Evaluation of Long-Term Safety and Efficacy of Vanzacaftor/Tezacaftor/Deutivacaftor in Cystic Fibrosis Subjects 1 Year of Age and Older

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

5 Sep 2023 → ongoing

Decision date (initial)

2023-06-19

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: Efficacy, Pharmacodynamic, Safety

To evaluate the long-term safety and tolerability of VNZ/TEZ/D-IVA

Secondary objectives 1

1. To evaluate the long-term efficacy of VNZ/TEZ/D-IVA

Conditions and MedDRA coding

Cystic Fibrosis

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003052-PIP01-21

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Subject, or subject’s legally appointed and authorized representative, will sign and date an ICF. Subject will sign an assent form.
2. As judged by the investigator, the legal representative or guardian must be able to understand protocol requirements, restrictions, and instructions and the legal representative or guardian should be able to ensure that the subject will comply with and is likely to complete the study as planned.
3. Part A: Did not withdraw consent from the parent study.
4. Part A: Meets at least 1 of the following criteria: • Completed study drug treatment in the parent study. • Had study drug interruption(s) in the parent study, but did not prematurely discontinue study drug, and completed study visits up to the last scheduled visit of the Treatment Period of the parent study.
5. Willing to remain on a stable CF treatment regimen through completion of study participation.
6. Part B (Cohort 1): Did not withdraw consent from Part A.
7. Part B (Cohort 1): Meets at least 1 of the following criteria: • Completed study drug treatment in Part A. • Had study drug interruption(s) in Part A, but did not permanently discontinue study drug, and completed study visits up to the last scheduled visit of the Treatment Period of Part A.
8. Part A (Cohort 2, Pancreatic Enzyme Replacement Therapy [PERT] sub study only): Meets all of the inclusion criteria for Part A, Did not withdraw consent from Part A, Currently receiving PERT

Exclusion criteria 8

1. History of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug(s) to the subject.
2. New development of a comorbidity during the parent study or Part A that, in the opinion of the investigator, might pose an additional risk in administering study drug to the subject. This includes, but is not limited to, the following: • Hepatic cirrhosis with portal hypertension, moderate hepatic impairment, or severe hepatic impairment that, in the opinion of the investigator, might pose an additional risk in administering study drug to the subject. •Solid organ or hematological transplantation.
3. History of drug intolerance in the parent study that would pose an additional risk to the subject in the opinion of the investigator.
4. Current participation in an investigational drug study other than the parent study. Participation in a noninterventional study, and/or screening for another Vertex study is permitted.
5. History of poor compliance with study drug and/or procedures in the parent study as deemed by the investigator.
6. The subject or 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 at that site.
7. Cohort 1 only: Pregnant or breast-feeding females. Female subjects must have a negative pregnancy test at the Part A and Part B Day 1 Visit before receiving the first dose of study drug.
8. Cohort 2, Pancreatic Enzyme Replacement Therapy [PERT] sub study only: Meets none of the exclusion criteria for Part A, History of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the sub study or pose additional risk to the subject by withdrawing PERT

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety and tolerability of long-term treatment with VNZ/TEZ/D-IVA based on adverse events (AEs), clinical laboratory values, ECGs, vital signs, and pulse oximetry

Secondary endpoints 7

1. Absolute change in SwCl
2. Absolute change in ppFEV1
3. Number of PEx and CF-related hospitalizations
4. Absolute change in CFQ-R RD score
5. Absolute change in BMI and BMI-for-age z score
6. Absolute change in weight and weight-for-age z score
7. Absolute change in height and height-for-age z score

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

4 EU/EEA countries · 8 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 122 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