A Phase 2 Study to Evaluate DNTH103 in Adults With Generalized Myasthenia Gravis (MAGIC)

A Phase 2, Randomized, Blinded, Placebo-Controlled, Study to Evaluate Safety, Tolerability, Pharmacometrics, and Efficacy of DNTH103 in Adults With Generalized Myasthenia Gravis (MAGIC)

The purpose of this Phase 2 study is to evaluate the safety, tolerability, pharmacometrics, and efficacy of DNTH103 in participants with generalized myasthenia gravis (gMG).

The study includes the following periods:

• Screening (up to 10 weeks)
• Randomized, blinded, controlled treatment (RCT) period (13 weeks)
• Open-label extension (OLE) period (optional) for eligible participants (104 weeks)
• Safety follow-up (SFU) (40 weeks)

Inclusion Criteria:

1. Must have given written informed consent before any study-related activities are carried out.

2. Adult males and females, 18 to 75 years of age (inclusive) at Screening.

3. Weight range between 40-120 kg at Screening.

4. Diagnosis of gMG by the following tests:

   Acetylcholine receptor antibody (AChR Ab) positive, and

   One of the following:

   i. History of abnormal neuromuscular transmission test; ii. History of positive anticholinesterase test; iii. Clinical response to acetylcholinesterase inhibitors.

5. Myasthenia Gravis Foundation of America (MGFA) Class II-Iva

6. Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 6 or more

7. Vaccination against N. meningitidis with the quadrivalent meningococcal vaccine, and where available, meningococcal serotype B vaccine within 3 years prior to, or at the time of, initiating study drug.

8. Female participants must:

   Be of non-childbearing potential, or if of childbearing potential, must agree not to donate ova, not to attempt to become pregnant and, if engaging in sexual intercourse with a male partner, must agree to use a highly effective method of contraception.

9. Male participants must be surgically sterile for at least 90 days prior to screening or agree not to donate sperm

Exclusion Criteria:

1. History or presence of significant medical/surgical condition including any acute illness or major surgery considered to be clinically significant

2. Prior history (at any time) of N. meningitidis infection.

3. Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies during Screening.

4. Any thymic surgery/biopsy within 1 year of Screening.

5. Any known or untreated thymoma.

6. Any history of thymic carcinoma or thymic malignancy.

7. Concurrent or previous use of the following medication within the time periods specified below.

   1. Rituximab within 6 months (180 days) prior to randomization (Day 1);
   2. Intravenous immunoglobulin (IVIg) and plasma exchange (PLEX) within 4 weeks (28 days) prior to randomization (Day 1).

8. Participation in another clinical study of an investigational drug within 90 days or 5 half-lives of the investigational agent.