SpliSense has commenced a Phase IIb clinical trial of its inhaled antisense oligonucleotide therapy, SPL84, in people with cystic fibrosis (CF).
SPL84 is intended for individuals with CF carrying the 3849+10 kilobase (Kb) C→T mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
The new phase of the SPL84-002 study aims to examine the impact of SPL84 in combination with existing CFTR modulator treatments, building upon results from an earlier Phase IIa segment.
The ongoing placebo-controlled, double-blind, randomised study will recruit around 40 participants who have at least one copy of the mutation and are already on stable treatment with Trikafta, Kaftrio or Alyftrek.
Participants are expected to be randomised in a 4:1 ratio to receive either 50mg of the therapy or placebo by inhalation once a week for 12 weeks.
The main objective of the trial is to assess the safety and tolerability of SPL84.
Secondary objectives include evaluation of lung function, using measures such as ppFEV1 and ppFEF25–75, as well as assessment of respiratory symptoms by cystic fibrosis questionnaire–revised (CFQ-R) respiratory domain scores.
The study also includes exploratory analysis of sputum microbiology and the Lung Clearance Index. SpliSense anticipates top-line results in the second half of 2027.
In a previous Phase IIa segment of the trial, SPL84 was reported to have a favourable safety profile and showed signs of clinical activity.
According to the company, up to 70% of participants who received SPL84 experienced at least a five-point improvement in lung function from baseline.
The current Phase IIb trial will further characterise both the safety and the treatment effect of SPL84 in patients already receiving modulator therapy.
SpliSense CEO Gili Hart said: “Following the favourable safety and efficacy profile demonstrated in the Phase IIa study, we are excited to initiate the Phase IIb study, designed to determine whether once-weekly SPL84 can provide additional clinical benefit for people with the 3849+10kb C→T mutation who are already receiving standard–of–care CFTR modulator therapy.”
SPL84 has received fast track and orphan drug designations from the US Food and Drug Administration, as well as PRIME designation from the European Medicines Agency.
