Study design
Nakajo-Nishimura, AGS, vasculopathy, lipodystrophy, neutrophilic dermatosis
RECRUITMENT, LIPODYSTROPHY, NEUTROPHILIC DERMATOSIS
This Phase 2/3, multicenter, open-label study (ClinicalTrials.gov Identifier: NCT04517253) evaluated the efficacy and safety of baricitinib in adult and pediatric Japanese patients with autoinflammatory type I interferonopathies including NNS/CANDLE, SAVI, and AGS.The study was divided into 6 periods including (i) screening, (ii) pre-treatment (only for patients with NNS/CANDLE), (iii) dose adjustment, (iv) primary treatment, (v) maintenance treatment, and (vi) post-treatment follow-up period (Fig. Study design. AGS = Aicardi-Goutières syndrome; NNS/CANDLE = Nakajo-Nishimura syndrome/chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature; SAVI = STING-associated vasculopathy with onset during infancy; STING = stimulator of interferon genes; V = visit; wk = week. The screening period varied for patients with NNS/CANDLE, SAVI, and AGS. The screening period ranged from 7 to 35 days prior to baseline (Visit 6) for patients with SAVI and AGS, whereas patients with NNS/CANDLE had a screening period of 1 week (Visit 1) before entering the pre-treatment period.Patients with NNS/CANDLE entered a 12-week pre-treatment period at the beginning of Visit 1. The data from the pre-treatment period was used for baseline comparison.Patients who met all eligibility criteria entered the 8-week dose adjustment period (Visit 6 to Visit 9). Patients initially received treatment dose based on weight class and eGFR, which was further escalated to identify tolerable dose. The dose escalation model was based on the results from previous PK studies of baricitinib [Patients received the optimized dosage throughout the primary and maintenance treatment periods. The duration of primary treatment period was 12 weeks for patients with NNS/CANDLE and 24 weeks for patients with SAVI and AGS based on the results from the JAGA (NCT01724580) trial [Treatment period was considered from the first dose of baricitinib (Visit 6; Week 0) to the date of final visit or early discontinuation period. Endpoint of post-follow-up period was Visit 801. Primary endpoint assessed the change in mean DDS from baseline (Week 0; Visit 6) to Week 20 in patients with NNS/CANDLE and Week 32 in patients with SAVI and AGS. Other efficacy and safety endpoints were assessed until Week 52.The study protocol was approved by the institutional review boards prior to patient recruitment, and each patient or their guardian provided written informed consent prior to enrollment. The study was conducted in accordance with consensus ethics principles derived from international ethics guidelines, including the Declaration of Helsinki and the International Ethical Guidelines by the Council for International Organizations of Medical Sciences and the International Council for Harmonization E6 Guidelines for Good Clinical Practice.