A Study to Learn About the Safety, Tolerability and Blood Levels of a Study Medicine (called sisunatovir) in Infants and Children with RSV Lower Respiratory Tract Infection.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2023-11-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pfizer Inc

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Safety, Dose response

To evaluate the safety and tolerability of sisunatovir compared to placebo in participants with RSV-LRTI

Secondary objectives 1

1. To characterize the PK of sisunatovir in participants with RSV-LRTI.

Conditions and MedDRA coding

Respiratory Syncytial Virus (RSV) Infection

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Participants 1 day to ≤60 months of age and weight ≥2.5 kg to ≤23 kg
2. A positive RSV diagnostic test with result available in source document to confirm eligibility either according to routine site practice or Investigator sites may use RSV POC test kits that are provided for this study. RSV diagnostic test, antigen or molecular test is acceptable, and should be collected within 48 hours of randomization. Note: Participants ≤30 days old with RSV diagnostic test collected within 72 hours is acceptable for eligibility.
3. Evidence of LRTI by the presence of ≥1 from any of the following 4 categories (a through d): a.Increased respiratory rate for age: •<2 months: ≥60 bpm •≥2 to <12 months: ≥50 bpm •≥12 to ≤60 months: ≥40 bpm b.SpO2 < 95% on room air c.Increased respiratory effort as evidenced by ≥1 of the following: •Grunting with expiration •Nasal flaring •Retractions d.One or more of the following exam findings on auscultation: •Wheezing •Rhonchi •Rales or crackles
4. For participants >30 days old, RSV-related signs and/or symptoms must be present for ≤5 days at time of randomization. For participants 1 day to 30 days old, RSV related signs and/or symptoms must be present within ≤7 days at time of randomization.

Exclusion criteria 17

1. 1. Any medical, developmental, or behavioral condition (including history of self-harmful behaviors) or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
2. 10. Suspected or confirmed clinically significant moderate or severe bacterial infection (eg, bacterial pneumonia, bacteremia), that may interfere with the evaluation of response to the study intervention at investigator discretion. Participants with mild, localized infections such as otitis media or UTI can be included.
3. 11. Evidence of severe respiratory failure requiring invasive mechanical ventilation or ECMO. Note: Participants requiring non-invasive ventilation, including high flow nasal cannula (HFNC), remain eligible for the study
4. 12. Known to have significant comorbidities, including genetic disorders (eg, trisomy 21); cardiopulmonary diseases (eg, hemodynamically significant congenital heart disease); significant pulmonary disease (eg, bronchopulmonary dysplasia, cystic fibrosis); history of renal failure including renal anomalies likely to be associated with renal insufficiency (eg, renal dysplasia, polycystic renal disease, renal agenesis); history of surgery for diaphragmatic hernia; any hereditary or acquired metabolic diseases, hematological or other malignancy; or is known to be HIV positive; or has evidence of severe neurologic impairment or developmental delay that would limit the ability to administer IMP or evaluate the safety or clinical response to IMP.
5. 13. Immunosuppressive disease (eg, bone marrow or organ transplantation or primary immune deficiencies) OR prolonged use of immune-weakening medications. • Has received corticosteroids equivalent to prednisone ≥2mg/kg daily for at least 14 consecutive days within 30 days prior to study start. Inhaled/nebulized or topical (skin, eyes or ears) corticosteroids are permitted, except those prohibited (see Section 6.9). • Has received treatment with biologics (eg, infliximab, ustekinumab), immunomodulators (eg, methotrexate, 6MP, azathioprine) or cancer chemotherapy within 90 days prior to study start.
6. 14. Malformation of the gastrointestinal tract including unresolved pyloric stenosis, history of necrotizing enterocolitis, short bowel, or other significant condition that would alter drug absorption or increase the risk of diarrhea.
7. 15. Has significant oral and/or maxillofacial malformations that would limit the ability to administer IMP.
8. 16. Allergy to test medication or constituents.
9. 17. Current use of any prohibited concomitant medication(s) or participants unwilling or unable to use a required concomitant medication(s). Refer to Section 6.9 • Has taken within 5 half-lives plus 14 days before dosing, or requires during the dosing period of the study, any drug that could impact the PK of the investigational product, including any prescription medications, OTC medications, herbal remedies or dietary supplements containing St. John’s Wort or the consumption of grapefruit, Seville orange, or cranberry juice-containing products as these are known to be potent inhibitors or moderate or potent inducers of CYP3A4.
10. 2. Premature infants (gestational age less than 35 weeks) AND <1 year of post-natal age. Note: Infants 35- and 36-week gestational age are permitted if they weigh at least 2.5 kg and are at least 2 months post-natal age.
11. 3. Neonates (1 to 30 days old) with intrauterine growth restriction defined by having 3 or more of the following: • Birth weight <10th percentile on population-based or customized growth charts • Head circumference <10th percentile • Length <10th percentile • Prenatal diagnosis of fetal growth restriction • Maternal pregnancy information associated with fetal growth restriction (eg, hypertension, pre-eclampsia)
12. 4. Any clinically significant ECG abnormality in a participant's medical history, or in the pre-dose ECG that per investigator judgement may affect participant safety or interpretation of study results. Note: If sinus tachycardia is present, and not worse than expected due to underlying disease, participant may be considered if it does not interfere with evaluation of response to study intervention, at investigator discretion.
13. 5. Participant history or risk factors for QT prolongation or torsades de pointes (eg, organic heart disease, hypokalemia, hypomagnesaemia, congenital long QT syndrome) or congenital deafness. Family history of long QT syndrome or sudden unexplained death.
14. 6. Known history of hepatic disease, concern for active acute or chronic viral hepatitis, or acute hepatic failure.
15. 7. Participants >30 days only: Known history of AST, ALT or T bili abnormalities >2 x ULN within 6 months of screening. Laboratory assessments not required at screening for participants >30 days unless deemed necessary by the investigator to confirm normal hepatic function.
16. 8. History of epilepsy or seizures. Participants with a history of febrile seizures will be permitted to enroll.
17. 9. Expected to receive an antiviral for another viral infection (eg, influenza or COVID-19) within 10 days of screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Incidence of TEAEs
2. Incidence of AEs and SAEs leading to discontinuations
3. Incidence of clinically significant abnormal laboratory values, ECG parameters and vital signs

Secondary endpoints 1

1. Plasma concentrations of sisunatovir at steady state (Day 3 or later)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Trials.gov Call Centre

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Trials.gov Call Centre

Third parties 7

Locations

2 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications