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

Phase 3
Completed
Conditions
Cystic Fibrosis
Interventions
Registration Number
NCT04599465
Lead Sponsor
Vertex Pharmaceuticals Incorporated
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
69
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
ELX/TEZ/IVAIVAParticipants received ELX 200 mg /TEZ 100 mg /IVA 150 mg in the morning and IVA 150 mg in the evening.
ELX/TEZ/IVAELX/TEZ/IVAParticipants received ELX 200 mg /TEZ 100 mg /IVA 150 mg in the morning and IVA 150 mg in the evening.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in 2-hour Blood Glucose Levels Following an OGTT to the Average of Week 36 and Week 48Baseline, Week 36 and 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.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Improvement in Dysglycemia Categorization at Week 48Baseline, 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.

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

Trial Locations

Locations (41)

Hopital Arnaud de Villeneuve

🇫🇷

Montpellier Cedex 5, France

Cliniques Universitaires de Bruxelles Hopital Erasme

🇧🇪

Brussels, Belgium

Universitair Ziekenhuis Gent

🇧🇪

Gent, Belgium

CHRU de Lille - Hopital Albert Calmette

🇫🇷

Lille, France

Telethon Kids Institute

🇦🇺

Nedlands, Australia

The Royal Children's Hospital

🇦🇺

Parkville, VIC, Australia

Sydney Children's Hospital

🇦🇺

Randwick, Australia

Fakultni nemocnice v Motole

🇨🇿

Praha 5, Czechia

Westmead Hospital

🇦🇺

Westmead, Australia

University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis

🇳🇱

Heidelberglaan, Netherlands

Hospital Universitari Vall d´Hebron Servicio de Broncoscopia

🇪🇸

Barcelona, Spain

CHU Marseille - Hopital Nord

🇫🇷

Marseille, France

Azienda Ospedaliera di Verona - Ospedale Civile Maggiore

🇮🇹

Verona, Italy

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Hospital Saint Joan de Deu

🇪🇸

Barcelona, Spain

Hospital Universitario Ramon y Cajal

🇪🇸

Madrid, Spain

Hospital Universitari Vall d Hebron

🇪🇸

Barcelona, Spain

Hospital Virgen de la Arrixaca

🇪🇸

Murcia, Spain

Hospital Universitario Virgen del Rocio

🇪🇸

Sevilla, Spain

Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg

🇧🇪

Leuven, Belgium

Azienda Ospedaliero Universitaria Federico II Napoli

🇮🇹

Naples, Italy

Centre Hospitalier Universitaire (CHU) de Nice - Hopital Pasteur

🇫🇷

Nice, France

Hopitaux Universitaires de Strasbourg

🇫🇷

Strasbourg, France

Hopital Foch (Suresnes), Hopital Foch, Adultes

🇫🇷

Suresnes, France

Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona

🇮🇹

Ancona, Italy

CHU de Rouen - Hopital Charles Nicolle

🇫🇷

Rouen Cedex, Seine Maritime, France

Erasmus Medical Center

🇳🇱

Rotterdam, Netherlands

Royal Adelaide Hospital

🇦🇺

Adelaide, Australia

The Prince Charles Hospital

🇦🇺

Chermside, Australia

Alfred Hospital

🇦🇺

Melbourne, Australia

Mater Adult Hospital

🇦🇺

South Brisbane, Australia

Queensland Children's Hospital

🇦🇺

South Brisbane, Australia

Klinika Nemoci Plicnich a Tuberkulozy

🇨🇿

Brno, Czechia

Centre Hospitalier Intercommunal Creteil

🇫🇷

Créteil, France

Centre Hospitalier Lyon Sud

🇫🇷

Pierre-Bénite, France

IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico

🇮🇹

Genova, Italy

HagaZiekenhuis van den Haag

🇳🇱

Den Haag, Netherlands

Centre Hospitalier Universitaire De Nantes - G. R. Laennec

🇫🇷

Nantes, France

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

🇮🇹

Milano, Italy

Academisch Medisch Centrum (Academic Medical Centre)

🇳🇱

Amsterdam, Netherlands

Azienda Ospedaliera Universitaria Policlinico G. Martino

🇮🇹

Messina, Italy

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