Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
ivacaftor · 16 trials · 3 indications
Absolute change in percent predicted in 1 second FEV1 from baseline through week 24
LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation was considered treatment-emergent.
AE: any untoward medical occurrence in a participants during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the 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. TEAEs were defined as adverse events with start date or increased severity on and after the first dose of study drug through Week 108.
AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received and for overall participants.
AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. AE includes both serious and non-serious AE. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received.
Plasma concentration was reported for ivacaftor and its metabolites (hydroxymethyl ivacaftor \[M1\] and ivacaftor carboxylate \[M6\]) up to 24 hours post-dose on Day 4 (Hour 0 \[pre-dose\] on Day 1 and Day 4; 2, 3, 6, 24 hours post-dose on Day 4). Data was planned to be reported for overall participants in the period.
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 subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 6 to 17 years and for female subjects aged 6 to 15 years.
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 subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 6 to 17 years and for female subjects aged 6 to 15 years. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1.
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 subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 6 to 17 years and for female subjects aged 6 to 15 years. Absolute change in percent predicted FEV1 over 24 weeks of ivacaftor treatment (from Week 12 \[Part 1: Treatment Period 2\] through Week 36 \[Part 2\]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2, as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2.
Adverse Event: any untoward medical occurrence in a participant during the study, including any unfavorable and unintended sign, symptom, or disease whether or not it was considered to be study drug related. This included any newly occurring event or previous condition that increased in severity or frequency after obtaining informed consent and assent (where applicable). SAE: medical event or condition, which resulted in any of following, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Non-Serious AEs included all AEs except SAEs.
Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.
Safety of ivacaftor will be determined by number of participants with adverse events (including serious adverse events).
Number of participants with abnormal serum chemistry values compared to screening values will also be used to determine safety of ivacaftor.
Safety of ivacaftor will also be determined by number of participants with abnormal changes in their screening hematology values.
Number of participants with abnormal changes in their screening ECGs is another factor that will be used to evaluate the safety of ivacaftor.
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).
Lung clearance index (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 SF6 concentration to 1/40th of the starting value.
Adverse event data were collected up to the follow-up visit (5 to 9 days after last dose of study drug). Serious adverse events that were ongoing at the follow-up visit were followed until the event resolved, returned to baseline, or was determined to be a stable or chronic condition.
Adverse event data were collected up to the follow-up visit (5 to 9 days after last dose of study drug). Serious adverse events that were ongoing at the follow-up visit were followed until the event resolved, returned to baseline, or was determined to be a stable or chronic condition.
PK Parameters - maximum observed plasma concentrations (Cmax) and area under the concentration versus time curve (AUC),
PK parameters - maximum observed plasma concentrations (Cmax) and area under the concentration versus time curve (AUC),
| Arm | Type | Description |
|---|---|---|
| Ivacaftor | EXPERIMENTAL | There is only one arm to this study. The two sisters with Cystic Fibrosis will both receive Ivacaftor for 6 months for their treatment. |
| Sequence 1: First Ivacaftor (IVA) Then Placebo | EXPERIMENTAL | Participants received IVA 150 milligram (mg) every 12 hours (q12h) for 8 weeks in treatment period 1 followed by placebo matched to IVA for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods. |
| Sequence 2: First Placebo Then IVA | EXPERIMENTAL | Participants received placebo matched to IVA for 8 weeks in treatment period 1 followed by IVA 150 mg q12h for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods. |
| Ivacaftor (Run-in Period) | EXPERIMENTAL | Ivacaftor 150 milligram (mg) tablet orally every 12 hours for 4 weeks. |
| VX-661 + Ivacaftor (Active comparator period) | EXPERIMENTAL | VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks. |
| Ivacaftor monotherapy (Active comparator period) | ACTIVE_COMPARATOR | Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks. |
| Observational Arm | NO_INTERVENTION | - |
| Observational | NO_INTERVENTION | Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet, orally, q12h in the previous Study 110 (NCT01614457) or Study 111 (NCT01614470), were observed (did not receive study drug) in this Study 112 (NCT01707290) for up to 2 years. |
