN11937043
Research summary
The purpose of this study is to investigate if an experimental drug called RV299 may be useful in treating people infected with Respiratory Syncytial Virus (RSV). RSV spreads from person to person by close contact with infected individuals, through droplets, or through contaminated surfaces . The only approved treatment for RSV infection is a drug called Ribavirin but because of its unwanted side effects, and low effectiveness, it is rarely used. There are vaccines in development for the prevention of RSV, however these are not currently approved for use. Therefore, we need an effective treatment for RSV infection. Up to 80 volunteers, 18-55 years of age, who consent to the participation in this research will be invited to a Quarantine unit at hVIVO, to stay for approximately 15 days. Participants will be randomly allocated to one of two treatment groups to receive either RV299 or Placebo. Eligible participants will be administered (inoculated with) the study virus on Study Day 0. To test the study drug, on Study Day 2, we will start to collect and test twice daily nasal wash samples to see if participants have become infected with the study virus. When the nasal wash sample shows that they have become infected, they will receive the first dose of the study drug (or placebo). On Study Day 5, if the nasal wash sample does not yet show infection, all remaining participants will receive the first dose of study drug (or placebo). All participants will receive the study drug or placebo twice daily for 5 consecutive days, a total of 10 doses. After completion of the Quarantine phase, participants will need to return for a final follow up visit approximately 28 days (±3 days) from the date they receive the study virus.
Lay summary of study results:
This was a single-center, randomized, double-blind, placebo-controlled, proof-of-concept study in healthy adult male and female participants from 18 to 55 years of age, inclusive. The primary objective was to assess the antiviral activity of RV299 against RSV in the viral challenge model. In addition, safety, tolerability, and PK of RV299 were assessed. A total of 80 participants was planned to be enrolled in this study: 40 participants on RV299 and 40 participants on placebo. The study consisted of a screening phase, a quarantine inpatient phase and a follow up phase. In total, 82 participants were enrolled and received challenge virus. Subsequently, 79 participants were randomized to RV299 (n=39) or placebo (n=40). No notable differences were observed between the treatment groups in age, sex, race, and BMI at screening. The majority (45 [57.0%]) of participants were male. The mean age was 25.9±6.7 years and ranged between 18 and 53 years. Most participants (60 [75.9%]) were White. The mean BMI was 25.1±3.7 kg/m2 and ranged between 18.4 and 34.2 kg/m2. RV299 (65 mg) or placebo was dosed twice daily (~12 hours interval) for 5 consecutive days (a total of 10 doses). All participants in the RV299 group received all the planned doses of RV299. All but 1 participant in the placebo group received the planned doses. One participant withdrew from the study due to family bereavement and did not receive doses 9 and 10. Therefore, compliance ([number of doses received/number of doses expected] × 100) was between 80 to 100% for all participants. For the primary efficacy endpoint, viral load was significantly reduced (by 48.99%; following RV299 treatment compared with placebo, confirming that the primary objective of the study was achieved. Repeated administration of RV299 was safe and well tolerated, as was challenge virus inoculation with RSV-A Memphis 37b. No SAEs were reported, no treatment-emergent adverse events (TEAE) led to withdrawal from the study, and no TEAEs led to discontinuation from IMP. In total 12 AEs were assessed to be at least possibly related to challenge virus inoculation (n=7 for RV299 and n=5 for placebo. RV299 was rapidly absorbed in the blood after single and multiple (twice daily) oral doses of 65 mg. Overall, the results demonstrate that RV299 at a dose of 65 mg (dosed twice daily for 5 consecutive days [a total of 10 doses]) is safe and well tolerated, and effective in reducing viral load of RSV infection in the viral challenge model.REC name
London - Riverside Research Ethics Committee
REC reference
22/FT/0077
Date of REC Opinion
22 Jun 2022
REC opinion
Further Information Favourable Opinion