Clinical trial NCT01685801: Pilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis and Residual CFTR Function
Official title: A Pilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis, Residual CFTR Function, and FEV1 ≥40% Predicted
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2012-09-14
Enrollment: 24
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study is a multiple within participant crossover study to evaluate the effect of ivacaftor on lung function in participants aged 12 years and older with cystic fibrosis (CF) who have phenotypic or molecular evidence of residual CF transmembrane conductance regulator (CFTR) function.

Detailed description: CFTR Mutations associated with residual function or defective messenger ribonucleic acid (mRNA) splicing include the following:

R117H, E56K, P67L, D110E, D110H, R117C, R347H, R352Q, A455E, D579G, S945L, L206W, R1070W, F1074L, D1152H, S1235R, D1270N, 2789+5G-\>A, 3849+10kbC-\>T, 3272-26A-\>G, 711+5G-\>A, 3120G-\>A, 1811+1.6kbA-\>G, 711+3A-\>G, 1898+3A-\>G, 1898+1G-\>A, 1717-1G-\>A, 1717-8G-\>A, 1342-2A-\>C, 405+3A-\>C, 1716G/A 1811+1G-\>C, 1898+5G-\>T, 3850-3T-\>G, IVS14b+5G-\>A, 1898+1G-\>T, 4005+2T-\>C, 621+3A-\>G, 621+1G-\>T.

Eligibility criteria: Inclusion Criteria:

* Male or female participants with confirmed diagnosis of CF
* Clinical evidence of residual CFTR function based on any 1 of the following: 1) Clinically documented residual exocrine pancreatic function, 2) Sweat chloride value less than equal to (\<=) 80 millimole per liter (mmol/L) at screening, or 3) Age of diagnosis greater than equal to (\>=) 12 years and at least 1 copy of a CFTR mutation associated with residual CFTR function or defective mRNA splicing
* FEV1 \>= 40 percent (%)
* 12 years of age or older
* Willing to agree to meet the contraception requirements
* Able to swallow tablets

Exclusion Criteria:

* A copy of any of the following CFTR mutations: G551D, G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, or G1349D
* Unable to perform spirometry
* An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1
* Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within the 30 days prior to screening

Primary outcomes:
measure: Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment
timeFrame: Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)
Secondary outcomes:
measure: Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment
timeFrame: Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)
measure: Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57
timeFrame: Open-label Baseline, Open-label Day 57
measure: Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57
timeFrame: Open-label Baseline, Open-label Day 57
measure: Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57
timeFrame: Study Baseline, Open-label Day 57
measure: Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57
timeFrame: Open-label Baseline, Open-label Day 57
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose of study drug through completion of follow-up visit (up to 26 weeks)
Other outcomes:
Locations:
city: Denver
country: United States
state: Colorado
Study officials:
affiliation: National Jewish Health
name: Jerry Nick, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nick JA, St Clair C, Jones MC, Lan L, Higgins M; VX12-770-113 Study Team. Ivacaftor in cystic fibrosis with residual function: Lung function results from an N-of-1 study. J Cyst Fibros. 2020 Jan;19(1):91-98. doi: 10.1016/j.jcf.2019.09.013. Epub 2019 Nov 26.