XTMAB-16 Phase 1/2 trial for pulmonary sarcoidosis advances
Enrollment complete in the dose-finding phase of the study
Enrollment is complete in the dose-finding phase of a Phase 1b/2b clinical trial evaluating Xentria’s investigational therapy XTMAB-16 in adults with pulmonary sarcoidosis, and screening for the next phase is expected to start next fall.
The Phase 1b/2 study (NCT05890729) enrolled 39 pulmonary sarcoidosis patients in four countries, exceeding the initial goals for the dose-finding phase, which is testing increasing XTMAB-16 doses against a placebo. The optimal treatment dose and frequency to be tested in the trial’s second phase will be determined by a Data Safety Monitoring Committee based on an analysis of the first part’s data.
“This marks a significant step forward for the sarcoidosis community, bringing us closer to innovative treatment options for this complex disease,” Keith Robinson, MD, medical lead and scientific advisor at Xentria, said in a company press release. “We are encouraged by the momentum of this research and look forward to the insights it will provide, with the potential to shape future treatment strategies and improve patient outcomes.”
Robinson called the milestone “a critical advancement in understanding and addressing pulmonary sarcoidosis.”
In sarcoidosis, clusters of inflammatory cells, called granulomas, form in virtually any place in the body. In pulmonary sarcoidosis, the most common form of the condition, granulomas accumulate in the lungs, which can affect how they work and lead to symptoms like coughing and shortness of breath. If left untreated, pulmonary sarcoidosis can cause scarring and permanent damage to the lungs.
What is XTMAB-16 designed to do?
XTMAB-16, administered directly into the bloodstream, is an antibody that’s designed to suppress the action of TNF-alpha, a protein that plays a key role in the body’s inflammatory response. By blocking TNF-alpha, it should lower inflammation and prevent further granuloma formation.
The therapy received orphan drug status in the U.S. and in Europe for sarcoidosis. This designation is intended to accelerate a therapy’s clinical development and potential regulatory review.
Data from a previous Phase 1 study (NCT04971395) that tested a single infusion of XTMAB-16 at 2 or 4 mg/kg against a placebo in 25 healthy adults showed it was generally well tolerated, with no reports of serious side effects. Headache and stuffy nose were the most commonly reported adverse events, seen only in the 4 mg/kg group. XTMAB-16 remained in the blood for up to about 10 weeks after a single infusion.
Building on these data, the Phase 1b/2 trial’s first dose-finding phase is assessing the safety and tolerability of those two XTMAB-16 doses against a placebo in adults with pulmonary sarcoidosis who are on a stable corticosteroid dose. Corticosteroids are the first-line treatment for sarcoidosis. Because they can cause serious side effects, treatment usually starts at a high dose that’s later reduced.
Participants, who have to be deemed by investigators as able to reduce corticosteroid dosage during the trial, are receiving their assigned treatment every other week or every four weeks for 12 weeks, or about three months.
Secondary goals of the study’s first part include assessing the proportion of patients who reach the targeted reduction in corticosteroids and those who reach at least a 50% reduction.
The second phase, which will enroll up to 62 more patients, is meant to be a proof-of-concept study. Participants will be randomly assigned to receive either XTMAB-16 — at the best dose and frequency established in the first part — or a placebo, for 24 weeks (nearly six months).
Along with continuing to watch for adverse events, researchers will determine the proportion of patients who reach at least a 50% corticosteroid reduction and those who remain at the reduction between weeks 12 and 24.
With enrollment complete in the dose-finding phase, Xentria triggers a milestone payment from its partner Meitheal Pharmaceuticals. Under the partnership signed last year, Xentria has received an upfront payment of $45 million and could receive more than $600 million in future milestones and potential royalties.
Xentria also announced it will present advances in its XTMAB-16 clinical program at the 2025 American Thoracic Society (ATS) conference and ATS Respiratory Innovation Summit, both set for May. It will also join Certara’s upcoming symposium to discuss its use of mathematical models to determine the best design of the ongoing Phase 1b/2a trial.
“These milestones underscore our commitment to advancing transformative treatments for patients living with pulmonary sarcoidosis,” said Noopur Singh, Xentria’s vice president of marketing and patient affairs. “We look forward to engaging with the scientific and medical communities … as we continue to drive innovation in rare disease research.”
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