Evaluation of ELX/TEZ/IVA in Cystic Fibrosis Subjects 12 to Less Than 24 Months of Age

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vertex Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

16 Jul 2024 → 4 Sep 2025

Decision date (initial)

2024-01-24

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Vertex Pharmaceuticals Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacodynamic, Pharmacokinetic, Safety, Efficacy

To evaluate the safety and tolerability of ELX/TEZ/IVA

Secondary objectives 3

1. To evaluate the PK of ELX, TEZ, IVA, and relevant metabolites
2. To evaluate the pharmacodynamics (PD) of ELX/TEZ/IVA
3. To evaluate the efficacy of ELX/TEZ/IVA

Conditions and MedDRA coding

Cystic Fibrosis

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002324-PIP01-17

Plan to share IPD

No

IPD plan description

Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Subject’s legally appointed and authorized representative (e.g., parent or legal guardian) will sign and date an informed consent form (ICF).
2. Subjects (male and female) 12 to <24 months of age on Day 1.
3. Confirmed diagnosis of CF as determined by the investigator.
4. Subjects who have at least one F508del mutation in the CFTR gene or another ELX/TEZ/IVA-responsive CFTR mutation. A previous CFTR genotype laboratory report may be used to establish eligibility, but the subject’s genotype must be approved by the Vertex medical monitor. • All subjects will have a central laboratory genotype obtained on Day 1 (Parts A and B). Subjects with a historical CFTR genotype report may initiate study drug dosing before confirmation on central laboratory testing. Subjects who do not have a historical CFTR genotype report available will have genotyping performed at Screening Visit 1 instead of Day 1 in the respective Part, and the eligible CFTR mutation must be confirmed by central laboratory testing before the first dose of study drug. This assessment does not need to be repeated in the case of rescreening or for confirmed subjects in Part A who wish to screen for participation in Part B. • Subjects who have been enrolled based on a historical CFTR genotype laboratory report and whose central laboratory genotype does not confirm study eligibility must be discontinued from the study.
5. Subjects with stable CF disease at the start of the Treatment Period as deemed by the investigator.
6. Subjects whose parent or legal guardian is willing to keep the subject on a stable CF medication regimen (other than CFTR modulators) through Week 24 (Part B) or, if applicable, through the Safety Follow-up Visit.
7. As judged by the investigator, the parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions, and the parent or legal guardian should be able to ensure that the subject will comply with and is likely to complete the study as planned.

Exclusion criteria 11

1. History of any illness or any clinical condition that, in the opinion of the investigator, might either confound the results of the study or pose an additional risk in administering study drug(s) to the subject. This includes, but is not limited to, the following: o Clinically significant cirrhosis with or without portal hypertension o Solid organ or hematological transplantation o Cancer o Any history of seizure
2. Any clinically significant laboratory abnormalities at the Screening Visits that would interfere with the study assessments or pose an undue risk for the subject (as deemed by the investigator).
3. Any of the following abnormal laboratory values at screening: o Hemoglobin <10 g/dL o Total bilirubin, aspartate transaminase (AST), or alanine transaminase (ALT) ≥2 × upper limit of normal (ULN) o Alkaline phosphatase (ALP) or gamma-glutamyl transferase (GGT) ≥3 × ULN o Abnormal renal function defined as glomerular filtration rate ≤45 mL/min/1.73 m2 (calculated by the Bedside Schwartz equation)
4. Any history of elevated serum ALT or AST ≥3 × ULN or total bilirubin ≥2 × ULN, unless occurring before 3 months of corrected gestational age and due to an identified proximate cause, such as reversible post-hepatic biliary obstruction, meconium ileus, infection, or neonatal hyperbilirubinemia, in the judgment of the investigator.
5. An acute upper or lower respiratory infection, PEx, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug).
6. Any history of respiratory tract culture positive for an organism associated with more rapid decline in pulmonary status (including, but not limited to, Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus)
7. An acute illness not related to CF (e.g., gastroenteritis) within 14 days before the first dose of study drug (Day 1).
8. Ongoing or prior participation in an investigational drug study (including studies investigating ELX with or without coadministration with other study drugs) within 28 days of Screening Visit 1 (or the concurrent Screening Visit 1 and 2, as applicable). o A washout period of 5 terminal half lives of the previous investigational study drug, or 28 days, whichever is longer, must elapse before the Screening Visit. o The duration of the elapsed time may be longer if required by local regulations. Note: Ongoing participation in a noninterventional study (including observational studies) is permitted.
9. Ongoing breastfeeding (or consumption of expressed breastmilk) by a subject whose mother is taking any CFTR modulator. o If a mother chooses to stop their own CFTR modulator use, or to stop breastfeeding (and all other routes of feeding expressed breastmilk to the subject), so as to allow the subject to participate in this study, then a washout period of 28 days from last exposure must elapse before the Day 1 Visit.
10. Use of restricted medication within specified duration before the first dose of study drug as defined in the Prohibited Medications table of the Protocol.
11. A close relative of the subject is the investigator or a subinvestigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety and tolerability assessments as determined by AEs, clinical laboratory values, standard 12-lead ECGs, vital signs, and pulse oximetry

Secondary endpoints 2

1. PK parameters of ELX, TEZ, IVA, and relevant metabolites
2. Absolute change in sweat chloride (SwCl) from baseline through Week 24

Investigational products

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

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vertex Pharmaceuticals Inc.

Sponsor organisation

Vertex Pharmaceuticals Inc.

Address

50 Northern Avenue

City

Boston

Postcode

02210-1862

Country

United States

Scientific contact point

Organisation

Vertex Pharmaceuticals Inc.

Contact name

Clinical Trials and Medical Info

Public contact point

Organisation

Vertex Pharmaceuticals Inc.

Contact name

Clinical Trials and Medical Info

Locations

3 EU/EEA countries · 5 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 37 files

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

Application history

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