Table 2.
Chronology of the randomized, double-blind, placebo-controlled Orkambi phase 2 and 3 studies in patients bearing a F508del-mutation of the CFTR
| Type | Name | Objectives | Treatment | Patient Collective | Duration | Endpoints |
|---|---|---|---|---|---|---|
| Phase 2A | 101 | Safety and tolerability of LUMA | LUMA 25, 50, 100, 200 mg qd; orally | 89 patients with a homozygous F508del-CFTR mutation | 28 d |
Primary endpoints: • Change of CFTR function measured by sweat chloride concentration • Safety Secondary endpoints: • Absolute change in predicted FEV1 percentage • Change in sweat chloride concentration from baseline • Change in CFQ-R score |
| Phase 2 | 102 | Safety and tolerability of LUMA-IVA combination | • Cohort 1: LUMA 200 mg qd followed by LUMA 200 mg qd/ IVA 150 or 250 mg q12h • Cohort 2: LUMA 200, 400, 600 mg qd followed by LUMA/IVA 250 mg q12h • Cohort 3: LUMA 400 mg q12h followed by LUMA 400 mg q12h/ IVA 250 mg q12h • Cohort 4: LUMA 400 mg q/12h followed by LUMA 400 mg qd/ IVA 250 mg q12h |
312 patients with homozygous (cohort 1 &3) or heterozygous (cohort 4) F508del-CFTR mutation (cohort 2 mixed) | • Cohort 1: 14 d mono- followed by 7 d combination therapy • Cohort 2 & 3: 28 d mono-followed by 28 d combination therapy • Cohort 4: 56 d of combination therapy |
|
| TRAFFIC and TRANSPORT studies | ||||||
| Phase 3 | 103 | Efficacy and safety of LUMA-IVA combination | LUMA 600 or 400 mg qd/ IVA 250 mg q12h | 549 patients with a homozygous F508del-CFTR mutation | Up to 24 w + 5 d |
Primary endpoints: • Absolute change from baseline in predicted FEV1 percentage at week 24 Secondary endpoints: • Relative change from baseline in predicted FEV1 percentage (for week 16 & 24) • Absolute change from baseline in BMI percentage at week 24 • Absolute change from baseline in CFQ-R score at week 24 • Percentage of patients with a relative increase from baseline of ≥5% in the percentage predicted FEV1 • Number of pulmonary exacerbations through week 24 • Safety |
| Phase 3 | 104 | Efficacy and safety of LUMA-IVA combination | LUMA 600 or 400 mg qd/ IVA 250 mg q12h | 559 patients with a homozygous F508del-CFTR mutation | Up to 24 w + 5 d | |
| Phase 3 | 105 | Long term efficacy and safety of LUMA-IVA combination | • Part A: LUMA 600 or 400 mg qd/ IVA 250 mg q12h • Part B: LUMA 400 mg qd/IVA 250 mg q12h |
• Part A: 1031 patients with a homozygous F508del-CFTR mutation (including patients from study 103/104 • Part B: 119 patients with a heterozygous F508del-CFTR mutation |
~96 w | |