Pilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis and Residual CFTR Function

NCT01685801 | Completed Phase 2 Results

• 1 other identifier: VX12-770-113
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• 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

  FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).

  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 (6)

• Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment

  Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)

• Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57

  Open-label Baseline, Open-label Day 57

• Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57

  Open-label Baseline, Open-label Day 57

• Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57

  Study Baseline, Open-label Day 57

• Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57

  Open-label Baseline, Open-label Day 57

Study Arms (4)

Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP)

EXPERIMENTAL

During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and Cycle 2 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.

Drug: Ivacaftor; Drug: Placebo-matched-to-ivacaftor tablet

Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI)

EXPERIMENTAL

During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and Cycle 2 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.

Drug: Ivacaftor; Drug: Placebo-matched-to-ivacaftor tablet

Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP)

EXPERIMENTAL

During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and Cycle 2 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.

Drug: Ivacaftor; Drug: Placebo-matched-to-ivacaftor tablet

Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)

EXPERIMENTAL

During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and Cycle 2 \[(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)\] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.

Drug: Ivacaftor; Drug: Placebo-matched-to-ivacaftor tablet

Interventions

Ivacaftor DRUG

150 milligram (mg) tablet orally every 12 hours up to 12 weeks.

Also known as: Kalydeco, VX-770

Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP); Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI); Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP); Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)

Placebo-matched-to-ivacaftor tablet DRUG

Orally every 12 hours up to 4 weeks.

Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP); Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI); Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP); Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (%)
• years of age or older
• Willing to agree to meet the contraception requirements
• Able to swallow tablets

You may not qualify if:

• 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

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (1)

Unknown Facility

Denver, Colorado, United States

Location

Related Publications (1)

• 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.

  PMID: 31784217 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

ivacaftor

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Medical Monitor
• Organization: Vertex Pharmaceuticals Incorporated

medicalinfo@vrtx.com

617-341-6777

Study Officials

• Jerry Nick, MD

  National Jewish Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2012
• First Posted: September 14, 2012
• Study Start: September 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: May 19, 2015
• Results First Posted: May 19, 2015

Record last verified: 2015-04

Locations

US (1)