Myasthenia Gravis, Generalized
Conditions
Brief summary
The purpose of this Phase 3 study is to demonstrate the efficacy, safety, and tolerability of claseprubart in participants with generalized myasthenia gravis (gMG).
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)
Interventions
DRUGClaseprubart
IV loading dose on Day 1
DRUGPlacebo
IV infusion on Day 1
Sponsors
Dianthus Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline to Week 17 in Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale Score | Baseline (Day 1) to Week 17 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline to Week 17 in Quantitative Myasthenia Gravis (QMG) Scale Score | Baseline (Day 1) to Week 17 | 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. |
| Change from Baseline to Week 17 in Myasthenia Gravis Composite (MGC) Scale Score | Baseline (Day 1) to Week 17 | 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. |
| 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 | Baseline (Day 1) through Safety Follow-Up period (up to approximately 161 weeks) | Number of participants with TEAEs and treatment-emergent SAEs will be reported. |
| Serum Concentrations of Claseprubart | Baseline (Day 1) through Safety Follow-Up period (up to approximately 161 weeks) | Blood samples will be collected for measurement of serum concentrations of claseprubart at various timepoints both pre- and post-dose. |
| Change from Baseline in Complement Total Blood Test (CH50) in Serum ex vivo | Baseline (Day 1) through Safety Follow-Up period (up to approximately 161 weeks) | Blood samples will be collected to determine changes in CH50 at various timepoints. |
| Incidence of Antidrug Antibody (ADAs) Against Claseprubart in the RCT Period, BEP, OLE, and Safety Follow-Up | Baseline (Day 1) through Safety Follow-Up period (up to approximately 161 weeks) | Blood samples will be collected to measure ADA against claseprubart at various timepoints. |
| Titer of ADAs Against Claseprubart in the RCT Period, BEP, OLE, and Safety Follow-Up | Baseline (Day 1) through Safety Follow-Up period (up to approximately 161 weeks) | Blood samples will be collected to measure ADA against claseprubart at various timepoints. |
Countries
United States
Contacts
CONTACTDianthus Clinical Contact Center
Outcome results
None listed