SAFETY AND EFFICACY OF MH002, AN OPTIMIZED LIVE BIOTHERAPEUTIC PRODUCT, FOR THE TREATMENT OF MILD TO MODERATE ULCERATIVE COLITIS: A FIRST-IN-DISEASE, DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL

Background: Treatment options for patients with mild to moderate ulcerative colitis (UC) failing 5ASA are limited. MH002 is an optimized consortium of 6 nonpathogenic, well characterized commensal bacteria with immunomodulating, wound healing and gut barrier protective effects. This study evaluated the safety, efficacy, and mechanistic effects of MH002 in mild to moderate UC.
Methods: In this 2:1-randomized, double-blind, placebo-controlled first-in-disease study (EudraCT 2020-001355-33), 45 patients with mild to moderate UC (Modified Mayo Score [MMS] =4-8 but including Mayo Endoscopic Subscore [MES] ≥2) received treatment with 400mg MH002 or placebo (PBO) once daily for 8 wks. Full colonoscopies with biopsies were performed at baseline and wk8, biopsies and endoscopy videos were scored by blinded central readers. The primary endpoint was the rate of treatment-emergent adverse events (TEAEs). Exploratory efficacy endpoints included clinical remission (MMS ≤2 with all subscores ≤1 and rectal bleeding subscore =0), endoscopic improvement (MES ≤1), and UC-100 and biomarker normalization (UC-100 ≤25, C reactive protein [CRP] ≤5mg/L, fecal calprotectin [FCP] ≤250mg/kg). Changes from baseline (CFBL) in MES and stool consistency (Bristol Stool Form Scale) were also evaluated.
Results: MH002 was safe and well tolerated: a TEAE was reported in 11/31 (35%) patients with MH002 and in 8/14 (57%) with PBO. Most TEAEs were mild and unrelated to study treatment. Early discontinuations (7/45; 16%) occurred similarly in both groups. At wk8, patients achieved clinical remission, endoscopic improvement, and biomarker improvements at higher rates with MH002 vs PBO (Table 1). Clinical remission rates were 14% for MH002 vs 7% for PBO (Per Protocol Set: 18% vs 0%). Significant differences in favor of MH002 over PBO were seen in the CFBL for MES at wk8 (P=0.05, 1-sided Wilcoxon) and for stool consistency at wk2 (P=0.0057, 1-sided Student t). In total, 14/45 (31%) and 36/42 (86%) patients had elevated CRP and FCP levels at baseline, resp. Of these, more patients treated with MH002 achieved normalization at wk8 (CRP: 60% vs 25%; FCP: 36% vs 15%). Decreases in FCP and stool consistency with MH002 were observed as early as wk2 and were greater than with PBO through wk8 (Fig 1).
Conclusions: MH002 treatment was safe and well tolerated, and resulted in clinically meaningful improvements in disease activity and inflammatory parameters. MH002 therefore represents a promising new treatment for mild to moderate UC patients insufficiently controlled with 5ASA. These results warrant further development in a phase 2/3 study.