Nexvax2 Not Effective Against Acute Gluten-induced Symptoms

Celiac.com 03/22/2023 - ImmusanT, the developers of Nexvax2, have stated that a gluten-free diet alone is not enough to treat celiac disease, as the gut can still be damaged and inflammatory reactions can still occur when gluten is consumed. Nexvax2 is an immunotherapy treatment that uses specific peptides to modify gluten-induced symptoms in celiac disease.

A team of researchers recently set out to conduct a phase 2 trial, funded by ImmusanT, to investigate the effects of Nexvax2 on immune activation and gluten-induced symptoms in celiac disease patients. 

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The research team included Jason A Tye-Din, PhD; A James M Daveson, MBBS; Gautam Goel, PhD; Kaela E Goldstein, BS; Holly L Hand; Kristin M Neff, BS; Alina Popp, MD; Juha Taavela, MD; Prof Markku Maki, MD; Prof Jorma Isola, PhD; Leslie J Williams, BS; Kenneth E Truitt, MD; Robert P Anderson, PhD, on behalf of theRESET CeD Study Group.

They are variously affiliated with the Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC, Australia; the Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia; the Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, VIC, Australia; and the Centre for Food & Allergy Research, Infection and Immunity, Murdoch Children's Research Institute, Parkville, VIC, Australia.

About The Study

The trial was randomized, double-blind, and placebo-controlled, conducted across 41 sites in the USA, Australia, and New Zealand. Patients aged 18-70 with celiac disease, who had excluded gluten from their diet for at least a year, were HLA-DQ2.5 positive, and had experienced worsening symptoms after consuming 10 grams of gluten, were included in the study. Patients were split into homozygous and non-homozygous groups based on their HLA-DQ2.5 status.

Patients in the non-homozygous group were randomly assigned to receive either subcutaneous Nexvax2 or a saline placebo twice a week. The doses were gradually increased from 1 μg to 750 μg during the first 5 weeks, followed by 11 weeks of maintenance therapy at 900 μg per dose. Patients in the exploratory homozygous group were randomly assigned to receive either Nexvax2 or a placebo, with the same dosage as the non-homozygous group.

The primary endpoint of the trial was to measure the change in celiac disease patient-reported total gut-related outcomes from baseline to the day of a masked 10-gram gluten challenge given in week 14, analyzed in the non-homozygous intention-to-treat population. The team screened 383 volunteers, out of which 179 patients were analyzed, with one excluded due to mis-assignment of genotype.

After an interim analysis of 66 non-homozygous patients, the study was discontinued. An unmasked post-hoc analysis was conducted on all available data for the primary endpoint and secondary symptom-based endpoints, combining data from 67 patients. The average change in total gastrointestinal score from baseline to the day of the first masked gluten challenge was 2.86 for the non-homozygous Nexvax2 group, compared to 2.63 for the non-homozygous placebo group. 

Nexvax2 Did Not Reduce Acute Gluten-induced Symptoms

The adverse events reported in patients who received Nexvax2 and placebo were similar, with the most common being nausea, followed by diarrhea, abdominal pain, headache, and fatigue. Serious adverse events were reported in five out of 178 patients, including two out of 92 who received Nexvax2 and three out of 82 who received placebo. During the gluten challenge, one patient in the non-homozygous Nexvax2 group experienced a serious muscle strain with imaging that indicated a partial kidney infarction.

In conclusion, the trial showed that Nexvax2 did not reduce acute gluten-induced symptoms, and that a masked bolus vital gluten challenge could provide an alternative to extended gluten challenges in efficacy studies for celiac disease.

Read more in thelancet.com