New treatment may reverse coeliac disease

A phase 2a clinical trial demonstrated the proof-of-principle that it is possible to induce immune tolerance to gluten in individuals with coeliac disease. After treatment with investigational drug CNP-101, patients were able to eat gluten with a substantial reduction in inflammation.

Prof. Ciarán Kelly (Harvard Medical School, USA) presented the initial results from the randomised, double-blind, placebo-controlled phase 2a trial which tested CNP-101 8 mg/kg vs placebo in 34 adult coeliac disease patients, assessing the markers of potential efficacy and safety [1]. At inclusion, patients had well-controlled, biopsy-proven coeliac disease, and after inclusion they underwent an oral gluten challenge. Treatments were administered intravenously on day 1 and day 8. The gluten challenge began 7 days after the second treatment administration and included 12 grams of gluten per day for 3 days followed by 6 grams of gluten per day for 11 days.

The primary endpoint was change from baseline in interferon-gamma (IFN-γ) spot-forming units (SFUs) at day 6 after gluten challenge using a gliadin-specific enzyme-linked immunospot assay. This test is a direct measure of gluten-specific systemic T-cell activation in coeliac disease.

The trial met its endpoint when 28 of the patients completed the 14-day gluten challenge protocol, with a mean change from baseline in IFN-γ immunospot assay of 2.10 with CNP-101 and 17.57 with placebo (P=0.0056). Also seen was a trend in protection from small intestinal mucosal damage with deterioration, although not statistically significant. Mean reduction from baseline in villus height to crypt depth ratio was 0.18 with CNP-101 and 0.63 with placebo (P=0.079). Mean change from baseline in intraepithelial lymphocytes was 28.6 with CNP-101 and 35.0 with placebo (P=0.289).

The most frequent adverse events in patients receiving CNP-101 that exceeded the frequency seen in placebo-treated patients were nausea, headache, abdominal pain, and back pain. 6 patients discontinued due to gluten-related symptoms. No patient had clinically significant changes in vital signs, routine clinical labs, or serum cytokines/chemokines, gliadin-specific T-cell proliferation, and cytokine secretion.

Prof. Kelly pointed out that this is the first clinical trial to demonstrate non-autologous induction of antigen-specific immune tolerance in any autoimmune disease.

1. Kelly C et al. CNP-101 prevents gluten challenge induced immune activation in adults with celiac disease. UEG Week Barcelona, Catalonia, Spain, October 19-23, 2019, Abstract LB18.

Posted on 23 October 20198 April 2024