Clinical Trials for 12 Years or Older

12+ Years (Trial 1)

12+ Years (Trial 7)

Components

TRIAL 1 (STRIVE): Patients with CF age 12 years and older with a G551D mutation. KALYDECO® (ivacaftor) achieved significant improvements across multiple clinical endpoints in patients with a G551D mutation1-3

Mutation Eligible for Study1 (mutation in bold was enrolled)
G551D

 

STUDY DESIGN1

  • Trial 1 was a 48-week, Phase 3, randomized, double-blind, placebo-controlled trial (N=161) in patients with CF age 12 years and older (mean age: 26 years) and a G551D mutation 
  • Patients had to have FEV1 40%-90% predicted at screening [mean FEV1 64% predicted at baseline (range: 32%-98%)]  
  • Patients received KALYDECO 150 mg or placebo every 12 hours with fat-containing food, in addition to their prescribed CF therapies. Use of hypertonic saline was not permitted 

Primary endpoint1: Improvement in lung function as determined by the mean absolute change from baseline in ppFEV1 through 24 weeks

Other efficacy endpoints1: Absolute change in ppFEV1 through Week 48, improvement from baseline in CFQ-R Respiratory Domain score through Weeks 24 and 48, time to first pulmonary exacerbation through Weeks 24 and 48, absolute change from baseline in body weight at Weeks 24 and 48, and absolute change from baseline in sweat chloride concentration through Weeks 24 and 48
 


SUMMARY OF RESULTS1,3,4

Significant improvements in lung function were seen through 24 weeks and persisted through 48 weeks1,3,4

lungs

Treatment difference through:

First Column

24 weeks (primary endpoint)
+10.6 points
(95% CI: 8.6, 12.6; P<.0001)
 

Second Column

48 weeks (other endpoint)a 
+10.5 points
(95% CI: 8.5, 12.5; P<.0001)


chart

aTreatment difference = effect of KALYDECO – effect of placebo.1

Primary endpoint was assessed through 24 weeks for Trial 1 and was based on a mixed-effects model for repeated measures (MMRM).1,3


Clinical endpoints studied in Trial 1 for KALYDECO showed significant, sustained improvements vs placebo1

Score

CFQ-R RESPIRATORY DOMAIN SCORE 
Treatment difference through:

First Column

24 weeksa
+8.1 points
(95% CI: 4.7, 11.4; P<.0001)

Second Column

48 weeksa
+8.6 points
(95% CI: 5.3, 11.9; P<.0001)
 

exacerbations

RELATIVE RISK OF PULMONARY EXACERBATION 
Treatment difference through:

First Column

24 weeksa 
60% reduction
(HR, 0.40; P=.0016)

Second Column

48 weeksa
54% reduction
(HR, 0.46; P=.0012)

  • Pulmonary exacerbation was defined as a change in antibiotic therapy (IV, inhaled, or oral) as a result of 4 or more of 12 pre-specified sino-pulmonary signs/symptoms1
scale

BODY WEIGHT 
Treatment difference at:

First Column

24 weeksa 
+2.8 kg
(95% CI: 1.8, 3.7; P<.0001)

Second Column

48 weeksa
+2.7 kg
(95% CI: 1.3, 4.1; P=.0001)

  • Changes in BMI normalized for age and sex in patients <20 years of age were consistent with absolute change from baseline in weight1
sweat

SWEAT CHLORIDE 
Treatment difference through:

First Column

24 weeksa
−48 mmol/L
(95% CI: -51, -45; P<.0001)

Second Column

48 weeksa
−48 mmol/L
(95% CI: -51, -45; P<.0001)

  • There was no direct correlation between decrease in sweat chloride levels and improvement in lung function (FEV1)1

aTreatment difference = effect of KALYDECO – effect of placebo.1 

HR, hazard ratio; IV, intravenous; BMI, body mass index.

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Components

TRIAL 7: Patients with CF age 12 years and older with specific ivacaftor-responsive mutations. KALYDECO® (ivacaftor) improved lung function vs placebo overall and across all pre-specified subgroups1

Mutations Eligible for Study1,2 (mutations in bold were enrolled)

  • Patients were heterozygous for the F508del mutation and a second mutation predicted to be responsive to ivacaftor 
  • The 5 splice mutations studied were: 2789+5G→A, 3272-26AG, 3849+10kbCT, 711+3A→G, E831X (n=94 for KALYDECO and n=97 for placebo)
  • The 11 missense mutations studied were: A455E, D1152H, D579G, L206W, P67L, R1070W, R117C, R347H, R352Q, S945L, S977F (n=62 for KALYDECO and n=63 for placebo)
  • D110E, D110H, D1270N, E56K, E193K, F1052V, F1074L, K1060T, R74W 

STUDY DESIGN1,3

CFTR-targeted therapy expanded to patients with responsive splice and missense mutations1 

 

  • Trial 7 was an 8-week, randomized, double-blind, placebo-controlled, 2-period, crossover design trial (N=246) in patients with CF age 12 years and older (mean age: 35 years)
  • Patients had to have FEV1 40%-90% predicted at screening [mean FEV1 62% predicted at baseline (range: 35%-94%)] 
  • Patients received KALYDECO 150 mg or placebo every 12 hours with fat-containing food, in addition to their prescribed CF therapies 

Primary endpoint1: Mean absolute change from baseline in ppFEV1 to the average of Weeks 4 and 8

Key secondary endpoint1: Absolute change from baseline in CFQ-R Respiratory Domain score averaged at Weeks 4 and 8 
 


SUMMARY OF RESULTS1,3


Significant improvement in ppFEV1 by Day 15 maintained through 8 weeks1,3
 

chart

 

Adapted with permission from Rowe SM et al. N Engl J Med. 2017;377(21);2024-2035.
aThe complete study design and results are not reported here; only the KALYDECO and placebo groups are shown


 

Improvements in ppFEV1 were observed with KALYDECO across all pre-specified subgroups vs placebo3,b,c

 

subgroup

 

bAdditional subgroups analyzed included: region; sex; colonization of Pseudomonas aeruginosa; use of azithromycin; and use of inhaled antibiotics, bronchodilators, hypertonic saline, and corticosteroids.3

cTreatment difference = effect of KALYDECO – effect of placebo.1

  • For individual mutations, changes in ppFEV1 varied by genotype and ranged from +2.4% points to +13.3% points; see the full Prescribing Information for results by mutation. These were ad hoc analyses1

Significant improvement in CFQ-R Respiratory Domain score from baseline for KALYDECO vs placebo overall1,3

 

  • The overall treatment difference was 9.7 points (95% CI: 7.2, 12.2; P<.0001)
  • For individual mutations, results varied by genotype and ranged from -8.3 to 44.4; see full Prescribing Information for results by mutation. These were ad hoc analyses
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