This study aims to assess the effects of programmed exercise combined with CFTR protein modulator drugs in the cardiorespiratory fitness, strength, functional capacity and agility in a group of young patients with Cystic Fibrosis.

NCT04415268

Conditions

1. Cystic Fibrosis in Children

Interventions

1. Behavioral: Exercise
2. Behavioral: Unsupervised exercise
3. Drug: CFTR Modulators

MeSH:Cystic Fibrosis Fibrosis

- Age 6-18 years; eligible to receive treatment with TEZ/IVA or LUM/IVA according to the AEMPS (LUM/IVA for 6-11 year-old children homozygous for the F508del mutation; TEZ/IVA for ≥ 12 year-old children homozygous for the Phe508del mutation, as well as heterozygous for the F508 mutation plus one of the following mutations: P67L, R117C, L206W, R352Q, A455E, D579G, 711 + 3A G, S945L, S977F, R1070W, D1152H, 2789 + 5G A, 3272-26A G, and 3849 + 10kbC T); - Agreement to collaborate in performing static and dynamic pulmonary function tests. --- P67L --- --- R117C --- --- L206W --- --- R352Q --- --- A455E ---

The purpose of this research study is to determine the effects of clinically prescribed ivacaftor treatment on 6-24 month old children with CF and gating mutations on sleeping energy expenditure, growth status and gut health and function.

NCT03783286

Conditions

1. Cystic Fibrosis

Interventions

1. Drug: Ivacaftor

MeSH:Cystic Fibrosis

Each value will be used to calculate the growth velocity percentile of the subjects over the course of 12 weeks on ivacaftor treatment compared to baseline.. Inclusion Criteria: - Cystic fibrosis with at least one CFTR gating mutation (E56K, G178R, S549R, S977F, F1074L, 2789+5G→A,P67L, E193K, G551D, F1052V, D1152H, 3272-26A→G, R74W, L206W, G551S, K1060T, G1244E, 3849+10kbC→T, D110E, R347H, D579G, A1067T, S1251N, D110H, R352Q, 711+3A→G, G1069R, S1255P, R117C, A455E, E831X, R1070Q, D1270N, R117H, S549N, S945L, R1070W, G1349D) approved for treatment - Age: 6-24 months of age - In their usual state of good health - A clinical decision has been made for subject to begin ivacaftor treatment - Family committed to the 4 to 6 month study protocol with visits to CHOP that will last 2 or 3 days for the baseline visit (Visit 1) prior to ivacaftor and the 12 week visit (Visit 3) after clinically prescribed ivacaftor treatment has begun, and will last 2 days for the 6 week visit (Visit 2) after ivacaftor treatment has begun. --- E56K --- --- G178R --- --- S549R --- --- S977F --- --- F1074L --- --- P67L --- --- E193K --- --- G551D --- --- F1052V --- --- D1152H --- --- R74W --- --- L206W --- --- G551S --- --- K1060T --- --- G1244E --- --- D110E --- --- R347H --- --- D579G --- --- A1067T --- --- S1251N --- --- D110H --- --- R352Q --- --- G1069R --- --- S1255P --- --- R117C --- --- A455E ---

Exclusion Criteria: - On parenteral nutrition - Use of any medications which are as inhibitors or inducers of cytochrome P450 (CYP) 3A - Liver function tests elevated above 3x the reference range for age and sex - Other illness affecting growth or nutritional status - Other contraindications described for ivacaftor therapy Inclusion Criteria: - Cystic fibrosis with at least one CFTR gating mutation (E56K, G178R, S549R, S977F, F1074L, 2789+5G→A,P67L, E193K, G551D, F1052V, D1152H, 3272-26A→G, R74W, L206W, G551S, K1060T, G1244E, 3849+10kbC→T, D110E, R347H, D579G, A1067T, S1251N, D110H, R352Q, 711+3A→G, G1069R, S1255P, R117C, A455E, E831X, R1070Q, D1270N, R117H, S549N, S945L, R1070W, G1349D) approved for treatment - Age: 6-24 months of age - In their usual state of good health - A clinical decision has been made for subject to begin ivacaftor treatment - Family committed to the 4 to 6 month study protocol with visits to CHOP that will last 2 or 3 days for the baseline visit (Visit 1) prior to ivacaftor and the 12 week visit (Visit 3) after clinically prescribed ivacaftor treatment has begun, and will last 2 days for the 6 week visit (Visit 2) after ivacaftor treatment has begun. --- E56K --- --- G178R --- --- S549R --- --- S977F --- --- F1074L --- --- P67L --- --- E193K --- --- G551D --- --- F1052V --- --- D1152H --- --- R74W --- --- L206W --- --- G551S --- --- K1060T --- --- G1244E --- --- D110E --- --- R347H --- --- D579G --- --- A1067T --- --- S1251N --- --- D110H --- --- R352Q --- --- G1069R --- --- S1255P --- --- R117C --- --- A455E ---

