A76-28 Safety and Bronchoscopy Evaluation of an Inhaled mRNA Treatment for Primary Ciliary Dyskinesia Due to Disease Causing DNA Variants in the DNAI1 Gene: Phase 1a Single-dose and Phase 1b Multiple-dose Open-label Trials
M R Loebinger, M Bottier, P L Shah, T Burgoyne, E Howieson, D Morris-Rosendahl, R Hjeij, N T Loges, J Couch, J G Matthews, V Daryani, S Bradley, P Ryali, V Kharitonov, D Brimhall, L Morgan, H Omran, A Shoemark, C Hogg,Abstract
Background
Primary ciliary dyskinesia (PCD) is a rare disease characterized by ciliary dysfunction, resulting in defective mucociliary clearance. There is an unmet need for PCD treatments targeting these underlying ciliary defects. We report the first-in-human results from two clinical trials using RCT1100, an inhaled mRNA encapsulated in a novel lipid nanoparticle formulation, developed for the treatment of patients with PCD caused by dynein axonemal intermediate chain 1 (DNAI1) gene variants.
Methods
RCT1100-101 was a Phase 1a, open-label, sequential cohort design trial conducted at 3 sites (UK, USA, Australia). Adult participants received a single RCT1100 dose (3 or 5 mg). RCT1100-102 was a Phase 1b, open-label, multiple-dose trial conducted at 1 site (UK). Participants were treated with 3 or 5 mg RCT1100 three times a week for 12 weeks, with a 12-week follow-up period. The primary outcomes in both trials were safety and tolerability; participants administered at least one RCT1100 dose were included in the safety analysis. RCT1100-102 included secondary outcomes of ciliary structure and function conducted on pre- and post-treatment bronchial samples.
Findings
Between 19 December 2023 and 13 January 2025, 9 adult participants (6 [66·7%] male, 3 (33·3%] female) were enrolled in RCT1100-101. Between 20 September 2024 and 27 August 2025, 7 participants (4 [57·1%] male, 3 [42·9%] female) were enrolled in RCT1100-102. Treatment-emergent adverse events (TEAEs) and treatment-related TEAEs were reported in 8 participants (88·9%) in RCT1100-101 and 7 participants (100%) in RCT1100-102. No TEAEs of Grade ≥3 or serious adverse events were reported. No difference was seen in the average number of outer dynein arms present per cross section, ciliary movement, or DNAI1 measured by immunofluorescence in post-treatment bronchial samples.
Interpretation
RCT1100 was generally well tolerated when given at single and multiple doses of 3 and 5 mg in participants with PCD caused by DNAI1 variants.
This abstract is funded by: ReCode Therapeutics