A Study to Explore the Impact of Lumacaftor/Ivacaftor on Disease Progression in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del

NCT03625466 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: VX16-809-1212017-003761-99
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 5

Brief Summary

This study will explore the impact of lumacaftor/ivacaftor (LUM/IVA) on disease progression in subjects aged 2 through 5 years with cystic fibrosis (CF), homozygous for F508del (F/F).

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Part 1: Absolute Change From Baseline in MRI Global Chest Score at Week 48

  MRI scans assessed semi-quantitatively via a standardized chest MRI scoring system. Each participant had 6 lobes scored using 7 scoring parameters:1) Bronchiectasis/wall thickening 2) Mucus plugging 3) Abscesses/sacculations 4) Consolidations 5) Special findings 6)Mosaic pattern 7) Perfusion abnormalities. For each of 7 parameter, there were scores of 6 lobes (score of each lobe : 0= normal value, 1 = \<50% of lobe involved and 2 = \>=50% of lobe involved). MRI global score was calculated as sum of parameters 1 to 7. MRI total score is ranged from 0-84. Higher score indicate more lobe involvement.

  From Baseline at Week 48

Secondary Outcomes (4)

• Part 1: Absolute Change in Lung Clearance Index2.5 (LCI2.5) Through Week 48

  From Baseline Through Week 48

• Part 1: Absolute Change in Weight-for-age Z-score at Week 48

  From Baseline at Week 48

• Part 1: Absolute Change in Stature-for-age Z-score at Week 48

  From Baseline at Week 48

• Part 1: Absolute Change in Body Mass Index (BMI)-For-age Z-score at Week 48

  From Baseline at Week 48

Study Arms (3)

Part 1: Placebo

PLACEBO COMPARATOR

Participants received placebo matched to LUM/IVA in placebo-controlled period for 48 weeks.

Drug: Placebo

Part 1: LUM/IVA

EXPERIMENTAL

Participants weighing less than (\<)14 kilograms (kg) at screening received LUM 100 milligrams (mg)/IVA 125 mg fixed-dose combination (FDC) every 12 hours (q12h) in placebo-controlled period for 48 weeks. Participants weighing greater than or equals to (\>=)14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h in placebo-controlled period for 48 weeks.

Drug: LUM/IVA

Part 2: Overall LUM/IVA

EXPERIMENTAL

Participants who received either placebo or LUM/IVA in placebo-controlled period administered LUM/IVA (either LUM 100 mg/IVA 125 mg FDC q12h or LUM 150 mg/IVA 188 mg FDC q12h as per their body weight for participants \<6 years of age at week 48 and LUM 200 mg/IVA 250 mg FDC q12h regardless of their body weight for participants \>=6 years of age at week 48) in open-label period for 48 weeks.

Drug: LUM/IVA

Interventions

LUM/IVA DRUG

FDC tablets or granules for oral administration.

Also known as: Lumacaftor/Ivacaftor, VX-809/VX-770

Part 2: Overall LUM/IVA

Placebo DRUG

Placebo matched to LUM/IVA for oral administration.

Part 1: Placebo

Eligibility Criteria

• Age: 2 Years - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subjects with confirmed diagnosis of CF.
• Homozygous for F508del (F/F).
• Subjects who weigh ≥8 kg without shoes and wearing light clothing at the Screening Visit.

You may not qualify if:

• Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject.
• Solid organ or hematological transplantation.
• History of any illness or comorbidity reviewed at the Screening Visit that, in the opinion of the investigator, might confound the results of the study.

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (5)

Charite Paediatric Pulmonology Department

Berlin, Germany

Location

Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin

Giessen, Germany

Location

Hannover Medical School

Hanover, Germany

Location

Heidelberg Cystic Fibrosis Center

Heidelberg, Germany

Location

Universitatsklinikum Schleswig-Holstein, Klinik für Kinder- und Jugendmedizin

Lübeck, Germany

Location

Related Publications (2)

• Stahl M, Roehmel J, Eichinger M, Doellinger F, Naehrlich L, Kopp MV, Dittrich AM, Sommerburg O, Ray P, Maniktala A, Xu T, Conner S, Joshi A, Mascia M, Wielputz MO, Mall MA. Long-Term Impact of Lumacaftor/Ivacaftor Treatment on Cystic Fibrosis Disease Progression in Children 2-5 Years of Age Homozygous for F508del-CFTR: A Phase 2, Open-Label Clinical Trial. Ann Am Thorac Soc. 2024 Nov;21(11):1550-1559. doi: 10.1513/AnnalsATS.202402-201OC.

  PMID: 39173175 DERIVED

• Stahl M, Roehmel J, Eichinger M, Doellinger F, Naehrlich L, Kopp MV, Dittrich AM, Lee C, Sommerburg O, Tian S, Xu T, Wu P, Joshi A, Ray P, Duncan ME, Wielputz MO, Mall MA. Effects of Lumacaftor/Ivacaftor on Cystic Fibrosis Disease Progression in Children 2 through 5 Years of Age Homozygous for F508del-CFTR: A Phase 2 Placebo-controlled Clinical Trial. Ann Am Thorac Soc. 2023 Aug;20(8):1144-1155. doi: 10.1513/AnnalsATS.202208-684OC.

  PMID: 36943405 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

lumacaftor, ivacaftor drug combination

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Medical Monitor
• Organization: Vertex Pharmaceuticals Incorporated

medicalinfo@vrtx.com

617-341-6777

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blinded in Part 1, and Open label in Part 2
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2018
• First Posted: August 10, 2018
• Study Start: August 10, 2018
• Primary Completion: October 9, 2020
• Study Completion: October 7, 2021
• Last Updated: November 2, 2022
• Results First Posted: December 8, 2021

Record last verified: 2022-10

Locations

DE (5)