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Clinical Trial for Age 1 to <2 Years

Safety Evaluated in Patients Aged 1 to 2 Years Who Are Homozygous for the F508del-CFTR Mutation

STUDY DESIGN

Trial 7 | Open-Label Safety Study (Part B)1,2

Trial 7 was a 24-week, open-label study assessing the safety of ORKAMBI in 46 patients aged 1 through 2 years with CF who were homozygous for the F508del-CFTR mutation. Patients received ORKAMBI granules (if 7 to <9 kg: lumacaftor 75 mg/ivacaftor 94 mg; if 9 to <14 kg: lumacaftor 100 mg/ivacaftor 125 mg; if ≥14 kg: lumacaftor 150 mg/ivacaftor 188 mg) mixed with 1 teaspoon (5 mL) of soft food or liquid and administered orally every 12 hours with fat-containing food. All patients continued to take their prescribed CF therapies (including during the 2-week washout period). The primary endpoint was safety and tolerability up to Week 24.

 

Trial 7 | Limitations and Disclosures2

  • 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 bias related to awareness of treatment

Impact of COVID-192

  • Trial 7 was conducted during the COVID-19 pandemic. Vertex implemented safety measures, including at-home safety visits, to provide patients the opportunity to continue the study and minimize risk of COVID-19 exposure through travel
     

 

Download the Clinical Brochure, including information from Trial 7 in patients aged 1 to 2 years.

 

SAFETY PROFILE

The Primary Endpoint Was Safety and Tolerability up to Week 24.
 

The Safety Profile of ORKAMBI in Patients Aged 1 through 2 Years Was Similar to Patients Aged 2 Years and Older1,2 

 

Elevated ALT or AST

ORKAMBI Total, N=46 (%)

>3 x ULN

5 (10.9)

>5 x ULN

2 (4.3)

>8 x ULN

1 (2.2)

  • No patients had total bilirubin levels >2 x ULN
  • No patients experienced treatment interruptions due to transaminase elevations

Discontinuations and Serious AEs

 

  • One patient (2.2%) discontinued treatment with ORKAMBI due to an AE (transaminase elevations)
  • Five patients (10.9%) experienced serious AEs (three with infective pulmonary exacerbations of CF, one with post-procedural fever, and one with DIOS), all of which were considered by study investigators to be mild or moderate in severity

 

  • One patient (2.2%) experienced a respiratory-related AE (dyspnea)
    • It occurred on Day 1 of Trial 7, resulting in treatment interruption. ORKAMBI use resumed as normal on Day 2, and the event did not recur
OTHER RESULTS

Trial 7: Sweat Chloride Results (Pharmacodynamics)

In patients treated with ORKAMBI, sweat chloride reductions were observed as early as Week 41,2

Secondary endpoint: mean absolute change from baseline in sweat chloride concentration
Secondary endpoint: mean absolute change from baseline in sweat chloride concentration

Mean Absolute Change From Baseline in Sweat Chloride

  • From baseline at Week 24 (n=24): -29.1 mmol/L (95% CI: -34.8, -23.4) reduction 
  • After washout, from Week 24 to Week 26 (n=25), increased to +27.3 mmol/L (95% CI: 22.3, 32.3)

There was no direct correlation between decrease in sweat chloride level and improvement in lung function (ppFEV1)1

AE, adverse event; ALT, alanine aminotransaminase; AST, aspartate aminotransaminase; CI, confidence interval; DIOS, distal intestinal obstruction syndrome; ppFEV1, percent predicted forced expiratory volume in 1 second; ULN, upper limit of normal.