SpliSense has launched the Phase IIb portion of SPL84-002 to test inhaled antisense therapy SPL84 in CF patients carrying the 3849+10kb C→T CFTR mutation. The double-blind, placebo-controlled study will enrol ~40 participants on stable Trikafta, Kaftrio or Alyftrek and randomise them 4:1 to 50 mg SPL84 or placebo once weekly for 12 weeks. Primary focus is safety and tolerability; secondary measures include ppFEV1, ppFEF25–75 and CFQ-R respiratory scores. Top-line data are expected in H2 2027.
SpliSense Launches Phase IIb Trial of Inhaled SPL84 for Cystic Fibrosis Patients With 3849+10kb C→T Mutation
The ongoing study will recruit around 40 participants. Credit: Gorodenkoff / Shutterstock.com.
SpliSense has initiated the Phase IIb portion of its SPL84-002 study to evaluate inhaled SPL84, an antisense oligonucleotide therapy, in people with cystic fibrosis (CF) who carry the 3849+10kb C→T mutation in the CFTR gene.
Study Design and Population
The randomised, double-blind, placebo-controlled Phase IIb trial plans to enrol about 40 participants who have at least one copy of the 3849+10kb C→T mutation and are on stable treatment with an approved CFTR modulator (Trikafta, Kaftrio or Alyftrek). Subjects are expected to be randomised 4:1 to receive either 50 mg of SPL84 or placebo, delivered by inhalation once weekly for 12 weeks.
Objectives and Endpoints
The trial's primary objective is to assess the safety and tolerability of once-weekly inhaled SPL84 in patients already receiving standard-of-care modulators. Secondary endpoints will evaluate lung function (percent-predicted FEV1 (ppFEV1) and percent-predicted FEF25–75 (ppFEF25–75)) and respiratory symptoms measured by the Cystic Fibrosis Questionnaire–Revised (CFQ-R) respiratory domain. Exploratory analyses include sputum microbiology and Lung Clearance Index measurements.
Background and Rationale
SpliSense is running this Phase IIb segment to determine whether SPL84 provides additional clinical benefit on top of existing modulator therapy. In the earlier Phase IIa segment, SPL84 exhibited a favourable safety profile and preliminary signs of clinical activity: according to the company, up to 70% of treated participants experienced at least a five-point improvement in lung function versus baseline.
“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,” said SpliSense CEO Gili Hart.
Regulatory Status and Timeline
SPL84 has received Fast Track and Orphan Drug designations from the US Food and Drug Administration and PRIME designation from the European Medicines Agency. SpliSense expects to report top-line results in the second half of 2027.
The Phase IIb segment will further characterise safety and the magnitude of any treatment effect of SPL84 when added to current modulator regimens, informing potential next steps in development.
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