Phase 3
Completed N=1,044
A Study to Evaluate the Safety and Efficacy of Long Term Treatment With VX-661 in Combination With Ivacaftor in Participants With Cystic Fibrosis Who Have an F508del-CFTR Mutation
Source: ClinicalTrials.gov NCT02565914 ↗Enrolled (actual)
1,044
Serious AEs
31.1%
Results posted
Jun 2020
Primary outcomePrimary: Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) — 995; 351 Participants
◆ Published Evidence
Established
51citations · ~10 / year
Long-term safety and efficacy of tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years or older who are homozygous or heterozygous for Phe508del CFTR (EXTEND): an open-label extension study.
Summary
This is a Phase 3, multicenter, open-label, 3-part rollover study in subjects with CF who are homozygous or heterozygous for the F508del-CFTR mutation and who participated in studies VX13-661-103 (Study 103, NCT02070744), VX14-661-106 (Study 106, NCT02347657), VX14-661-107 (Study 107, NCT02516410), VX14-661-108 (Study 108, NCT02392234), VX14-661-109 (Study 109, NCT02412111), VX14-661-111 (Study 111, NCT02508207), VX15-661-112 (NCT02730208), and VX16-661-114 (NCT03150719). The study is designed to evaluate the safety and efficacy of long-term treatment of VX-661 in combination with ivacaftor.
Linked Publications
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Long-term safety and efficacy of tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years or older who are homozygous or heterozygous for Phe508del CFTR (EXTEND): an open-label extension study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
995; 351 | — |
| PRIMARY Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs |
427; 136 | — |
| PRIMARY Part C: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
168; 44 | — |
| SECONDARY Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set |
2.1; 2.0 | — |
| SECONDARY Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set |
4.1; 6.7; 7.5 | — |
| SECONDARY Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set |
2.7 | — |
| SECONDARY Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set |
4.1; 2.6 | — |
| SECONDARY Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set |
4.3; 4.2 | — |
| SECONDARY Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set |
7.9; 11.6; 13.0 | — |
| SECONDARY Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set |
6.4 | — |
| SECONDARY Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set |
6.1; 5.2 | — |
| SECONDARY Part A: Number of Pulmonary Exacerbation (PEx) Events for 106/110 PEx Analysis Set |
306; 423 | — |
| SECONDARY Part A: Number of Pulmonary Exacerbation (PEx) Events for 108/110 PEx Analysis Set |
89; 51; 46 | — |
| SECONDARY Part A: Absolute Change in Body Mass Index (BMI) for 106/110 Efficacy Set |
0.47; 0.38 | — |
| SECONDARY Part A: Absolute Change in Body Mass Index (BMI) for 108/110 Efficacy Set |
1.07; 0.96; 1.05 | — |
| SECONDARY Part A: Absolute Change in Body Mass Index (BMI) for 103/110 Efficacy Set |
1.38 | — |
| SECONDARY Part A: Absolute Change in Body Mass Index (BMI) for Study 111/110 Efficacy Set |
1.59; 0.26 | — |
| SECONDARY Part A: Absolute Change in BMI Z-score for 106/110 Efficacy Set |
0.10; -0.14 | — |
| SECONDARY Part A: Absolute Change in BMI Z-score for 108/110 Efficacy Set |
0.11; 0.07; 0.30 | — |
| SECONDARY Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 106/110 Efficacy Set |
1.7; 3.0 | — |
| SECONDARY Part A: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 108/110 Efficacy Set |
10.3; 11.2; 13.8 | — |
| SECONDARY Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/110 Efficacy Set |
8.6 | — |
| SECONDARY Part A: Absolute Change in Body Weight for Study 106/110 Efficacy Set |
2.0; 2.1 | — |
| SECONDARY Part A: Absolute Change in Body Weight for 108/110 Efficacy Set |
3.5; 3.5; 3.6 | — |
| SECONDARY Part A: Absolute Change in Body Weight for 103/110 Efficacy Set |
4.0 | — |
| SECONDARY Part A: Absolute Change in Body Weight for 111/110 Efficacy Set |
4.2; 0.6 | — |
| SECONDARY Part A: Absolute Change in Body Weight Z-score for 106/110 Efficacy Set |
0.07; -0.06 | — |
| SECONDARY Part A: Absolute Change in Body Weight Z-score for 108/110 Efficacy Set |
0.15; 0.09; 0.43 | — |
| SECONDARY Part A: Absolute Change in Height Z-score for 106/110 Efficacy Set |
