WASHINGTON — AMG 715, an investigational anti-interleukin 15 inhibitor, showed safety and efficacy for stopping the progression of refractory celiac disease type II, according to phase 2 randomized controlled trial data presented at DDW 2018.
“This ... human monoclonal antibody ... may be a promising experimental treatment for refractory celiac disease type II,” Christophe Cellier, MD, PhD, of Hôpital Européen Georges Pompidou, Paris, said during his presentation. “This study is a proof of concept with clinically meaningful differences.”
Refractory celiac disease type II, also known as pre-enteropathy-associated T cell lymphoma, is “a rare and devastating small bowel in situ lymphoma which primarily arises as a complication of celiac disease,” according to the study abstract. These patients have a poor prognosis, with half progressing to enteropathy-associated T cell lymphoma, which has about a 45% 5-year survival rate.
No treatments are currently approved for this condition, and the rationale for AMG 715 stems from the knowledge that interleukin 15 exerts anti-apoptotic effects on aberrant intra-epithelial lymphocytes.
To evaluate the efficacy of AMG 715 for halting progression of refractory celiac disease type II, Cellier and colleagues randomly assigned 28 patients to receive 8 mg/kg of the study drug or placebo, administered intravenously seven times over 10 weeks.
Patients were evaluated by upper endoscopy and biopsy before and after treatment at week 12. Among these patients, 19 met criteria for “pure” refractory celiac disease type II.
Cellier noted that “the primary efficacy endpoint was not met,” as the study drug failed to achieve significant reduction in intestinal aberrant intra-epithelial lymphocytes (IELs). However, the study drug did show efficacy for halting disease progression and benefits in other endpoints.
“One of the most promising results of our study,” he said, was that all patients who received the study drug were stable or showed reductions in T cell receptor (TcR) clonality from baseline to week 12 (P = .02). In contrast, TcR clonality increased in 33% of placebo patients in the per protocol analysis and in 50% of placebo patients in the “pure” population.
Further, the per-protocol population showed a reduction — though non-significant — in the proportion of small-bowel aberrant IELs after treatment with the study drug, with a 2.45% increase from baseline vs. a 7.3% increase in the placebo group. “Pure” refractory celiac disease type II patients showed similar reductions (0% vs. 14%).
There was a trend toward improved intestinal histology vs. placebo. Villous atrophy improved by 27% (vs. 0% with placebo) in the “pure” patients, and by 26.4% vs. 15.7% in the per-protocol population.
There was also significant improvement in diarrhea vs. placebo (P < .001). Bristol Stool Form Scale scores showed an increase in weeks with diarrhea among the placebo group, while the study drug group showed reductions (P < .01).
“The safety profile was acceptable for this very sick population,” Cellier said. Overall, six serious adverse events occurred (5 with the study drug). Mild nasopharyngitis was the most common adverse reaction in the study drug group.
Cellier noted they observed no immunogenicity with the study drug.
A longer and larger phase 3 study is planned, he said, as these data show the agent provides “hope for preventing lymphoma in refractory celiac disease type II.”
This drug also showed potential for protecting patients with celiac disease from inadvertent gluten exposure in a separate study presented here. – by Adam Leitenberger
Cellier C, et al. Abstract 616. Presented at: Digestive Disease Week; June 2-5, 2018; Washington, D.C.
Disclosures: Cellier reports financial relationships with Amgen and Cellimmune, which funded the study. Please see the DDW faculty disclosure index for a list of all other authors’ relevant financial disclosures.