Clinical Trials for Ages 6 Months to <2 Years
TRIAL 8 (ARRIVAL): Patients with CF age 6 months to less than 2 years. KALYDECO® (ivacaftor) in patients as young as 6 months of age1,2

ON THIS PAGE: Study Design | Safety ProfileSummary of Results

 

STUDY DESIGN1-4

 

  • 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 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*, S1251N, S1255P, S549N, or S549R mutation1-4(mutations in bold were enrolled)
      • 6 to <12 months cohort: Enrolled patients had either a G551D mutation (n=10) or a G178R (n=1) mutation2
      • 12 to <24 months cohort: Enrolled patients had the G551D mutation (n=16), S549N mutation (n=2), or G178R mutation (n=1)3
  • Patients received KALYDECO every 12 hours with fat-containing food, in addition to their prescribed CF therapies, 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 to <25 kg: One 75-mg packet of oral granules2,3

 

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

Secondary endpoints2,3: Absolute change from baseline in sweat chloride concentration at 24 weeks

 

*Patients with the R117H mutation were only eligible to enroll in this study in the US.


 

Trial 8 limitations2,3:

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

SAFETY PROFILE

Discontinuation and serious adverse events2,3

  • 6 to <12 month cohort: There was 1 treatment interruption and no permanent discontinuations due to adverse events. Serious adverse events included viral respiratory tract infection (1), viral rash (1), and cough (1)2
  • 12 to <24 month cohort: 1 patient discontinued due to difficulty with blood draws. 4 serious adverse events occurred in 2 patients3
    • 1 patient had constipation, distal intestinal obstruction syndrome (DIOS), and eczema herpeticum
    • 1 patient had persistent cough

The serious adverse event of constipation was considered possibly related to ivacaftor by the investigator. All other serious adverse events were considered unrelated or unlikely to be related to ivacaftor by the investigator.

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

Transaminase elevations1,2,3,5

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

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

 

Please see Important Safety Information for additional information on liver-related serious adverse events.

 

  • No patients in either cohort had elevations in total bilirubin, or discontinued ivacaftor treatment due to transaminase elevations1
  • 6 to <12 month cohort: During the course of this study, no patient interrupted treatment because of adverse events of elevated liver function tests2
    • On the last day of the study, 1 patient had an LFT elevation that resulted in subsequent treatment interruption2
  • 12 to <24 month cohort: 2 patients had study drug interrupted because of adverse events of elevated liver function tests3
    • 1 patient had adverse events of ALT increased and AST increased that led to study drug interruption5
    • 1 patient had adverse events of ALT increased, AST increased, and GGT increased that led to study drug interruption5
    • Both resumed treatment following a period of study drug interruption with no further elevations3

 

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


SUMMARY OF RESULTS1-3

 

PHARMACODYNAMIC RESULTS1,2
Reduction in sweat chloride from baseline with KALYDECO: Patients age 6 to less than 12 months 

chart

 

bMean (SD) concentrations by visit calculated from the number of children contributing data at each time point.
cCalculated from children with data available at both baseline and Week 24.

  • In the 6 to <12 month 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
  • In clinical studies with KALYDECO, there was no direct correlation between decrease in sweat chloride levels and improvement in lung function (FEV1)1

The safety and efficacy of KALYDECO in patients with CF younger than
6 months of age have not been established. The use of KALYDECO in
children under the age of 6 months is not recommended.1


Reduction in sweat chloride from baseline with KALYDECO: Patients age 12 to less than 24 months1,3

 

chart chart

cCalculated from children with data available at both baseline and Week 24.
dMean (SD) concentrations by visit calculated from the number of children contributing data at each time point.

 

sweat
  • In the 12 month to <24 month cohort (n=10), the mean absolute change from baseline in sweat chloride for patients was −73.5 mmol/L (95% CI: −86.0, −61.0) at Week 24 (secondary endpoint)1,3
     
  • In clinical studies with KALYDECO, there was no direct correlation between decrease in sweat chloride levels and improvement in lung function (FEV1)1

CI, confidence interval; SD, standard deviation.

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