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Patients with CF shown throughout may or may not currently be on TRIKAFTA.

TRIAL 2: A double-blind, active-controlled, head-to-head Phase 3 trial in patients homozygous for F508del mutation^1,2

On this Page: Study Design | Summary of Efficacy Results

Study Design

WEEK -4

BASELINE
RANDOMIZED 1:1

WEEK 24^a

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

TRIKAFTA^TM

(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 criteria^1,2b

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 ENDPOINTS^1c

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)

Summary of Efficacy Results

Significant improvements in lung function and sweat chloride vs active comparator^1,2

PRIMARY ENDPOINT

Absolute Change in ppFEV₁ from Baseline^d

10.0

Percentage
Points

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

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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).

Significantly improved CFQ-R Respiratory Domain score vs active comparator^1,2

SECONDARY ENDPOINT

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

17.4

POINTS IMPROVEMENT
vs tezacaftor/ivacaftor and ivacaftor at Week 4 (95% CI: 11.8, 23.0; P<0.0001)

vs tezacaftor/ivacaftor and ivacaftor at Week 4 (95% CI: 11.8, 23.0; P<0.0001)

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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.

See the Trial 1 results>

See the safety profile of TRIKAFTA>

Indications and Usage

TRIKAFTA is indicated for the treatment of CF in patients aged 12 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one F508del mutation.

Important Safety Information

Liver Function Test Elevations

Elevated transaminases have been observed in patients with CF treated with TRIKAFTA. Bilirubin elevations have also been observed with TRIKAFTA treatment. Assessments of liver function tests (ALT, AST, and bilirubin) are recommended prior to initiating TRIKAFTA, every 3 months during the first year of treatment, and annually thereafter. For patients with a history of hepatobiliary disease or liver function test elevations, more frequent monitoring should be considered

In the event of significant elevations in liver function tests e.g. ALT or AST >5x the upper limit of normal (ULN) or ALT or AST >3x ULN with bilirubin >2x ULN, dosing should be interrupted and laboratory tests closely followed until the abnormalities resolve. Following the resolution of liver function test elevations, consider the benefits and risks of resuming treatment

Concomitant Use With CYP3A Inducers

Exposure to ivacaftor is significantly decreased and exposure to elexacaftor and tezacaftor are expected to decrease by the concomitant use of strong CYP3A inducers, which may reduce the therapeutic effectiveness of TRIKAFTA. Co‑administration with strong CYP3A inducers is not recommended

Concomitant Use With CYP3A Inhibitors

Exposure to elexacaftor, tezacaftor, and ivacaftor are increased when co-administered with strong or moderate CYP3A inhibitors. The dose of TRIKAFTA should be reduced when used concomitantly with moderate or strong CYP3A inhibitors

Cataracts

Cases of non-congenital lens opacities have been reported in pediatric patients treated with ivacaftor-containing regimens. Baseline and follow up ophthalmological examinations are recommended in pediatric patients initiating treatment with TRIKAFTA

Pediatric Use

The safety and effectiveness efficacy of TRIKAFTA in patients with CF younger than 12 years of age have not been established

Serious Adverse Reactions

Serious adverse reactions that occurred more frequently in patients treated with TRIKAFTA compared to placebo were rash (1% vs <1%) and influenza (1% vs 0). There were no deaths in Trials 1 and 2

Most Common Adverse Reactions

The most common adverse reactions occurring in ≥8% of patients treated with TRIKAFTA (N=202) and at a frequency higher than for placebo (N=201) by ≥1% in the 24 week placebo-controlled, parallel-group Phase 3 trial (Trial 1) were headache, diarrhea, upper respiratory tract infection, abdominal pain, alanine aminotransferase increased, nasal congestion, blood creatine phosphokinase increased, aspartate aminotransferase increased, rash, and rhinorrhea
The safety profile for the patients receiving TRIKAFTA (N=55) in the 4-week, randomized, double-blind, active-controlled Phase 3 trial (Trial 2) was similar to that observed in Trial 1

Click here to access full Prescribing Information for TRIKAFTA.

Indications and Usage

TRIKAFTA is indicated for the treatment of CF in patients aged 12 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one F508del mutation.

Important Safety Information

Liver Function Test Elevations

In the event of significant elevations in liver function tests e.g. ALT or AST >5x the upper limit of normal (ULN) or ALT or AST >3x ULN with bilirubin >2x ULN, dosing should be interrupted and laboratory tests closely followed until the abnormalities resolve. Following the resolution of liver function test elevations, consider the benefits and risks of resuming treatment

Concomitant Use With CYP3A Inducers

Exposure to ivacaftor is significantly decreased and exposure to elexacaftor and tezacaftor are expected to decrease by the concomitant use of strong CYP3A inducers, which may reduce the therapeutic effectiveness of TRIKAFTA. Co‑administration with strong CYP3A inducers is not recommended

Concomitant Use With CYP3A Inhibitors

Exposure to elexacaftor, tezacaftor, and ivacaftor are increased when co-administered with strong or moderate CYP3A inhibitors. The dose of TRIKAFTA should be reduced when used concomitantly with moderate or strong CYP3A inhibitors

Cataracts

Cases of non-congenital lens opacities have been reported in pediatric patients treated with ivacaftor-containing regimens. Baseline and follow up ophthalmological examinations are recommended in pediatric patients initiating treatment with TRIKAFTA

Pediatric Use

The safety and effectiveness efficacy of TRIKAFTA in patients with CF younger than 12 years of age have not been established

Serious Adverse Reactions

Serious adverse reactions that occurred more frequently in patients treated with TRIKAFTA compared to placebo were rash (1% vs <1%) and influenza (1% vs 0). There were no deaths in Trials 1 and 2

Most Common Adverse Reactions

The most common adverse reactions occurring in ≥8% of patients treated with TRIKAFTA (N=202) and at a frequency higher than for placebo (N=201) by ≥1% in the 24 week placebo-controlled, parallel-group Phase 3 trial (Trial 1) were headache, diarrhea, upper respiratory tract infection, abdominal pain, alanine aminotransferase increased, nasal congestion, blood creatine phosphokinase increased, aspartate aminotransferase increased, rash, and rhinorrhea
The safety profile for the patients receiving TRIKAFTA (N=55) in the 4-week, randomized, double-blind, active-controlled Phase 3 trial (Trial 2) was similar to that observed in Trial 1

Click here to access full Prescribing Information for TRIKAFTA.

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

Summary of Efficacy Results

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

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

Indications and Usage

Important Safety Information

Liver Function Test Elevations

Liver Function Test Elevations

Indications and Usage

Important Safety Information

Liver Function Test Elevations

Liver Function Test Elevations

TRIAL 2: A double-blind, active-controlled, head-to-head Phase 3 trial in patients homozygous for F508del mutation^1,2

Significant improvements in lung function and sweat chloride vs active comparator^1,2

Significantly improved CFQ-R Respiratory Domain score vs active comparator^1,2