ABX464-104 maintenance study
Research type
Research Study
Full title
A phase 2b, open-label, efficacy and safety study of ABX464 as maintenance therapy in patients with moderate to severe Ulcerative Colitis.
IRAS ID
271100
Contact name
Jimmy Limdi
Contact email
Sponsor organisation
abivax
Eudract number
2019-000733-39
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
1 years, 11 months, 30 days
Research summary
Research Summary
A phase 2b, open-label, efficacy and safety study of ABX464 as maintenance therapy in patients with moderate to severe Ulcerative Colitis.This study is an open-label study which will aim to evaluate the long-term safety and efficacy (how well it works) of the study drug ABX464 in patients with moderate to severe ulcerative colitis (UC) who participated in the ABX464-103 clinical study (induction study) and who are willing to receive treatment with ABX464 as long-term (maintenance) therapy.
All participants (around 232) who have completed the 16-week induction treatment period (ABX464-103) and meet all the inclusion criteria and none of the exclusion criteria outlined in the study protocol will be eligible for this maintenance study.
Participants on this study will be treated for a maximum of 48 weeks in this maintenance study. After the treatment period, patients will be followed for 4 additional weeks for safety purposes.
Participants will be enrolled in approximately 80 to 140 sites located in Europe and Canada.
Lay summary of study results
Disposition and Demography: A total of 217 patients across 14 countries and 69 study centers were enrolled into the study, and 164 patients completed the study. There were 133 male and 84 female patients enrolled, the mean age was 42.1 years with a range of 18 to 75 years.
Efficacy Results: Efficacy results in the study exhibited a favorable efficacy profile over the 96 weeks of study treatment. Study data indicate that at Week 48 and Week 96, a majority of patients achieved clinical response (81.6% and 72.8%, respectively), clinical remission (54.8% and 52.5%, respectively), and endoscopy improvement (61.3% and 59.0%, respectively). Approximately one third of patients achieved endoscopic remission at Week 48 (33.2%) and slightly more achieved this at Week 96 (35.9%).
Safety Results: Overall, ABX464 50 mg daily dose was safe and well-tolerated. The most frequently reported adverse events (AEs) were COVID-19 and aggravation of the underlying ulcerative colitis (UC). The number of patients with treatment emergent adverse events (TEAEs) was 148 (68.2%) patients and 54 of these patients experienced TEAE considered related to investigational product. There were 26 patients who had TEAEs leading to discontinuation of investigational product and 17 patients who had TEAE that led to discontinuation of study. The most frequently reported TEAEs was UC (7 [3.2%]) and the most commonly reported TEAE considered related to investigational product was headache (17[7.8%] patients). In total, 22 patients experienced adverse events of special interest (AESIs), and headache was the most commonly reported AESI.
Post hoc Results: A total of 49 patients achieved clinical remission at Week 8 of the induction study,
38 (77.6%) of these patients had sustained clinical remission. Of the 168 patients who had not achieved clinical remission by Week 8 of the induction study, 81 (48.2%) patients did achieve it by Week 48. Clinical response was achieved by 124 patients by Week 8 of the induction study and 107 (86.3%) of these patients had sustained clinical response at Week 48. Endoscopic remission was achieved by 16 patients at Week 8 of the induction study and 13 (81.3%) of these patients had sustained endoscopic remission at Week 48. Endoscopic improvement was achieved by 70 patients by Week 8 of the induction study and 53 (75.7%) of these patients had sustained endoscopic improvement at Week 48.
Conclusion: In this study, ABX464 50 mg taken orally, QD in patients with moderate to severe active UC exhibited a favorable efficacy and safety profile over 96 weeks of treatment. These results were observed regardless of whether patients were tapered off concomitant treatment with glucocorticosteroids or had prior experience with biologics of JAK inhibitor treatments. The safety profile was favorable and consistent with prior studies with no new AE trends. Combined with the efficacy and safety observed in the double-blind induction trial, ABX464 warrants further exploration in a phase 3 clinical program in patients with moderate to severe active UC.REC name
East Midlands - Nottingham 2 Research Ethics Committee
REC reference
20/EM/0054
Date of REC Opinion
16 Apr 2020
REC opinion
Further Information Favourable Opinion