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IVA

Phase 3

Cystic Fibrosis | Small molecule | Respiratory |Vertex Pharmaceuticals Incorporated|Last Updated: Oct 23, 2024

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMCBiomarker
Total Trials3
Total Enrollment368
FDA Designations
No designations recorded
Clinical Trials (3)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT03277196A Study to Evaluate the Safety of Long-term Ivacaftor Treatment in Participants With Cystic Fibrosis Who Are Less Than 24 Months of Age at Treatment Initiation and Have an Approved Ivacaftor-Responsive MutationPHASE3 COMPLETED 86Aug 16, 2017Oct 2, 2023Oct 23, 202429 United States, Australia +4
NCT02725567A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who Are Less Than 24 Months of Age and Have an Ivacaftor-Responsive CFTR MutationPHASE3 COMPLETED 57Jun 2, 2016Jun 28, 2022Sep 7, 202323 United States, Australia +3
NCT03227471A Study of VX-445 in Healthy Subjects and Subjects With Cystic FibrosisPHASE1 COMPLETED 225Jan 23, 2017Mar 27, 2018Jan 18, 202238 United States, Australia +2
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Study Endpoints
Primary Endpoints
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Day 1 up to Week 120
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)
Day 1 through Day 70
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Pre-dose, 2-4 hours, 6-8 hours, 24-60 hours post-dose
Part B +A/B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)
Day 1 through Week 38
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Day 4 (pre-dose, 2-4 hours, 6-8 hours post-dose); Day 15 (pre-dose); Week 4 (pre-dose); Week 8 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 12 (pre-dose); Week 18 (pre-dose) and Week 24 (pre-dose)
Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
From first dose of study drug in treatment period up to safety follow-up (up to 28 days)
Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
From first dose of study drug in TC treatment period up to 28 days after last dose of study drug (up to 5 weeks)
Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
From Baseline through Day 29

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Part E: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
From Baseline through Day 29

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Part F: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
From Baseline through Day 29

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Secondary Endpoints
Absolute Change in Sweat Chloride
From Baseline at Week 96
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Week 2 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 8 (pre-dose,1 hour, 4-hour post-dose); Week 24 (pre-dose, 2-4 hours post dose)
Part B + A/B: Absolute Change From Baseline in Sweat Chloride
From Baseline at Week 24
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Ivacaftor ArmEXPERIMENTALParticipants less than (\<) 24 months of age and weighing 5 to less than (\<) 7 kilogram (kg) received 25 mg IVA every 12 hours (q12h), 7 to \<14 kg received 50 mg IVA q12h, and those weighing 14 to \<25 kg received 75 mg IVA q12h. Participants more than or equal (\>=) 24 months of age and weighing \<14 kg received 50 mg IVA q12h, and those weighing more than or equal to (\>=)14 kg received 75 mg IVA q12h in the treatment period for up to 96 weeks. Doses were determined based on safety and pharmacokinetic (PK) data from parent study, age and weight.
Observational ArmNO_INTERVENTION -
Part A: 3 to <24 monthsEXPERIMENTALParticipants weighing 5 to less than (\<) 7 kilogram (kg) received 25 milligram (mg) IVA, 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA administered every 12 hours (q12h) on Days 1 through 3 and 1 morning dose on Day 4.
Part B + A/B:1 to < 24 monthsEXPERIMENTALParticipants 4 to \<6 months of age and weighing greater than or equal to (≥) 5 kg received 25 mg IVA q12h. At 6 months of age and older, participants weighing 5 to \<7 kg received 25 mg IVA, 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA q12h for 24 weeks on Part B. For Part A/B, participants 1 to \<4 months weighing 3 kg to \<5 kg received an initial low dose of 5.7 mg q12h IVA and those weighing ≥5 kg received 11.4 mg q12h IVA for the first 15 days of IVA treatment. Doses were maintained or adjusted upward at Day 15 and based on weight and/or age once they reached 4 months of age.
Part A: Pooled Placebo (Except Cohort A7)PLACEBO_COMPARATORParticipants without CF who received single dose of placebo matched to VX-445 in Cohort A1 to A5.
Part A: VX-445 (Except Cohort A7)EXPERIMENTALParticipants without CF who received single ascending dose of VX-445 tablet starting from 20 milligrams (mg) to 360 mg in Cohort A1 to A5.
Part A: VX-445 (Cohort A7)EXPERIMENTALParticipants without CF who received single dose of VX-445 100 mg tablet on Day 1 in fasted state and on Day 7 in fed state, followed by VX-445 20 mg intravenous (IV) injection on Day 13 in fed state in Cohort A7.
Part B: Pooled Placebo (Cohort B1 to B4)PLACEBO_COMPARATORParticipants without CF who received multiple doses of placebo matched to VX-445 once daily (qd) for 10 days in Cohort B1 to B4.
Part B: VX-445 (Cohort B1 to B4)EXPERIMENTALParticipants without CF who received VX-445 tablet qd for 10 days in Cohort B1 (60 mg), B2 (120 mg), B3 (240 mg) and B4 (340 mg).
Part C: Pooled Placebo (Cohort C1 to C3)PLACEBO_COMPARATORParticipants without CF who received placebo matched to VX-445/TEZ/IVA triple combination (TC) qd in the morning and placebo matched to IVA in the evening for 14 days.
Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3)EXPERIMENTALParticipants without CF who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C1; VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C2 and VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C3 for 14 days.
Part D: PlaceboPLACEBO_COMPARATORParticipants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC qd in the morning and placebo matched to IVA qd in the evening for 4 weeks in the TC treatment period.
Part D: VX-445/TEZ/IVA TC - Low DoseEXPERIMENTALParticipants with CF, F/MF genotype who received VX-445 50 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
Part D: VX-445/TEZ/IVA TC - Medium DoseEXPERIMENTALParticipants with CF, F/MF genotype who received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
Part D: VX-445/TEZ/IVA TC - High DoseEXPERIMENTALParticipants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
Part E: TEZ/IVAACTIVE_COMPARATORFollowing run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.
Part E: VX-445/TEZ/IVA TCEXPERIMENTALFollowing run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd /IVA 150 mg q12h for 4 weeks in the TC treatment period.
Part F: PlaceboPLACEBO_COMPARATORParticipants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.
Part F: VX-445/TEZ/VX-561 TCEXPERIMENTALParticipants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
Interventions
NameTypeDescription
IVADRUGGranules for oral administration.
TEZ/IVADRUGTEZ/IVA fixed-dose combination for oral administration.
VX-445DRUGVX-445 tablet for oral administration.
Matched PlaceboDRUGMatched placebo.
TEZDRUGTablet for oral administration.
VX-561DRUGTablet for oral administration.
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Eligibility Criteria
Age Range0 Months — 24 Months
SexALL
Healthy VolunteersNo
Study Sites29

Inclusion Criteria: Ivacaftor Arm: Participants From Study 124 (NCT02725567 ) Part B: * Participants transitioning from Study 124 Part B must have completed the last study visit of Study 124 Part B. * As judged by the investigator, parent or legal guardian must be able to understand protocol requi...

Countries:United StatesAustraliaCanadaGermanyIrelandUnited KingdomBelgiumNetherlands
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