TRIAL 2: A double-blind, active-controlled, head-to-head Phase 3 trial in patients homozygous for F508del mutation1,2

Study Design

WEEK -4

BASELINE
RANDOMIZED 1:1

WEEK 24a

Run-in with tezacaftor/ivacaftor and ivacaftor 100 mg/150 mg qd and 150 mg qd with fat-containing food

TRIKAFTA®

(elexacaftor/tezacaftor/
ivacaftor and ivacaftor) 200 mg/100 mg/150 mg qam and 150 mg qpm with fat-containing food (N=55)

 

Active Comparator

(tezacaftor/ivacaftor and ivacaftor) 100 mg/150 mg qam and 150 mg qpm with fat-containing food (N=52)

Prior to the run-in period, all patients in this study discontinued previous CFTR modulator therapies but remained on their standard-of-care CF therapies.1

aAll patients who completed the study were eligible to roll over into a 96-week, open-label extension study.1 

Key inclusion criteria1,2b 

  • Confirmed CF diagnosis, clinically stable, and at least 12 years of age
  • Homozygous for the F508del mutation
  • ppFEV1 between 40% and 90% at screening

bKey exclusion criteria included clinically significant cirrhosis with or without portal hypertension, a history of colonization with organisms associated with a more rapid decline in pulmonary status (including, but not limited to, Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus), and solid organ or hematologic transplantation.1,3 

PRIMARY ENDPOINT1
  • Absolute change in ppFEV1 from baseline at Week 4
KEY SECONDARY ENDPOINTS1c

FROM BASELINE AT WEEK 4:

  • Absolute change in sweat chloride
  • Absolute change in CFQ-R Respiratory Domain score

cA hierarchical testing procedure was performed for key secondary endpoints. For an endpoint to be significant, both it and all previous tests in the hierarchy had to achieve P<0.05.2 

Baseline characteristics in Trial 24
TRIKAFTA
Tezacaftor/ivacaftor and ivacaftor
Sex, female, %
56.4
53.8
Mean age, years (range)
28.8 (12.7-54.1)
27.9 (12.4-60.5)
Mean BMI, kg/m2 (range)
21.8 (16.0-28.4)
21.9 (15.6-34.6)
Mean ppFEV1 (range)
61.6 (35.0-87.4)
60.2 (35.0-89.0)
Mean SwCI, mmol/L (range)
91.4 (67.0-114.0)
90 (60.5-112.0)
Back to Top

Summary of Efficacy Results

Significant improvements in lung function and sweat chloride vs active comparator1,2

PRIMARY ENDPOINT

Absolute Change in ppFEV1 from Baselined

Increase

10.0

Percentage
Points

IMPROVEMENT vs tezacaftor/ivacaftor and ivacaftor at Week 4 (95% CI: 7.4, 12.6; P<0.0001)

All patients began treatment with tezacaftor/ivacaftor and ivacaftor for 4 weeks

Expand

SECONDARY ENDPOINT1

-45.1

mmol/L

SIGNIFICANT REDUCTION IN SWEAT CHLORIDE
Compared with tezacaftor/ivacaftor and ivacaftor at Week 4 (95% CI: -50.1, -40.1; P<0.0001)

Sweat chloride levels may not correlate with improvements in lung function (ppFEV1).

Back to Top

Significantly improved CFQ-R Respiratory Domain score vs active comparator1,2

SECONDARY ENDPOINT

Mean Absolute Change from Baseline in CFQ-R Respiratory Domain Score

Increase

17.4

POINTS IMPROVEMENT

The MCID threshold for CFQ-R Respiratory Domain score is 4 points in patients with CF with stable respiratory symptoms and represents the minimal change a patient can detect.5 

CFQ-R Respiratory Domain score measured composite patient-reported outcomes in the following respiratory symptoms6: 

  • Waking up from coughing
  • Wheezing
  • Coughing
  • Congestion
  • Difficulty breathing
  • Mucus production

Expand

Back to Top

BMI, body mass index; CF, cystic fibrosis; CFTR, cystic fibrosis transmembrane conductance regulator; CFQ-R, Cystic Fibrosis Questionnaire-Revised; CI, confidence interval; IV, intravenous; LS, least square; MCID, minimal clinically important difference; ppFEV₁, percent predicted forced expiratory volume in 1 second; q12h, every 12 hours; qam, every morning; qpm, every evening; RR, rate ratio, SE, standard error; SwCl, sweat chloride; WK, week.