A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor

Browse trials for

• Cystic Fibrosis 1,581
• Fibrosis 3,256

Keywords

• Homozygous for the F508del CFTR Mutation

Cystic Fibrosis

1,581 studies on the registry are indexed under Cystic Fibrosis; 190 are open to participants now.

This study's enrollment of 510 is above the median of 36 across 1,034 interventional studies indexed under Cystic Fibrosis.

Lead sponsor

Vertex Pharmaceuticals Incorporated is the lead sponsor of 243 studies on the registry; 19 are open to participants now.

Of its 102 completed or terminated interventional studies of FDA-regulated products, 49 (48%) have results posted.

Study arms

• Placebo comparator
  Placebo

  Placebo matched to VX-661 plus IVA FDC tablet administered orally in the morning and placebo matched to IVA tablet administered orally in the evening up to Week 24.

  Drug: VX-661 Plus Ivacaftor Combination Placebo · Drug: Ivacaftor placebo

• Experimental
  VX-661/IVA

  VX-661 100 mg plus IVA 150 mg FDC tablet administered orally in the morning and IVA 150 mg tablet administered orally in the evening up to Week 24.

  Drug: VX-661 Plus Ivacaftor Combination · Drug: Ivacaftor

Interventions

• DrugVX-661 Plus Ivacaftor Combination

  FDC tablet, oral use

• DrugIvacaftor

  Tablet, oral use

• DrugVX-661 Plus Ivacaftor Combination Placebo

  FDC tablet, oral use

• DrugIvacaftor placebo

  Tablet, oral use

Primary outcomes

1. Absolute Change From Baseline (Day 1) in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24

   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

   Time frame: Day 1, Through Week 24

Secondary outcomes

1. Relative Change From Baseline (Day 1) in ppFEV1 Through Week 24

   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

   Time frame: Day 1, Through Week 24

2. Number of Pulmonary Exacerbations Per Year

   Pulmonary exacerbation was defined as a new event or change in antibiotic therapy for greater than or equal to 4 sinopulmonary signs/symptoms. Pulmonary exacerbation events per year (48 weeks) were reported.

   Time frame: Day 1 through Week 24

3. Absolute Change From Baseline (Day 1) Body Mass Index (BMI) at Week 24

   BMI was defined as weight in kilograms (kg) divided by height in square meter (m\^2).

   Time frame: Day 1, Week 24

4. Absolute Change From Baseline (Day 1) in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 24

   The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

   Time frame: Day 1, Through Week 24

5. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

   AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Any AE that increased in severity or newly developed at or after initial dosing of study drug to Week 28 was considered treatment-emergent.

   Time frame: Day 1 up to Week 28

6. Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24

   Pulmonary exacerbation was defined as a new event or change in antibiotic therapy for greater than or equal to 4 sinopulmonary signs/symptoms. Time to event data was not collected and instead, Number of Subjects with first event were collected and are reported. Time-to-first pulmonary exacerbation was planned to be estimated using Kaplan-Meier (KM) estimates. However, due to less than 50% of events, time-to-first event data was not estimated. Instead, number of participants with at least one pulmonary exacerbation event were collected and are reported.

   Time frame: Day 1 through Week 24

7. Absolute Change From Baseline (Day 1) in Sweat Chloride Through Week 24

   Sweat samples were collected using an approved collection device.

   Time frame: Day 1, Through Week 24

8. Absolute Change From Baseline (Day 1) in BMI Z-score at Week 24 in Participants Less Than (<) 20 Years Old at the Time of Screening)

   BMI was defined as weight in kg divided by height in m\^2. z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score (BMI z-score).

   Time frame: Day 1, Week 24

9. Absolute Change From Baseline (Day 1) in Body Weight at Week 24

   Time frame: Day 1, Week 24

10. Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1 VX-661 and M2-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)

    This outcome was not planned to be assessed in Placebo arm.

    Time frame: Pre-morning dose on Week 16

Baseline characteristics

Publications

• Taylor-Cousar JL, Munck A, McKone EF, van der Ent CK, Moeller A, Simard C, Wang LT, Ingenito EP, McKee C, Lu Y, Lekstrom-Himes J, Elborn JS. Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del. N Engl J Med. 2017 Nov 23;377(21):2013-2023. doi: 10.1056/NEJMoa1709846. Epub 2017 Nov 3. PubMed 29099344 ↗

Study documents

• Study protocol · May 6, 2016
• Statistical analysis plan · Feb 9, 2017

Documents are hosted by the registry — open the source record to download them.