SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT00909532

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of VX-770 in Subjects With Cystic Fibrosis and the G551D Mutation

The purpose of this study was to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis aged 12 years and older who have the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Ivacaftor is a potent and selective CFTR potentiator of wild-type, G551D, F508del, and R117H forms of human CFTR protein. Potentiators are pharmacological agents that increase the chloride ion transport properties of the channel in the presence of cyclic AMP-dependent protein kinase A (PKA) activation.

NCT00909532 Cystic Fibrosis
MeSH: Fibrosis Cystic Fibrosis

2 Interventions

Name: Ivacaftor

Description: 150-mg tablets given orally q12h for up to 48 weeks

Type: Drug

150 mg Ivacaftor q12h

Name: Placebo

Description: Tablet given orally q12h for up to 48 weeks

Type: Drug

Placebo


Primary Outcomes

Description: Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.

Measure: Absolute Mean Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24

Time: baseline through 24 weeks

Secondary Outcomes

Description: Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.

Measure: Absolute Mean Change From Baseline in Percent Predicted FEV1 Through Week 48

Time: baseline through 48 weeks

Description: The CFQ-R is a health-related quality of life measure for subjects with cystic fibrosis. Each domain is scored from 0 (worst) to 100 (best). A difference of at least 4 points in the respiratory domain score of the CFQ-R is considered a minimal clinically important difference (MCID).

Measure: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score Through Week 24 and Week 48 (Respiratory Domain Score, Pooled)

Time: baseline through 24 weeks and 48 weeks

Description: The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for cystic fibrosis (CF), serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity.

Measure: Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48

Time: baseline through 24 weeks and 48 weeks

Description: Pulmonary exacerbation was defined as a change in antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of signs/symptoms such as change in sputum; new or increased hemoptysis; increased cough or dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees C; anorexia or weight loss; sinus pain/tenderness and discharge; change in physical examination of the chest; decreased pulmonary function by 10%; and radiographic changes indicative of pulmonary infection.

Measure: Time-to-first Pulmonary Exacerbation Through Week 24 and Week 48

Time: baseline through 24 weeks and 48 weeks

Description: As malnutrition is common in patients with cystic fibrosis (CF) because of increased energy expenditures due to lung disease and fat malabsorption, body weight is an important clinical measure of nutritional status.

Measure: Absolute Change From Baseline in Weight at Week 24 and Week 48

Time: baseline to 24 weeks and 48 weeks

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There are 2 SNPs

SNPs


1 G551D

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of VX-770 in Subjects With Cystic Fibrosis and the G551D Mutation. --- G551D ---

Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older With the G551D Mutation The purpose of this study was to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis aged 12 years and older who have the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. --- G551D ---

Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older With the G551D Mutation The purpose of this study was to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis aged 12 years and older who have the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. --- G551D --- --- G551D ---

Ivacaftor is a potent and selective CFTR potentiator of wild-type, G551D, F508del, and R117H forms of human CFTR protein. --- G551D ---

As malnutrition is common in patients with cystic fibrosis (CF) because of increased energy expenditures due to lung disease and fat malabsorption, body weight is an important clinical measure of nutritional status.. Inclusion Criteria: - Confirmed diagnosis of cystic fibrosis (CF) and G551D mutation in at least 1 allele - Forced expiratory volume in 1 second (FEV1) of 40% to 90% (inclusive) of predicted normal for age, gender, and height at Screening. --- G551D ---

- No clinically significant abnormalities that would have interfered with the study assessments, as judged by the investigator - Willing to use highly effective birth control methods during the study Exclusion Criteria: - History of any illness or condition that might confound the results of the study or pose an additional risk in administering study drug to the subject - Acute respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks of Day 1 of the study - History of alcohol, medication or illicit drug abuse within one year prior to Day 1 - Abnormal liver function ≥ 3x the upper limit of normal - Abnormal renal function at Screening - History of solid organ or hematological transplantation - Pregnant, planning a pregnancy, breast-feeding, or unwilling to follow contraception requirements - Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days prior to Screening - Use of inhaled hypertonic saline treatment - Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP 3A4) Inclusion Criteria: - Confirmed diagnosis of cystic fibrosis (CF) and G551D mutation in at least 1 allele - Forced expiratory volume in 1 second (FEV1) of 40% to 90% (inclusive) of predicted normal for age, gender, and height at Screening. --- G551D ---

- No clinically significant abnormalities that would have interfered with the study assessments, as judged by the investigator - Willing to use highly effective birth control methods during the study Exclusion Criteria: - History of any illness or condition that might confound the results of the study or pose an additional risk in administering study drug to the subject - Acute respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks of Day 1 of the study - History of alcohol, medication or illicit drug abuse within one year prior to Day 1 - Abnormal liver function ≥ 3x the upper limit of normal - Abnormal renal function at Screening - History of solid organ or hematological transplantation - Pregnant, planning a pregnancy, breast-feeding, or unwilling to follow contraception requirements - Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days prior to Screening - Use of inhaled hypertonic saline treatment - Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP 3A4) Cystic Fibrosis Fibrosis Cystic Fibrosis This was a phase 3 study in subjects with cystic fibrosis (CF) age 12 years and older who have a G551D-CFTR mutation and percent predicted forced expiratory volumn in 1 second (FEV1) between 40% and 90%. --- G551D ---

Patients with the G551D mutation were the targeted population for this study because ivacaftor is a potentiator of the gating function of the CFTR protein, and the most prevalent mutation with a gating defect in CF is the G551D mutation. --- G551D ---

Patients with the G551D mutation were the targeted population for this study because ivacaftor is a potentiator of the gating function of the CFTR protein, and the most prevalent mutation with a gating defect in CF is the G551D mutation. --- G551D --- --- G551D ---

This study was designed to further evaluate the efficacy of ivacaftor in subjects with CF who have a G551D-CFTR gene mutation and to evaluate safety in this population over a longer period than previously studied. --- G551D ---


2 R117H

Ivacaftor is a potent and selective CFTR potentiator of wild-type, G551D, F508del, and R117H forms of human CFTR protein. --- G551D --- --- R117H ---



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