| Placebo | PLACEBO_COMPARATOR | Placebo matched to Ivacaftor tablet orally twice daily for 24 weeks. |
| Part 1: Ivacaftor First, Then Placebo | EXPERIMENTAL | Ivacaftor 150 milligram (mg) tablet orally twice daily for 8 weeks in treatment period 1 followed by placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period. |
| Part 1: Placebo First, Then Ivacaftor | EXPERIMENTAL | Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 1 followed by ivacaftor 150 mg tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period. |
| Part 2: Ivacaftor | EXPERIMENTAL | Ivacaftor 150 mg tablet orally twice daily for 16 weeks. |
| VX-770 | EXPERIMENTAL | VX-770 (ivacaftor) 150 milligram (mg) tablet orally twice daily (q12h). |
| 150 mg Ivacaftor q12h | EXPERIMENTAL | Subjects who received 150 mg of ivacaftor q12h for up to 48 weeks. |
| 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. |
| 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. |
| 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. |
| 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. |
| Treatment Sequence 1 | EXPERIMENTAL | Ivacaftor administered in Treatment Period 1 and placebo administered in Treatment Period 2. |
| Treatment Sequence 2 | EXPERIMENTAL | Placebo administered in Treatment Period 1 and ivacaftor administered in Treatment Sequence 2. |
| Ivacaftor Group A | EXPERIMENTAL | Subjects in Part 1 who first received 25 mg or 75 mg of ivacaftor every 12 hours (q12h) for 14 days, then crossed over to receive the alternate dose for another 14 days. |
| Ivacaftor Group B | EXPERIMENTAL | Subjects in Part 1 who first received 75 mg or 150 mg of ivacaftor q12h for 14 days then crossed over to receive the alternate dose for another 14 days. |
| Ivacaftor Group C | EXPERIMENTAL | Subjects in Part 2 who received 150 mg or 250 mg of ivacaftor q12h for 28 days. |
| Cohort 1 | ACTIVE_COMPARATOR | participants in Cohort 1 will be administered ivacaftor alone followed by ivacaftor with concomitant ciprofloxacin. |
| Cohort 2 | EXPERIMENTAL | Participants in Cohort 2 will be administered VX-661 in combination with ivacaftor followed by VX-661 in combination with ivacaftor and concomitant ciprofloxacin |
| Name | Type | Description |
|---|---|---|
| Ivacaftor | DRUG | Subjects will be treated with ivacaftor for 6 months and followed for 7 months and will undergo assessments along the way to measure sweat chloride and sputum amounts. |
| Placebo | DRUG | Placebo matched to IVA tablet. |
| Tezacaftor/Ivacaftor | DRUG | - |
| Ivacaftor 150 MG | DRUG | Ivacaftor is a CFTR potentiator |
| Placebo-matched-to-ivacaftor tablet | DRUG | Orally every 12 hours up to 4 weeks. |
| Ivacaftor 25 mg/75 mg | DRUG | 25 mg or 75 mg q12h for a total of 28 days (Part 1) |
| Ivacaftor 75 mg/150 mg | DRUG | 75 mg or 150 mg q12h for a total of 28 days (Part 1) |
| Ivacaftor 150 mg or 250 mg | DRUG | 150 mg or 250 mg of ivacaftor q12h for 28 days (Part 2) |
| VX-661 | DRUG | - |
| ciprofloxacin | DRUG | - |
Inclusion Criteria: * Subjects are \>18 years of age and able to provide informed consent. * Subjects reside in the US and are willing to be treated with ivacaftor. * Subjects have the splicing mutation of interest. * Subjects are willing and able to perform requirements of the study. Exclusion Cr...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Vertex Pharmaceuticals Incorporated | VRTX | 8 | PHASE3 | VX-121/TEZ/D-IVA |
| Sionna Therapeutics, Inc. | SION | 2 | PHASE2 | SION-719 |
| BiomX Inc. | PHGE | 1 | PHASE2 | BX004 |
| 4D Molecular Therapeutics, Inc. | FDMT | 1 | PHASE2 | 4D-710 |
| Arcturus Therapeutics Holdings, Inc. | ARCT | 1 | PHASE2 | ARCT-032 |
| Krystal Biotech, Inc. | KRYS | 1 | PHASE1 | KB407 |
| Illumina, Inc. | ILMN | 1 | - | Undisclosed |
Ivacaftor is a small molecule being developed by Vertex Pharmaceuticals for respiratory conditions, specifically Chronic Obstructive Pulmonary Disease and Cystic Fibrosis. It is currently in Phase 2 clinical development as an investigational therapy, meaning it has not yet been approved for these indications.
Ivacaftor is a small molecule therapy targeting the underlying cause of Cystic Fibrosis. While the specific molecular target is not detailed, it is designed to address CFTR function in patients with certain mutations. The drug is being studied in patients with the G551D mutation and those with residual CFTR function.
Ivacaftor is developed by Vertex Pharmaceuticals Incorporated, a biopharmaceutical company traded on the NASDAQ under the ticker symbol VRTX. The company is conducting clinical trials for Ivacaftor in Cystic Fibrosis and Chronic Obstructive Pulmonary Disease.
Ivacaftor is in Phase 2 clinical development. It is an investigational drug and has not been approved by regulatory authorities. The clinical program includes 15 completed trials with a total enrollment of 1,027 participants, all of which have been completed with no active trials currently ongoing.
Ivacaftor has completed several Phase 2 trials including NCT00457821, a safety study in adults with Cystic Fibrosis, and NCT01262352, studying its effect on lung clearance index in patients with the G551D mutation. NCT01685801 examined its effect on lung function in patients with residual CFTR function.
Ivacaftor is being studied in combination with VX-661, another investigational compound. In a Phase 1 trial (NCT02015507), the effect of ciprofloxacin on Ivacaftor and VX-661 in combination with Ivacaftor was examined in healthy volunteers. Ivacaftor itself is the active drug being evaluated.