SNPMiner Trials (Home Page)
Report for Mutation L206W
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 3 clinical trials
Clinical Trials
1 A Pilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis, Residual CFTR Function, and FEV1 ≥40% Predicted
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 Cystic Fibrosis Drug: Ivacaftor 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 --- --- D579G --- --- S945L --- --- L206W ---
Primary Outcomes
Description: 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).
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 Time: 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
Description: LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment. 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).
Measure: Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment Time: Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)Description: 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 overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Measure: Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57 Time: Open-label Baseline, Open-label Day 57Description: LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Measure: Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57 Time: Open-label Baseline, Open-label Day 57Description: Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Measure: Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57 Time: Study Baseline, Open-label Day 57Description: Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Measure: Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57 Time: Open-label Baseline, Open-label Day 57Description: Adverse events (AEs) that started (or increased in severity) from first dose of study drug through completion of Follow-up were considered TEAEs, with exception that if an AE started during a Washout Period and was beyond 14 days from last dose date of preceding cycle, AE was considered as a "Washout Period" AE, and hence not TEAE. A TEAE was attributed to treatment in which it started or to the treatment in second cycling period of previous Crossover Period if it started during a Washout Period. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Data was to be reported by drug treatment for double-blind crossover period (Cycle 1 up to Washout Period 2) and open-label period.
Measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Time: From first dose of study drug through completion of follow-up visit (up to 26 weeks)2 Nutritional Impact of Ivacaftor Treatment in 6 Month to 2 Year Old Children With CF Gating Mutations
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 Cystic Fibrosis 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 ---
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 ---
Primary Outcomes
Description: Investigators will examine the effects of 12 weeks of Ivacaftor treatment on subject's SEE. Using indirect calorimetry, SEE will be assessed using a computerized metabolic cart Vmax ENCORE at each protocol visit while the child is asleep. SEE will be assessed in the morning if possible and careful note of previous feeding of the child, including the time of day, amount of food, and feeding interval prior to test
Measure: Sleeping Energy Expenditure Time: 12 WeeksDescription: Investigators will examine the effects of 12 weeks of Ivacaftor treatment on subject's BMI. Investigators will compare the results to BMI Z scores over 12 weeks compared to baseline.
Measure: Anthropometric Assessment Time: 12 WeeksSecondary Outcomes
Description: Investigators will examine the effects of 12 weeks of Ivacaftor treatment on subject's pancreatic function. Pancreatic function will be assessed at two visits by obtaining spot stool samples with fecal elastase 1. The concentration of fecal elastase I is indicative of pancreatic function.
Measure: Fecal Elastase I/Pancreatic Function Time: 12 WeeksDescription: Investigators will examine the effects of 12 weeks of Ivacaftor treatment on subject's gut health and function. Spot stool samples will be obtained to determine fecal calprotectin, a marker for gut inflammation.
Measure: Fecal Calprotectin/Gut Inflammation Time: 12 WeeksDescription: Investigators will examine the effects of 12 weeks of Ivacaftor treatment on subject's dietary fat absorption. A total plasma fatty acid panel will be assessed to measure the change in status of 22 fatty acids, the concentration of plasma fatty acids is indicative of dietary fat absorption.
Measure: Plasma Total Fatty Acids: Time: 4 to 6 monthsOther Outcomes
Description: Three day weighed food record will be obtained and to determine changes in dietary caloric intake and micro and macronutrient intake over the course of 12 weeks on ivacaftor treatment. The weighed food in grams will be used to determine the calories consumed, as well as calories from fat. The caloric intake will be used to determine micro and macro nutrient intake.
Measure: Dietary Intake Time: 12 WeeksDescription: Investigators will examine the changes in serum vitamin A, E, D and K concentrations after 12 weeks of Ivacaftor treatment. Additionally, investigators will examine the changes in total serum bile acids concentration and 14 bile acid species. Additionally, serum calprotectin will be obtained as a marker of lung and gut inflammation.
Measure: Serum fat soluble vitamins A, D, E and K, bile acids, and serum calprotectin Time: 12 WeeksDescription: Investigators will measure body composition to determine muscle and fat store changes over the course of 12 weeks on ivacaftor treatment compared to baseline.
Measure: Muscle/Fat Stores Time: 12 WeeksDescription: Investigators will observe the changes in growth status/growth velocity. This will be assessed amongst three different measurements- length (cm), weight (kg) and head circumference (cm). 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.
Measure: Growth Status/Growth Velocity Time: 12 Weeks3 Response to CFTR-modulators in Intestinal Organoids of Patients With CF Having at Least One R334W Mutation
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 Cystic Fibrosis 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 ---
Primary Outcomes
Description: Response to tezacaftor+ivacaftor in the Forskolin Induced Swelling (FIS) assay in rectal organoids
Measure: Response to CFTR-modulator in Intestinal Organoids: Increase in Forskolin induced swelling by addition of tezacaftor+ivacaftor after stimulation with Forskolin (0.8 µmol/L) Time: At study completion (when rectal biopsy is performed or when organoids are retrieved from the biobank and FIS has been performed), an average of 2 months