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).

Study Overview

• Status: Not yet recruiting
• Conditions: Myasthenia Gravis, Generalized
• Intervention / Treatment: Drug: Placebo; Combination product: Placebo; Drug: Claseprubart; Combination product: Claseprubart

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Estimated): 195
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Dianthus Clinical Contact Center; Phone Number: 929-999-4055; Email: clinicaltrials@dianthustx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Intravenous (IV) infusion of Placebo on Day 1 followed by subcutaneous (SC) injections of Placebo every 2 weeks (Q2W) starting at Week 1 (Day 8).	Drug: Placebo; IV infusion on Day 1; Combination product: Placebo; Prefilled syringe containing placebo for SC administration
Experimental: Claseprubart Q2W; IV loading dose of claseprubart on Day 1 followed by SC injections of claseprubart Q2W starting at Week 1 (Day 8).	Drug: Claseprubart; IV loading dose on Day 1; Other Names: DNTH103; Combination product: Claseprubart; Prefilled syringe containing claseprubart for SC administration
Experimental: Claseprubart Every 4 weeks (Q4W); IV loading dose of claseprubart on Day 1 followed by SC injections of claseprubart or Placebo Q2W starting at Week 1 (Day 8), with doses alternating between claseprubart and placebo.	Combination product: Placebo; Prefilled syringe containing placebo for SC administration; Drug: Claseprubart; IV loading dose on Day 1; Other Names: DNTH103; Combination product: Claseprubart; Prefilled syringe containing claseprubart for SC administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline to Week 17 in Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale Score	The MG-ADL score is an 8-item patient reported outcome (PRO) instrument. The MG-ADL targets symptoms of disability across ocular, bulbar, respiratory, and axial symptoms. The item responses are scored from 0 to 3, and the total score of the MG-ADL is the sum of the 8 items and ranges from 0 to 24, with a higher score indicating more disability.	Baseline (Day 1) to Week 17

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline to Week 17 in Quantitative Myasthenia Gravis (QMG) Scale Score	The QMG is a clinician-reported assessment to evaluate muscle strength. The QMG consists of 13 items that measure endurance or fatiguability, with each item having a possible score that ranges from 0 - 3. The total possible QMG scores range from 0 - 39, with a higher score indicating greater disease burden.	Baseline (Day 1) to Week 17
Change from Baseline to Week 17 in Myasthenia Gravis Composite (MGC) Scale Score	The MGC is a validated assessment tool for measuring clinical status of participants with MG. The range of total MGC score is 0 to 50, with higher scores indicating more severe disease. A clinically meaningful improvement is reflected by a 3-point improvement in MGC score. The MGC assesses 10 important functional areas most frequently affected by MG and the scales are weighted for clinical significance that incorporates patient-reported outcomes.	Baseline (Day 1) to Week 17
Proportion of Participants with Greater Than or Equal to (≥) a 5-point Reduction in MG-ADL Scale Score at Week 17 Compared to Baseline		Baseline (Day 1) to Week 17
Proportion of Participants Who Reach Minimal Symptom Expression (MSE), Defined as MG-ADL 0 or 1 at Week 17, Without Use of Rescue Therapy		Baseline (Day 1) to Week 17
Proportion of Participants with a ≥ 5-point Reduction in QMG Scale Score at Week 17 Compared to Baseline		Baseline (Day 1) to Week 17
Incidence of Treatment-emergent Adverse Events (TEAEs) and Treatment-Emergent and Treatment-Emergent Serious Adverse Events (SAEs) in the RCT period, BEP, OLE, and Safety Follow-Up	Number of participants with TEAEs and treatment-emergent SAEs will be reported.	Baseline (Day 1) through Safety Follow-Up period (up to approximately 161 weeks)
Serum Concentrations of Claseprubart	Blood samples will be collected for measurement of serum concentrations of claseprubart at various timepoints both pre- and post-dose.	Baseline (Day 1) through Safety Follow-Up period (up to approximately 161 weeks)
Change from Baseline in Complement Total Blood Test (CH50) in Serum ex vivo	Blood samples will be collected to determine changes in CH50 at various timepoints.	Baseline (Day 1) through Safety Follow-Up period (up to approximately 161 weeks)
Incidence of Antidrug Antibody (ADAs) Against Claseprubart in the RCT Period, BEP, OLE, and Safety Follow-Up	Blood samples will be collected to measure ADA against claseprubart at various timepoints.	Baseline (Day 1) through Safety Follow-Up period (up to approximately 161 weeks)
Titer of ADAs Against Claseprubart in the RCT Period, BEP, OLE, and Safety Follow-Up	Blood samples will be collected to measure ADA against claseprubart at various timepoints.	Baseline (Day 1) through Safety Follow-Up period (up to approximately 161 weeks)

Collaborators and Investigators

• Sponsor: Dianthus Therapeutics

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): September 1, 2031

Study Registration Dates

• First Submitted: May 27, 2026
• First Submitted That Met QC Criteria: June 9, 2026
• First Posted (Actual): June 15, 2026

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myasthenia Gravis
• Other Study ID Numbers: DNTH103-MG-301; 2026-525298-38-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No