Clinical Trials for Ages 4 Months to <2 Years
TRIAL 8 (ARRIVAL): KALYDECO® (ivacaftor) in patients with CF age 4 months to less than 2 years.1,2

ON THIS PAGE: Study Design | Safety ProfileSummary of Results

STUDY DESIGN

 

  • Trial 8 was a Phase 3, 24-week, open-label, 2-part study of KALYDECO that included the following cohorts of patients with CF: Patients age 4 to <6 months (n=6), patients age 6 to <12 months (n=11) and patients age 12 to <24 months (n=19)1-3
    •  Patients were eligible if they had a G551D, G1244E, G1349D, G178R, G551S, R117H,a S1251N, S1255P, S549N, or S549R mutation2-4
      • 4 to <6 months cohort: Patients had either a G551D mutation (n=5) or a R117H mutation (n=1)2
      • 6 to <12 months cohort: Patients had either a G551D mutation (n=10) or a G178R mutation (n=1)2
      • 12 to <24 months cohort: Patients had either a G551D mutation (n=16), a S549N mutation (n=2), or a G178R mutation (n=1)3
  • Patients in this trial received KALYDECO every 12 hours with fat-containing food, in addition to their prescribed CF therapies. In the 4 to <6 months cohort, patients received 25 mg of KALYDECO oral granules every 12 hours until reaching 6 months of age, after which they could receive 50 mg of KALYDECO oral granules if they weighed 7 kg or more. Patients 6 months and older received KALYDECO every 12 hours based on weight: 5 kg to <7 kg: one 25 mg packet of oral granules, 7 kg to <14 kg: one 50 mg packet of oral granules; ≥14 kg: one 75 mg packet of oral granules1
  • Instruction was provided to administer KALYDECO oral granules mixed with 5 mL of an age-appropriate soft food or liquid, either orally with a syringe or with a spoon, every 12 hours along with a fat-containing food. Bottle use was not recommended5

 

 

Primary endpoint2,3: Safety, assessed by adverse events (AEs) and clinical laboratory assessments

Select secondary endpoint2,3: Absolute change from baseline in sweat chloride concentration at Week 24

 

aPatients with the R117H mutation were only eligible to enroll in this study in the United States.


 

Trial 8 limitations2,3:

  • The study was open label and not placebo controlled; therefore, causality cannot be attributed to KALYDECO
  • All patients in the study knew they were on active drug, which may have introduced bias related to awareness of treatment

SAFETY PROFILE

Discontinuations and serious AEs

  • 4 to <6 months cohort2,6:
    • No treatment discontinuations
    • 1 serious AE included bronchiolitis
  • 6 to <12 months cohort2:
    • There was 1 treatment interruption and no permanent discontinuations due to AEs
    • Serious AEs included viral respiratory tract infection (n=1), viral rash (n=1), and cough (n=1)
  • 12 to <24 months cohort3:
    • 1 patient discontinued due to withdrawal of consent
    • 4 serious AEs occurred in 2 patients3
      • 1 patient had constipation, distal intestinal obstruction syndrome (DIOS), and eczema herpeticum
        • The serious adverse event of constipation was considered possibly related to ivacaftor by the investigator3
      • 1 patient had persistent cough3


All other serious AEs were considered unrelated or unlikely to be related to ivacaftor.2,3

The safety profile of patients in this trial is similar
to that observed in patients age 2 years and older.1

Transaminase elevations1,2

INCIDENCE OF
TRANSAMINASE ELEVATIONS1,2
ELEVATED ALT OR AST 4 TO <6 MONTHS COHORT n/N (%) 6 TO <12 MONTHS COHORT n/N (%) 12 TO <24 MONTHS COHORT n/N (%)
>3x ULN 0/6 (0.0) 1/11 (9.1) 5/18 (27.8)
>5x ULN 0/6 (0.0) 0/11 (0.0) 2/18 (11.1)
>8x ULN 0/6 (0.0) 0/11 (0.0) 2/18 (11.1)

ALT, alanine aminotransferase. AST, aspartate aminotransferase. ULN, upper limit of normal.
 

  • No patients in any cohort had elevations in total bilirubin, or discontinued ivacaftor treatment due to transaminase elevations1
     

Please see Important Safety Information for more information about transaminase elevations reported in patients with CF receiving KALYDECO.


SUMMARY OF RESULTS

 

PHARMACODYNAMIC RESULTS1-3

Reduction in sweat chloride from baseline with KALYDECO in:

 

Patients age 4 to less than 6 months

sweat icon

-50.0 mmol/L
 

  • In the 4 to <6 months cohort (n=3), the mean absolute change from baseline in sweat chloride was -50.0 mmol/L (95% CI: -93.1, -6.9) at Week 24 (secondary endpoint)1

 

Patients age 6 to less than 12 months

sweat

-58.6 mmol/L
 

  • In the 6 to <12 months cohort (n=6), the mean absolute change from baseline in sweat chloride was -58.6 mmol/L (95% CI: -75.9, -41.3) at Week 24 (secondary endpoint)1,2

 

Patients age 12 to less than 24 months

sweat

-73.5 mmol/L
 

  • In the 12 to <24 months cohort (n=10), the mean absolute change from baseline in sweat chloride was −73.5 mmol/L (95% CI: −86.0, −61.0) at Week 24 (secondary endpoint)1,3

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


CI, confidence interval.

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