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Phase 3 CIDP Trial Shows a 75% Response Rate at First Look: Claseprubart’s Real Test Is Whether Efficacy Holds After Withdrawal
Among the first 40 patients who completed open-label treatment in the CAPTIVATE trial, 30 met the prespecified response criteria; the figure exceeded the company’s threshold but cannot yet substitute for randomized, placebo-controlled relapse results.
Chronic inflammatory demyelinating polyneuropathy (CIDP) progressively weakens strength and sensation in the limbs, and treatment often requires long-term suppression of an uncontrolled immune response. Dianthus Therapeutics announced a preliminary analysis of the Phase 3 CAPTIVATE trial: among the first 40 patients who completed the first stage of treatment, 30 met the response criteria, for a response rate of 75%, exceeding the company’s prespecified target of 50%.
The investigational drug claseprubart (DNTH103) is a monoclonal antibody that inhibits the complement protein C1s. It is intended to intercept nerve damage caused by the classical complement pathway while preserving other complement defense functions. The first stage of CAPTIVATE uses an open-label design, with patients receiving treatment for up to 13 weeks; the registry defines response as an improvement of at least 1 point on the adjusted INCAT disability scale.
Among these 40 patients, in addition to the 30 confirmed responders, 5 relapsed and 5 remained stable. Company data showed that responders had a mean 1.6-point reduction in adjusted INCAT score, a 15.9-kilopascal increase in grip strength, a 5.1-point improvement in the Medical Research Council sum score, and an 8.9-point increase on the I-RODS daily activity scale. The consistent direction across multiple measures supports drug activity, but the analytical sample remains small and the data have not yet been finalized.
The safety update found no treatment-related serious infections, serious adverse events, or treatment discontinuations due to safety issues, and no clinical symptoms of drug-induced lupus were observed. This is particularly important for a long-term complement-inhibiting therapy, although the available data are insufficient to rule out less common risks or those that emerge only as exposure duration increases.
The 75% figure also cannot be interpreted directly as proof that the drug has demonstrated efficacy in a Phase 3 trial. The first stage has no placebo group, investigators and patients know which treatment is being used, and this analysis covers only the first 40 patients to complete treatment; natural fluctuations, patient selection, and assessment bias could all affect the apparent response rate.
The truly decisive part is the second stage. Patients who meet the response criteria will be randomized under double-blind conditions to receive either 300 mg of claseprubart or placebo every two weeks and will be followed for up to 52 weeks; the primary endpoint is the time from the start of the second stage to relapse, defined as a worsening of at least 1 point on adjusted INCAT. In other words, the trial must not only show that patients can improve, but also determine whether withdrawing effective treatment creates a divergence in relapse risk compared with patients who continue therapy.
The amended study design is expected to enroll up to 256 patients in the first stage and allow 128 responders to enter the second stage. The current signal has crossed the company’s early threshold, but it remains only the first half of the full validation chain; until the randomized controlled results are available, whether claseprubart can provide durable and clinically meaningful control of CIDP remains unresolved.