Phase 2 Randomized, Double‑Blind, Placebo‑Controlled Study of Subcutaneous Povetacicept (ALPN‑303) in Adults with Generalized Myasthenia Gravis

The primary objective is to assess the pharmacodynamic effect of povetacicept in adults with generalized myasthenia gravis and to evaluate its safety and tolerability during the double‑blind treatment phase and subsequent long‑term extension.

The trial enrolled 25 subjects diagnosed with generalized myasthenia gravis who met the MGFA clinical classification II‑IV. Eligible participants were adults aged 18 to 80 years and included both females and males; the study also permitted enrollment of individuals classified as vulnerable. All enrolled subjects presented with generalized muscle weakness consistent with the disease definition. While the protocol specified additional inclusion parameters, the primary criteria centered on age and confirmed diagnosis. No specific dietary, physical activity, or habit restrictions were outlined in the available information.

The study is a Phase 2 multicenter trial that randomizes participants in a randomized, double-blind, placebo-controlled design to receive subcutaneous povetacicept or a matching placebo; eligible adults aged 18‑80 with Generalized Myasthenia Gravis classified as MGFA class II‑IV are screened at an initial visit to confirm diagnosis and baseline laboratory values, after which randomization occurs and the first dose is administered; subsequent study visits are scheduled at weeks 4, 8, and 12 to assess the primary pharmacodynamic endpoint (percent change in total IgG) and to monitor safety and tolerability, with an end‑of‑study visit at week 12 for the core phase and optional long‑term extension visits thereafter until the overall trial completion in December 2028; participant involvement therefore spans at least 12 weeks plus any extension period, and early termination may occur due to serious adverse events, withdrawal of consent, major protocol violations, or the need for prohibited concomitant therapy.

The investigational product is ALPN‑303, a povetacicept‑containing solution for injection supplied in a pre‑filled syringe. The pharmaceutical form is a solution for injection, and each dose contains 0 mg of the active substance. The product is administered by subcutaneous injection according to the study’s dosing schedule, with the frequency of administration defined in the protocol.

The control arm receives a matching placebo identified as “Test IMP without active substance.” This investigational medicinal product contains no active pharmaceutical ingredient and is presented in the same appearance as the active product. The placebo is administered by the same route and schedule as the active product to maintain blinding.

Both study treatments are delivered via pre‑filled syringes under aseptic conditions. Dosing visits are scheduled at regular intervals, and the administration is performed by qualified study personnel. Compliance is monitored through documentation of each injection, review of returned syringes, and electronic case report form entries to ensure adherence to the prescribed regimen.

The primary efficacy endpoint is the percent change in total immunoglobulin G (IgG) from baseline to week 12.

Blood samples will be obtained at the screening visit (baseline) and at the week 12 visit. IgG concentrations will be quantified using a laboratory assay, and the percent change will be calculated for each participant to assess the pharmacodynamic effect of povetacicept.