Vertex posts Phase 3 ELX/TEZ/IVA study results in infants with cystic fibrosis

Vertex Pharmaceuticals Incorporated posted results for a Phase 3 study of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) in cystic fibrosis participants 12 to less than 24 months of age. The study record, NCT05882357, lists results first posted on 2026-10-15. The study is marked completed, and primary completion is listed as 2025-09-04.

The study record

The official title describes a Phase 3, open-label study evaluating the pharmacokinetics, safety, and tolerability of ELX/TEZ/IVA. The record lists the allocation as non-randomized and the intervention model as sequential. The study began on 2023-06-27. The record lists 67 unique participants across two parts. Three participants who completed Part A continued into Part B, so they appear in both parts.

Participants carried at least 1 F508del mutation in the CFTR gene or another ELX/TEZ/IVA-responsive CFTR mutation. The record lists sites in Australia, Canada, Denmark, Germany, the Netherlands, Switzerland and the United Kingdom. All baseline participants in both parts are listed as 18 years or younger.

Part A and Part B

Part A enrolled and dosed 15 participants. Participants received ELX 40 milligram (mg), TEZ 20 mg and IVA 30 mg fixed-dose combination granules each morning, plus 25 mg IVA each evening, for 15 Days. All 15 completed Part A.

Part B enrolled 55 participants, and 54 received at least one dose. The record lists three dosing regimens based on body weight at Day 1.

Dosage 1: ELX 80 mg, TEZ 40 mg and IVA 60 mg each morning, and 59.5 IVA mg each evening.
Dosage 2: ELX 60 mg, TEZ 30 mg and IVA 45 mg each morning, and 50 mg IVA each evening.
Dosage 3: ELX 40 mg, TEZ 20 mg and IVA 30 mg each morning, and 25 mg IVA each evening.

In Part B, 53 participants completed the study. The record lists 1 participant who prematurely discontinued and 1 participant never dosed. The record says Dosage 3 data are not available for the pharmacokinetic outcome because participants weighing less than 7 kg were not enrolled.

The primary outcomes

The record lists three primary outcomes: pre-dose concentration (Ctrough) of ELX, TEZ, IVA and their metabolites in Part A, and safety and tolerability measured by treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) in Part A and in Part B.

In Part A, the median Ctrough at Day 15 was 0.907 microgram per milliliter for ELX (standard deviation 0.447), 0.691 for TEZ (0.245) and 0.151 for IVA (0.0669). The record lists 15 participants for this measure.

The safety data list 14 of 15 participants in Part A had TEAEs and none had SAEs. In Part B, 53 of 54 participants had TEAEs and 6 had SAEs. The record lists no deaths in either part.

The secondary outcomes

Treatment in Part B was followed by pre-dose concentration measures at Day 15 and at Week 4, 12 and 16. The Dosage 1 mean ELX concentration at Week 16 was 2.45 microgram per milliliter (standard deviation 1.34), measured in 40 participants.

The record also posts the absolute change in sweat chloride (SwCl) from baseline through Week 24 for Part B. The least squares mean change was -71.8 millimole per liter (mmol/L), with a 95 percent confidence interval of -75.4 to -68.2. The record lists 48 participants analyzed.

Adverse events

The record lists other adverse events above the posted frequency threshold of 5. In Part B, of 54 participants, pyrexia affected 21, nasopharyngitis 14, vomiting 13, and infective pulmonary exacerbation of cystic fibrosis 12. Diarrhoea affected 8 participants and constipation 7. In Part A, constipation and diarrhoea each affected 4 of 15 participants. The record also lists an anaphylactic reaction in 1 of 15 Part A participants.

The record and next steps

The record does not state what the sponsor plans next. The record describes Vertex data sharing as a process set out on the sponsor site, and it lists individual participant data sharing as NO.