GLPG1205 for idiopathic pulmonary fibrosis: a phase 2 randomised placebo-controlled trial.

BACKGROUND: GLPG1205 is a selective functional antagonist of G-protein-coupled receptor 84, which plays an important role in fibrotic processes. This study assessed the efficacy, safety and tolerability of GLPG1205 for treatment of idiopathic pulmonary fibrosis (IPF). METHODS: PINTA (ClinicalTrials.gov: NCT03725852) was a phase 2, randomised, double-blind, placebo-controlled, proof-of-concept trial. Patients with IPF were randomised 2:1 to once-daily oral GLPG1205 100 mg or placebo for 26 weeks and stratified to receive GLPG1205 alone or with local standard of care (nintedanib or pirfenidone). The primary end-point was change from baseline in forced vital capacity (FVC); other end-points were safety and tolerability, and lung volumes measured by imaging (high-resolution computed tomography). The study was not powered for statistical significance. RESULTS: In total, 68 patients received study medication. Least squares mean change from baseline in FVC at week 26 was -33.68 (95% CI -112.0-44.68) mL with GLPG1205 and -76.00 (95% CI -170.7-18.71) mL with placebo (least squares mean difference 42.33 (95% CI -81.84-166.5) mL; p=0.50). Lung volumes by imaging declined -58.30 versus -262.72 mL (whole lung) and -33.68 versus -135.48 mL (lower lobes) with GLPG1205 versus placebo, respectively. Treatment with GLPG1205 versus placebo resulted in higher proportions of serious and severe treatment-emergent adverse events and treatment-emergent discontinuations, most apparent with nintedanib. CONCLUSIONS: Treatment with GLPG1205 did not result in a significant difference in FVC decline versus placebo. GLPG1205 demonstrated a poorer safety and tolerability profile than placebo.

Phase 1 and 2 Randomized Clinical Studies Determine Lack of Efficacy for Anti-IL-17C Antibody MOR106 in Moderate-Severe Atopic Dermatitis.

Interleukin 17C (IL-17C) modulates epithelial inflammation and has a possible role in atopic dermatitis (AD) pathology. Four randomized clinical studies (Phase 1 and 2) investigated the safety, tolerability, efficacy, and pharmacokinetic profile of the anti-IL-17C monoclonal antibody MOR106 for up to 12 weeks (NCT03568071: n = 207 adults with moderate-severe AD; NCT03689829 Part 1: n = 32 healthy males; NCT03689829 Part 2: n = 44 adults with moderate-severe AD; and NCT03864627: n = 76 adults with moderate-severe AD). In these studies, MOR106 was either administered intravenously (i.v.) every 2 or 4 weeks at doses between 1-10 mg/kg, or subcutaneously (s.c.), either as a single dose or doses every 2 weeks at 320 mg. Overall, MOR106 was well-tolerated, and the safety profile was consistent with monoclonal antibodies approved for AD. Bioavailability following s.c. dosing was 55%, and steady-state drug levels were reached at 2-4 weeks. Ongoing studies were terminated following a futility analysis of the Phase 2 placebo-controlled dose-finding study (NCT03568071) due to a low probability for achieving the primary efficacy endpoint. Cumulatively, MOR106 demonstrated ineffectiveness for the treatment of AD, but its safety and pharmacokinetic characteristics warrant further drug development in other indications. Funding: sponsored by Galapagos NV; funded by Novartis AG.

Effects of betahistine on patient-reported outcomes in routine practice in patients with vestibular vertigo and appraisal of tolerability: experience in the OSVaLD study.

This was a 3-month multicentre, open-label post-marketing surveillance study of betahistine (24 mg b.i.d. or 16 mg t.i.d.) in patients with vertigo of peripheral vestibular origin. Study endpoints comprised on-treatment changes in the Dizziness Handicap Index (DHI), Hospital Anxiety and Depression Score (HADS) and the Short-Form (SF)-36v2. Total DHI score improved 37.2 points (of a 100-point scale) following betahistine treatment. Corresponding improvements occurred in all three DHI scale domains (all p < 0.001 vs baseline). Betahistine therapy was also accompanied by progressive, significant improvements in both HADS-A and HADS-D scores (p < 0.001), and improvements in the distribution profiles of anxiety and depression scores. Significant improvements in the Physical Component Summary and Mental Component Summary scores of the SF-36v2 were recorded during betahistine treatment. Betahistine was generally well tolerated. A total of 76 adverse drug reactions (ADRs) were recorded in 49 patients (2.4%), of which 75 were classified as mild or moderate and 54 were possibly related to betahistine. ADRs led to study drug discontinuation in 17 patients. These data illustrate that treatment with betahistine 48 mg/day in patients with recurrent peripheral vestibular vertigo is associated with improvements in objective measures of health-related quality of life and satisfactory tolerability.