In contrary to what is seen in FRT cells, rectal organoids of patients with a R334W mutation do respond to CFTR modulators ivacaftor and lumacaftor. The present study will investigate the response to modulators in organoids of 30 patients with CF and a R334W mutation, to allow further stratificaton for a future clinical trial assessing the clinical effect of ivacaftor/tezacaftor in patients with CF and a R334W mutation.

NCT04254705

Conditions

1. Cystic Fibrosis

Interventions

1. Procedure: Rectal Biopsy

MeSH:Cystic Fibrosis

Exclusion Criteria: - A potential subject who meets any of the following criteria will be excluded from participation: 1. Subject has one of the following CFTR-mutations: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, R117H, P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A>G, S945L, S977F, R1070W, D1152H, 2789+5G>A, 3272 26A>G, 3849+10kbC>T 2. A history of hemorrhoids and recent rectal bleeding 3. FEV1 above 90% predicted or below 30% predicted during stable disease 4. History of lung transplantation. --- G551D --- --- G1244E --- --- G1349D --- --- G178R --- --- G551S --- --- S1251N --- --- S1255P --- --- S549N --- --- S549R --- --- R117H --- --- P67L --- --- R117C --- --- L206W --- --- R352Q --- --- A455E ---

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.

NCT01685801

Conditions

1. Cystic Fibrosis

Interventions

1. Drug: Ivacaftor
2. Drug: Placebo-matched-to-ivacaftor tablet

MeSH:Cystic Fibrosis Fibrosis

Data was to be reported by drug treatment for double-blind crossover period (Cycle 1 up to Washout Period 2) and open-label period.. 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 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 Cystic Fibrosis Cystic Fibrosis Fibrosis 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, --- G551D --- --- G178R --- --- S549N --- --- S549R --- --- G551S --- --- G970R --- --- G1244E --- --- S1251N --- --- S1255P --- --- G1349D --- --- G551D --- --- G178R --- --- S549N --- --- S549R --- --- G551S --- --- G970R --- --- G1244E --- --- S1251N --- --- S1255P --- --- G1349D --- --- R117H --- --- E56K --- --- P67L --- --- D110E --- --- D110H --- --- R117C --- --- R347H --- --- R352Q --- --- A455E ---

This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter, crossover study that will evaluate the efficacy of LUM/IVA in subjects with CF 12 years of age and older who have at least one A455E mutation.

NCT03061331

Conditions

1. Cystic Fibrosis

Interventions

1. Drug: LUM/IVA
2. Drug: Placebo

MeSH:Cystic Fibrosis Fibrosis

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Efficacy of Lumacaftor/Ivacaftor Combination Therapy in Subjects With Cystic Fibrosis Who Have an A455E-CFTR Mutation. --- A455E ---

Lumacaftor/Ivacaftor Combination Therapy in Subjects With CF Who Have an A455E CFTR Mutation This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter, crossover study that will evaluate the efficacy of LUM/IVA in subjects with CF 12 years of age and older who have at least one A455E mutation. --- A455E ---

Lumacaftor/Ivacaftor Combination Therapy in Subjects With CF Who Have an A455E CFTR Mutation This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter, crossover study that will evaluate the efficacy of LUM/IVA in subjects with CF 12 years of age and older who have at least one A455E mutation. --- A455E --- --- A455E ---

Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 8. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.. Inclusion Criteria: - Male or female with confirmed diagnosis of CF - All subjects must have an A455E mutation on at least 1 CFTR allele; no more than 10 subjects may have an F508del mutation on 1 CFTR allele. --- A455E ---

- Use of strong inhibitors or strong inducers of CYP3A, including consumption of certain herbal medications and certain fruit and fruit juices, within 14 days before Day 1 - Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements Inclusion Criteria: - Male or female with confirmed diagnosis of CF - All subjects must have an A455E mutation on at least 1 CFTR allele; no more than 10 subjects may have an F508del mutation on 1 CFTR allele. --- A455E ---