A Phase 2a Open-Label Study in Infants with REspiratory Syncytial VIRus Lower RespirAtory Tract Infection, Followed by a DoubLe-blind, Placebo-controlled Part, to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Effect of RV521 (REVIRAL 1)

PHRR190424-002103

REVC003

2018-CT0471

A Phase 2a Open-Label Study in Infants with REspiratory Syncytial VIRus Lower RespirAtory Tract Infection, Followed by a DoubLe-blind, Placebo-controlled Part, to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Effect of RV521 (REVIRAL 1)

REVC003 is a phase 2a open-label study in infants with RSV lower respiratory tract infection (LRTI), followed by a double-blind, placebo-controlled part, to evaluate the safety, tolerability, pharmacokinetics (PK) and antiviral effect of RV521.

Terminated

Protocol Amendment pending approval

Infants with RSV

To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with Respiratory Syncytial Virus (RSV) lower respiratory tract infection (LRTI)

To characterise the pharmacokinetics (PK) of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with RSV LRTI

Pending

• Philippines

Clinical Trial

20181019131902

2019-03-26

0000-00-00

20

Unspecified

Unspecified

2020-02-28

Inclusion criteria:

To be eligible for study entry, subjects must satisfy all of the following criteria at the Screening Visit:

1. Male or female ≥ 1 month and ≤ 24 months of age
2. Weigh ≥ 3.5 kg
3. Hospitalised because of RSV LRTI (bronchiolitis or bronchopneumonia). For Part B of the study, it is expected that symptoms will start within 1week before the Screening Visit
4. A positive RSV diagnostic test (RSV infection confirmed either according to routine site practice [polymerase chain reaction ordiagnostic quick test], or using a [Sponsor-provided] commercial kit.)
5. Expected to remain in the hospital for the duration of the study: 3 days for Part A and 7 days for Part B (according to the Investigator’s judgement)
6. Normal psychomotor development (according to the Investigator’s judgement)
7. The parent(s)/legal guardian(s) of the subject must have provided written informed consent for the subject to participate
8. The parent(s)/legal guardian(s) are able and willing to comply with the study protocol

Exclusion Criteria:

Subjects will be excluded from the study if 1 or more of the following criteria are applicable at the Screening Visit:

1. Premature (gestational age less than 37 weeks)
2. Known to have significant comorbidities, including genetic disorders (eg, trisomy 21); cardiopulmonary diseases (eg, haemodynamically significant congenital heart disease); pulmonary disease (eg, REVC003 Page 10 of 83 v. 1.0_30 Jul 2018 bronchopulmonary dysplasia, cystic fibrosis); history of surgery for diaphragmatic hernia; any hereditary or acquired metabolic diseases; hematological or other malignancy; or is known to be HIV positive
3. Known to be immunocompromised
4. Presence of active severe atopic dermatitis requiring daily use of topical anti-inflammatory (corticosteroid or equivalent)
5. History of asthma (per Global Initiative for Asthma [GINA] guidelines), bronchial hyperreactivity, and or allergy/atopy
6. Suspected of having a clinically relevant bacterial infection
7. Has been ventilated or received supplemental oxygen in the 4 weeks before the Screening Visit (except for oxygen via nasal cannula, simple face mask, or headbox, applied for the current RSV infection). Subjects will be permitted to receive supplemental oxygen during the study.
8. Has significant oral and/or maxillofacial malformations
9. History of renal failure including renal anomalies likely to be associated with renal insufficiency (eg, clinical conditions of renal dysplasia, polycystic renal disease, renal agenesis)
10. Clinical evidence of hepatic decompensation (eg, hepatic disorder with associated coagulopathy or associated encephalopathy) or,significantly elevated liver enzymes, (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT] > 3 × the upper limit of normal)
11. History of epilepsy or seizures, including febrile seizures

Interventional

RV521

RV521, a potent small molecule inhibitor of RSV fusion protein mediated cell-cell fusion, and of RSV infection, is formulated as a solution for oral administration. The RV521 Liquid Dosage Form tutti frutti (TF) consists of RV521 Drug Substance in a solution, at a concentration of 5 mg/mL, containing Hydroxypropyl-ẞ-cyclodextrin (HBP cyclodextrin), Lycasin, flavouring agent (Tutti-frutti [TF]), acesulfame potassium, potassium sorbate, acetic acid, and water. Placebo Liquid Dosage Form TF contains the identical ingredients to the RV521 Liquid Dose Form TF with the exception of the active ingredient, RV521.

None

Non-Randomized

Open Label

Unspecified

Single

To evaluate the safety and tolerability of single (Part A) and multiple (Part B) oral doses of RV521 in infants hospitalised with Respiratory Syncytial Virus (RSV) lower respiratory tract infection (LRTI)

Phase II