0.01; 0.13 | — |
| SECONDARY Part A: Absolute Change in Height Z-score for 108/110 Efficacy Set |
-0.04; 0.20; 0.23 | — |
| SECONDARY Part A: Time-to-first Pulmonary Exacerbation (PEx) for 106/110 PEx Analysis Set |
0.470; 0.438 | — |
| SECONDARY Part A: Time-to-first Pulmonary Exacerbation (PEx) for 108/110 PEx Analysis Set |
0.497; 0.493; 0.639 | — |
| SECONDARY Part A: Plasma Concentrations of TEZ, TEZ Metabolite (M1-TEZ), Ivacaftor (IVA) and Ivacaftor Metabolite (M1-IVA) |
2070; 4580; 892; 1740 | — |
| SECONDARY Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) |
1.7; 8.3 | — |
| SECONDARY Part B: Absolute Change in Body Mass Index (BMI) |
0.70; 1.84 | — |
| SECONDARY Part B: Absolute Change in BMI Z-score |
-0.03; 0.21 | — |
| SECONDARY Part B: Number of Pulmonary Exacerbation (PEx) Events |
386; 94 | — |
Eligibility Criteria
Inclusion Criteria
Part A:
- Participants entering the Treatment Cohort must meet all of the following criteria:
- Elect to enroll in the Treatment Cohort
- Completed study drug Treatment Period in a parent study (NCT02070744, NCT02347657, NCT02516410, NCT02392234, NCT02412111) or study drug treatment and the Safety Follow up Visit for participants from NCT02508207.
- Willing to remain on a stable CF regimen through the Safety Follow-up Visit.
- Participants re-enrolling in the Part A Treatment Cohort must meet all of the following criteria:
- Previously received at least 4 weeks of study drug before discontinuing in Part A of Study NCT02565914 to participate in another qualified Vertex study.
- Completed the last required visit of another qualified Vertex study before or during the Returning Visit in Part A Study NCT02565914.
- Participants entering the Part A Observational Cohort must meet the following criteria:
- <18 years of age (age on the date of informed consent/assent in the parent study)
- Completed study drug Treatment Period in a parent study or study drug treatment and the Safety Follow up Visit for subjects from NCT02508207, but do not elect to enroll in the NCT02565914 Treatment Cohort; or
- Received at least 4 weeks of study drug treatment and completed visits up to the last scheduled visit of the Treatment Period of a parent study (and the Safety Follow up Visit for participants from NCT02508207), but do not meet eligibility criteria for enrollment into the Treatment Cohort
Part B:
Participants who meet all of the following inclusion criteria will be eligible for Part B.
- Did not withdraw consent from the parent study or Part A of Study NCT02565914.
- Completed study drug treatment during the Treatment Period in Part A of - Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit of Study NCT02565914.
Participants re enrolling in Part B must meet all of the following criteria:
- Previously received at least 4 weeks of study drug before discontinuing Study NCT02565914 to participate in another qualified Vertex study, which is defined as a Vertex study of investigational CFTR modulators that allows participation of participants in Study NCT02565914.
- Completed the last required visit of another qualified Vertex study before or during the Returning Visit in Part B.
- Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit in Part B.
Part C:
- Participants who meet all of the following inclusion criteria will be eligible for Part C.
- Did not withdraw consent from Part B of Study NCT02565914.
- Completed study drug treatment during Part B of NCT02565914.
- Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit of Part C.
Exclusion Criteria
- History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the subject.
- Pregnant and nursing females.
- Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements.
- History of drug intolerance in the parent study that would pose an additional risk to the subject.
- Participation in an investigational drug trial (including studies investigating VX-661/ivacaftor or lumacaftor/ivacaftor) other than the parent studies of NCT02565914 or other eligible Vertex studies investigating VX-661 in combination with ivacaftor, or use of a commercially available CFTR modulator.
Other protocol defined Inclusion/Exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT02565914) and the linked publication. 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.