A Study to Assess the Effect of ELX/TEZ/IVA on Glucose Tolerance in Participants With Cystic Fibrosis (CF)

Cystic Fibrosis Clinical Trial

Official title:

A Phase 3b Open-label Study to Assess the Effect of Elexacaftor (ELX)/Tezacaftor (TEZ)/Ivacaftor (IVA) on Glucose Tolerance in Cystic Fibrosis Subjects With Abnormal Glucose Metabolism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04599465
• Other study ID #: VX19-445-117
• Secondary ID: 2020-003170-44
• Status: Completed
• Phase: Phase 3
• Start date: January 15, 2021
• Est. completion date: July 14, 2022

Study information

• Verified date: July 2023
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study was evaluate the effect of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) on glucose tolerance in CF participants, 12 years of age and older who are heterozygous for the F508del mutation and a minimal function mutation (F/MF genotypes), with abnormal glucose metabolism.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: July 14, 2022
• Est. primary completion date: July 14, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Key Inclusion Criteria:

• Heterozygous for F508del and an MF mutation (F/MF genotypes)

• Forced expiratory volume in 1 second (FEV1) value = 30% of predicted mean for age, sex, and height

• Abnormal glucose tolerance determined by an OGTT as either:

• Impaired glucose tolerance (IGT) defined as 2 hour post OGTT blood glucose level =140 to <200 mg/dL (=7.77 to <11.10 mmol/L) and fasting blood glucose level <126 mg/dL (<7.00 mmol/L)

• CF-related diabetes (CFRD) defined as either fasting hyperglycemia (blood glucose level =126 mg/dL [=7.00 mmol/L] after an 8-hour fast) or 2-hour post OGTT blood glucose level =200 mg/dL (=11.10 mmol/L)

Key Exclusion Criteria:

• Clinically significant liver cirrhosis with or without portal hypertension

• Solid organ or hematological transplantation

• Lung infection with organisms associated with a more rapid decline in pulmonary status

• Type 1 or Type 2 diabetes

• Duration of CFRD =5 years

Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• ELX/TEZ/IVA
Fixed dose combination (FDC) tablets for oral administration.
• IVA
Tablets for oral administration.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	The Prince Charles Hospital	Chermside
Australia	Alfred Hospital	Melbourne
Australia	Telethon Kids Institute	Nedlands
Australia	The Royal Children's Hospital	Parkville, VIC
Australia	Sydney Children's Hospital	Randwick
Australia	Mater Adult Hospital	South Brisbane
Australia	Queensland Children's Hospital	South Brisbane
Australia	Westmead Hospital	Westmead
Belgium	Cliniques Universitaires de Bruxelles Hopital Erasme	Brussels
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven
Czechia	Klinika Nemoci Plicnich a Tuberkulozy	Brno
Czechia	Fakultni nemocnice v Motole	Praha 5
France	Centre Hospitalier Intercommunal Creteil	Créteil
France	CHRU de Lille - Hopital Albert Calmette	Lille
France	CHU Marseille - Hopital Nord	Marseille
France	Hopital Arnaud de Villeneuve	Montpellier Cedex 5
France	Centre Hospitalier Universitaire De Nantes - G. R. Laennec	Nantes
France	Centre Hospitalier Universitaire (CHU) de Nice - Hopital Pasteur	Nice
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
France	CHU de Rouen - Hopital Charles Nicolle	Rouen Cedex, Seine Maritime
France	Hopitaux Universitaires de Strasbourg	Strasbourg
France	Hopital Foch (Suresnes), Hopital Foch, Adultes	Suresnes
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona	Ancona
Italy	IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico	Genova
Italy	Azienda Ospedaliera Universitaria Policlinico G. Martino	Messina
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliero Universitaria Federico II Napoli	Naples
Italy	Azienda Ospedaliera di Verona - Ospedale Civile Maggiore	Verona
Netherlands	Academisch Medisch Centrum (Academic Medical Centre)	Amsterdam
Netherlands	HagaZiekenhuis van den Haag	Den Haag
Netherlands	University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis	Heidelberglaan
Netherlands	Erasmus Medical Center	Rotterdam
Spain	Hospital Saint Joan de Deu	Barcelona
Spain	Hospital Universitari Vall d Hebron	Barcelona
Spain	Hospital Universitari Vall d´Hebron Servicio de Broncoscopia	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Virgen de la Arrixaca	Murcia
Spain	Hospital Universitario Virgen del Rocio	Sevilla

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

Australia,  Belgium,  Czechia,  France,  Italy,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in 2-hour Blood Glucose Levels Following an OGTT to the Average of Week 36 and Week 48	Baseline 2-hour post-OGTT blood glucose level was defined as the average of valid pre-dose measurements at screening and Day 1. OGTT results were considered valid only when the participant was fasting for at least 8 hours.	Baseline, Week 36 and 48
Secondary	Percentage of Participants With Improvement in Dysglycemia Categorization at Week 48	Baseline dysglycemia category was defined as the most recent non-missing measurement before the first dose of study drug in the treatment period. Improvement in dysglycemia is a change from cystic fibrosis-related diabetes (CFRD) at baseline to impaired glucose tolerance (IGT)/normal glucose tolerance (NGT) at Week 48 OR change from IGT at baseline to NGT at Week 48. CFRD: 2-hour post-OGTT blood glucose level =200 mg/dL or fasting blood glucose level =126 mg/dL; IGT: 2-hour post-OGTT blood glucose level =140 to <200 mg/dL and fasting blood glucose level <126 mg/dL; NGT: 2 hour post-OGTT blood glucose level <140 mg/dL and fasting blood glucose level <126 mg/dL.	Baseline, Week 48
Secondary	Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		Day 1 up to Week 52