Phase 2
Completed N=76
A Study Evaluating the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis
Source: ClinicalTrials.gov NCT02951195 ↗Enrolled (actual)
76
Serious AEs
4.0%
Results posted
Jan 2021
Primary outcomePrimary: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) — 8; 3; 7; 10 participants
Summary
This is a Phase 2, randomized, double blind, placebo and active-controlled, parallel group, multicenter study designed to evaluate the safety and tolerability of VX-152 in Triple Combination (TC) with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF), or who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F508del/F508del).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
8; 3; 7; 10; 3; 6 | — |
| PRIMARY Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A |
-0.8; 5.7; 9.7; 8.0; -1.0; 7.3 | 0.0207 sig |
| PRIMARY Absolute Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B |
-2.2; 6.5 | 0.0007 sig |
| SECONDARY Absolute Change in Sweat Chloride Concentrations at Day 15 for Part 1 and Part 2 Cohort 2A |
-0.1; -19.5; -13.6; -27.5; 3.5; -21.3 | 0.0018 sig |
| SECONDARY Absolute Change in Sweat Chloride Concentrations Through Day 29 for Part 2 Cohort 2B |
1.6; -22.3 | <0.0001 sig |
| SECONDARY Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A |
-2.3; 10.3; 19.0; 14.8; -1.4; 13.2 | 0.0166 sig |
| SECONDARY Relative Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B |
-2.0; 11.5 | 0.0012 sig |
| SECONDARY Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 15 for Part 1 and Part 2 Cohort 2A |
-7.6; 6.6; 21.8; 18.6; 5.8; 10.6 | 0.0476 sig |
| SECONDARY Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 29 for Part 2 Cohort 2B |
4.8; 16.1 | 0.0138 sig |
| SECONDARY Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA |
167; 240; 538; 355; 463; 173 | — |
Eligibility Criteria
Inclusion Criteria
- Willing and able to comply with scheduled visits, treatment pan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
- Body weight ≥35 kg.
- Sweat chloride value ≥ 60 mmol/L from test results obtained during screening.
- Subjects must have an eligible CFTR genotype:
- Cohorts 1A, 1B, 1C: Heterozygous for F508del and a minimal function mutation known or predicted not to respond to TEZ and/or IVA.
- Cohorts 2A, 2B: Homozygous for F508del.
- Subjects must have an FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height at the Screening Visit.
- Stable CF disease as judged by the investigator.
- Willing to remain on a stable CF medication regimen through the planned end of treatment or if applicable the Safety Follow-up Visit.
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 in administering study drug to the subject.
- History of cirrhosis with portal hypertension.
- Risk factors for Torsade de Pointes.
- History of hemolysis.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.
- Clinically significant abnormal laboratory values at screening.
- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before the first dose of study drug.
- Lung infection with organisms associated with a more rapid decline in pulmonary status.
- An acute illness not related to CF within 14 days before the first dose of study drug.
- A standard digital ECG demonstrating QTc >450 msec at screening.
- History of solid organ or hematological transplantation.
- History or evidence of cataract or lens opacity determined to be clinically significant by the ophthalmologist or optometrist, based on the ophthalmologic examination during the Screening Period.
- History of alcohol or drug abuse in the past year, including but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator.
- Ongoing or prior participation in an investigational drug study with certain exceptions.
- Use of commercially available CFTR modulator within 14 days before screening (applies only to Cohorts 1A, 1B, and 1C).
- Pregnant or nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1.
Data sourced from ClinicalTrials.gov (NCT02951195). 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.