A Study of Susceptibility to Baloxavir Marboxil in Patients with Influenza and its transmission to their household contacts

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Health Care [N] - Environment and Public Health [N06]

Trial duration

24 Nov 2023 → ongoing

Decision date (initial)

2023-10-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Part A (Surveillance)
To evaluate the prevalence of pre-dose and treatment-emergent polymerase acidic protein (PA) I38X and T20K substitutions and other resistance-associated PA substitutions by type and subtype of influenza virus from patients treated with baloxavir marboxil

Secondary objectives 4

1. Part A (Surveillance) To evaluate the virologic characteristics of circulating and post-treatment viruses in patients treated with baloxavir marboxil
2. Part A (Surveillance) To further evaluate the safety of a single dose of baloxavir marboxil by assessing the frequency, severity and timing of adverse events
3. Part B (Transmission) To evaluate the incidence of influenza A or B virus transmission from an otherwise healthy Index Patient treated (OwH IP) (3 weeks to < 5 years and 5 to < 12 years) treated with baloxavir marboxil to Household contacts (HHC)
4. Part B (Transmission) To evaluate the incidence of influenza A or B virus transmission resulting in symptoms from an OwH IP (3 weeks to < 5 years and 5 to <12 years) treated with baloxavir marboxil to HHC

Conditions and MedDRA coding

Influenza

Study design 1 period

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002440-PIP01-18

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Part A (Surveillance) Patients with symptoms suggestive of influenza based on investigator's judgement with diagnosis confirmed by a positive local influenza test [rapid influenza diagnostic test (RIDT), or Liat®, or polymerase chain react (PCR); for European Union (EU) sites, the test must be in compliance with In Vitro Diagnostic Regulation (IVDR)] within 24 hours before full study screening
2. Part A (Surveillance) Patients with a negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test (rapid diagnostic test, or Liat®, or PCR; for E.U. sites, the test must be in compliance with IVDR) within 48 hours before full study screening
3. Part A (Surveillance) The time interval of 48 hours or less between the onset of influenza symptoms and the start of pre-dose examinations at screening
4. Part A (Surveillance) Patients or their parents/caregivers who are able to understand the study and comply with all study procedures, and willing to provide written informed consent/assent prior to the pre-dose examinations appropriately

Exclusion criteria 6

1. Part A (Surveillance) Patients with severe influenza virus infection requiring inpatient treatment
2. Part A (Surveillance) Severely immunocompromised patients [including patients receiving immunosuppressant therapy, or those with cancer or human immunodeficiency virus (HIV) infection] as defined by the investigator
3. Part A (Surveillance) Patients with concurrent (non-influenza) infections requiring systemic anti-microbial and/or anti-viral therapy at the pre-dose examinations
4. Part A (Surveillance) Treatment with baloxavir marboxil, peramivir, laninamivir, oseltamivir, zanamivir, rimantadine, umifenovir or amantadine within 30 days prior to screening
5. Part A (Surveillance) Treatment with an investigational influenza-specific monoclonal antibody within 6 months or 5 half-lives whichever is longer and/or an investigational therapy within 30 days or 5 half-lives, whichever is longer, prior to screening
6. Part A (Surveillance) Known hypersensitivity to baloxavir marboxil or the drug product excipients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part A (Surveillance) 1. Incidence of resistance-associated pre-treatment substitutions determined at baseline (Day 1)
2. Part A (Surveillance) 2. Incidence of resistance-associated treatment-emergent substitutions based on sampling on Days 4, 6 and 10

Secondary endpoints 11

1. Part A (Surveillance) 1. Incidence of resistance-associated treatment-emergent substitutions by age groups (< 5 years [also < 1 year, ≥ 1 year to < 5 years], and 5 to < 12 years)
2. Part A (Surveillance) 2. Incidence of novel treatment-emergent mutations in PA
3. Part A (Surveillance) 3. Incidence of resistance-associated treatment-emergent substitutions by baseline vaccination status of patient (vaccinated vs not vaccinated in the last 6 months)
4. Part A (Surveillance) 4. Incidence of influenza virus type (A or B) and subtype (A/H1 or A/H3) in participants by study period
5. Part A (Surveillance) 5. Viral titers by quantitative reverse transcriptase-polymerase chain react (RT-PCR) at baseline and post-baseline timepoints
6. Part A (Surveillance) 6. The susceptibility to baloxavir marboxil by phenotyping of virus with novel PA substitutions
7. Part A (Surveillance) 7. Incidence and severity of adverse events, serious adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
8. Part B (Transmission) 8. Incidence of transmission of influenza virus by Day 6 confirmed by central RT-PCR, with virus subtype consistent with the IP.
9. Part B (Transmission) 9. Incidence of transmission of influenza virus by Day 10 confirmed by central RT-PCR, with virus subtype consistent with the IP.
10. Part B (Transmission) 10. Incidence of influenza transmission to HHC by Day 6, confirmed by RT-PCR with a virus subtype matching the IP. Transmission is defined as: • For ≥ 12 year olds: Fever (38.0 C or higher) and one respiratory symptom, OR one respiratory and one systemic symptom. • For <12 year olds: Fever (38.0 C or higher) and signs of an upper respiratory tract infection.
11. Part B (Transmission) 11. Incidence of influenza transmission to HHC by Day 10, confirmed by RT-PCR with a virus subtype matching the index patient. Transmission is defined as: For ≥ 12 year old: Fever (38.0 C or higher) and one respiratory symptom, OR one respiratory and one systemic symptom. For <12 year old: Fever (38.0 C or higher) and signs of an upper respiratory tract infection.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 7

Locations

3 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 72 files

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

Application history

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