Evaluation of NMD670 Efficacy, Safety, and Tolerability in Adult Patients with AChR/MuSK-Ab+ Myasthenia Gravis: A Phase 2b Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this Phase 2b, randomized, double-blind, placebo-controlled study is to assess the **dose response** of NMD670 on clinical efficacy in adult patients with **Myasthenia Gravis** who are positive for AChR/MuSK antibodies. This evaluation is clinically relevant as it aims to determine the optimal dosing regimen of NMD670, which could potentially improve the management of Myasthenia Gravis by enhancing muscle strength and reducing symptoms associated with this autoimmune neuromuscular disorder.

The clinical trial involves a total of **42 participants** diagnosed with **Myasthenia Gravis**. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a documented positive AChR or MuSK antibody test and must be classified under MGFA class II, III, or IV. The trial population was selected based on specific criteria, including the ability to swallow tablets and a body mass index between 18 and 35 kg/m², with a minimum weight of 40 kg. Both male and female participants of childbearing potential are required to use highly effective contraception methods during the study. The trial includes a vulnerable population, and all participants have provided informed consent. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is a **Phase 2b**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, and tolerability of three dose levels of **NMD670** over a period of 21 days in adult patients diagnosed with **Myasthenia Gravis**. The primary objective is to assess the dose response of NMD670 on clinical efficacy as rated by clinicians, with the primary endpoint being the change from baseline to day 21 in the quantitative myasthenia gravis (QMG) total score for NMD670 compared to placebo. The trial is expected to commence recruitment on August 1, 2024, and conclude by September 30, 2025.

Participants will be randomly assigned to receive either NMD670 or a placebo, administered orally in tablet form. The study will include several key visits: an initial screening visit to confirm eligibility based on criteria such as age, diagnosis, and antibody test results; baseline assessments; and subsequent follow-up visits to monitor safety and efficacy. The end-of-study visit will occur on day 21, marking the completion of the treatment period. Participants are expected to be involved in the study for the entire 21-day treatment period unless early termination is warranted due to adverse events, withdrawal of consent, or protocol non-compliance.

Inclusion criteria require participants to be adults aged 18 years or older with a confirmed diagnosis of Myasthenia Gravis, specifically MGFA class II, III, or IV, and a documented positive AChR or MuSK antibody test. Participants must be able to swallow tablets and meet specific body mass index and weight requirements. Both male and female participants of childbearing potential must agree to use highly effective contraception during the study. The trial excludes individuals who do not meet these criteria or who have conditions that could interfere with the study's objectives.

The clinical trial involves the administration of **NMD670**, an investigational medication, in the form of a **tablet**. The active substance, also named **NMD670**, is of chemical origin and is provided by NMD PHARMA A/S. The medication is administered orally, with a maximum daily dose of 800 mg and a total maximum dose of 16,800 mg over a treatment period of 21 days. The trial aims to evaluate the efficacy, safety, and tolerability of three dose levels of NMD670 in adult patients with AChR/MuSK-Ab+ **Myasthenia Gravis**. Participant compliance with the dosing schedule will be monitored throughout the study.

In addition to the experimental treatment, a **placebo** is used as a comparator in this double-blind, placebo-controlled study. The placebo is administered in a similar pharmaceutical form and route as the experimental medication, ensuring blinding is maintained. The placebo does not contain any active substance and serves to assess the efficacy of NMD670 by providing a baseline for comparison. The use of a placebo is critical in determining the true therapeutic effect of the investigational drug.

The efficacy of the investigational product, **NMD670**, in the treatment of **Myasthenia Gravis** will be assessed in a Phase 2b, randomized, double-blind, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the change from baseline to day 21 in the quantitative myasthenia gravis (QMG) total score for NMD670 compared to placebo. This endpoint will be measured using a validated scale that quantifies the severity of myasthenia gravis symptoms. The trial is designed to assess the dose response of NMD670 on clinical efficacy as rated by clinicians. The study will involve adult patients with a documented positive AChR or MuSK antibody test, and the treatment period will last for 21 days. The efficacy assessments will be conducted at specified time points, with the primary focus on the change in QMG total score by the end of the treatment period.