A Phase 3 Study to Evaluate Claseprubart in Adults With Generalized Myasthenia Gravis (EMERGE)

A Phase 3 Global, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Demonstrate the Efficacy, Safety, and Tolerability of Claseprubart (DNTH103) in Patients With Generalized Myasthenia Gravis (EMERGE)

The purpose of this Phase 3 study is to demonstrate the efficacy, safety, and tolerability of claseprubart in participants with generalized myasthenia gravis (gMG).

The study includes the following periods:

• Screening (up to 12 weeks)
• Randomized, blinded, controlled treatment (RCT) period (17 weeks)
• Extended treatment period (ETP) (104 weeks) (optional) for eligible participants [includes blinded extension period (BEP) and open-label extension (OLE) period]
• Safety Follow-Up period (40 weeks)

Inclusion Criteria:

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

2. Weight range between 40-130 kg at Screening

3. Diagnosis of gMG by the following tests:

   1. Acetylcholine receptor antibody (AChR Ab) positive, and
   2. One of the following:

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

4. Myasthenia Gravis Foundation of America (MGFA) Class II-IVa

5. MG-ADL scale score of 6 or more

6. QMG scale score of 10 or more

7. Documented vaccinations against encapsulated bacteria in accordance with local requirements and based on vaccine availability

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 agree not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use an acceptable method of contraception

Exclusion Criteria:

1. History or presence of significant medical/surgical condition including any acute illness, mental illness, or major surgery considered to be clinically significant or that could have potential impact on safety/efficacy or study procedures

2. Known complement deficiency

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

4. Participants with known seropositivity or who test positive for an active viral infection with human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B (HBV; except participants who are seropositive because of HBV vaccination) or hepatitis C virus (HCV) during Screening

5. Previous treatment with claseprubart (DNTH103) or participation in a clinical trial with claseprubart. [

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

7. Any known or untreated thymoma.

8. Any history of thymic carcinoma or thymic malignancy

9. History of active malignancy within 5 years prior to Screening, except basal cell carcinoma of the skin, curatively resected squamous cell carcinoma of the skin, cervical carcinoma in situ curatively treated or low-grade prostate adenocarcinoma for which appropriate management is observation alone

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

    1. Rituximab or other B-cell targeting therapies (ie, inebilizumab) 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)

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

12. Diagnosis of systemic lupus erythematosus (SLE) or family history (defined as a parent, sibling, or child) of SLE