Phase 2
Completed N=190
Study of VX-661 Alone and in Combination With Ivacaftor in Subjects Homozygous or Heterozygous to the F508del-Cystic Fibrosis Transmembrane Conductance Regulator(CFTR) Mutation
Source: ClinicalTrials.gov NCT01531673 ↗Enrolled (actual)
190
Serious AEs
8.4%
Results posted
Apr 2018
Primary outcomePrimary: Safety as Determined by Adverse Events (AEs) — 30; 8; 7; 15 participants
Summary
The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) effects of VX-661 alone and when coadministered with ivacaftor in participants with cystic fibrosis (CF) who are homozygous or heterozygous for the F508del-CFTR mutation.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Safety as Determined by Adverse Events (AEs) |
30; 8; 7; 15; 7; 18 | — |
| PRIMARY Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b |
3.92; -4.76; -5.06; -20.43; -6; -6.04 | 0.0647 |
| PRIMARY Change in Sweat Chloride From Baseline Through Study Day 28 for Group 6 |
-6.07; -7.89; -1.19 | 0.0357 sig |
| PRIMARY Change in Sweat Chloride From Baseline Through Study Day 28 for Group 7 |
10.18; -7.02 | 0.0238 sig |
| SECONDARY Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b |
1.73; -3.13; -5.37; -19.48; -5.02; -6.85 | — |
| SECONDARY Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6 |
-6.61; -11.04; -0.36; -7.9; -7.11; -2.1 | — |
| SECONDARY Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7 |
4.87; -7.28; 10.75; -8.95; 9.37; -4.14 | — |
| SECONDARY Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b |
3.49; 1.63; 1.3; 1.6; 2.9; 3.75 | — |
| SECONDARY Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 |
0.94; 2.31; 1.47; 1.37; 1.95; 1.09 | — |
| SECONDARY Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7 |
1.4; 4.6; 3; 4.14; 0.98; 5.22 | — |
| SECONDARY Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b |
0.14; 0.07; 0.05; 0.04; 0.1; 0.14 | — |
| SECONDARY Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 |
0.02; 0.09; 0.07; 0.04; 0.06; 0.05 | — |
| SECONDARY Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7 |
0.09; 0.16; 0.14; 0.15; 0.08; 0.18 | — |
| SECONDARY Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b |
4.02; 5.54; 3.8; 0.61; 3.52; 5.15 | — |
| SECONDARY Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6 |
0.87; 1.91; 1.65; 2.02; 0.87; 2.78 | — |
| SECONDARY Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7 |
-3.02; 3.79; 1.83; 5.24; -7.87; 2.33 | — |
| SECONDARY Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 After Administration of VX-661 Monotherapy |
6260; 23000; 88100; 98900 | — |
| SECONDARY AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor |
8950; 26300; 82700; 138000; 77600; 73300 | — |
Eligibility Criteria
Inclusion Criteria
- Male or female with confirmed diagnosis of CF
- Must have the F508del-CFTR gene mutation in both alleles (Groups 1, 2, 3, 4, 5, 6). Group 7 participants must have the F508del-CFTR mutation on 1 allele, and gating mutation G551D on the second allele and have been on their physician prescribed 150 mg KalydecoTM q12h (commercially available ivacaftor) for at least 28 days at the Screening Visit.
- Forced expiratory volume in 1 second(FEV1) 40% to 90% (inclusive) of predicted normal for age, gender, and height (Knudson standards) at screening
- Weight >40 kg and BMI >18.5
- Participants of child-bearing potential and who are sexually active must meet the contraception requirements.
Exclusion Criteria
- History of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant.
- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Study Day 1.
- History of solid organ or hematological transplantation
- Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer) before screening
- History of alcohol, medication, or illicit drug abuse within 1 year prior to screening
- Pregnant, breast-feeding, or not willing to follow contraception requirements
Data sourced from ClinicalTrials.gov (NCT01531673). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.