Clinical trial NCT06282159: A Phase 2 Study to Evaluate DNTH103 in Adults With Generalized Myasthenia Gravis (MAGIC)
Official title: A Phase 2, Randomized, Blinded, Placebo-Controlled, Study to Evaluate Safety, Tolerability, Pharmacometrics, and Efficacy of DNTH103 in Adults With Generalized Myasthenia Gravis (MAGIC)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Myasthenia Gravis, Generalized
Lead sponsor: Dianthus Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-02-28
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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 (52 weeks)
* Safety follow-up (40 weeks)

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs)
timeFrame: Baseline (Day 1) to Week 13
Secondary outcomes:
measure: Change from Baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale Score
timeFrame: Baseline (Day 1) to Week 13
measure: Change from Baseline in Quantitative Myasthenia Gravis (QMG) Scale Score
timeFrame: Baseline (Day 1) to Week 13
measure: Change from Baseline to Week 13 in Myasthenia Gravis Composite (MGC) Scale Score
timeFrame: Baseline (Day 1) to Week 13
measure: Incidence of TEAEs and Treatment-Emergent SAEs
timeFrame: Baseline (Day 1) up to Week 52 of the OLE
measure: Serum Concentrations of DNTH103
timeFrame: Baseline (Day 1) to Week 52 of the OLE
measure: Change from Baseline in Complement Total Blood Test (CH50)
timeFrame: Baseline (Day 1) to Week 52 of the OLE
measure: Incidence and Titer of Antidrug Antibody (ADAs) Against DNTH103
timeFrame: Baseline (Day 1) to Week 52 of the OLE
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Clinical Study Site
state: Arizona
city: Irvine
country: United States
facility: Clinical Study Site
state: California
city: Stamford
country: United States
facility: Clinical Study Site
state: Connecticut
city: Boca Raton
country: United States
facility: Clinical Study Site
state: Florida
city: Bradenton
country: United States
facility: Clinical Study Site
state: Florida
city: Maitland
country: United States
facility: Clinical Study Site
state: Florida
city: Tampa
country: United States
facility: Clincal Study Site
state: Florida
city: O'Fallon
country: United States
facility: Clinical Study Site
state: Illinois
city: Kansas City
country: United States
facility: Clinical Study Site
state: Kansas
city: Lexington
country: United States
facility: Clinical Study Site
state: Kentucky
city: Boston
country: United States
facility: Clinical Study Site
state: Massachusetts
city: East Lansing
country: United States
facility: Clinical Study Site
state: Michigan
city: Columbia
country: United States
facility: Clinical Study Site
state: Missouri
city: Cincinnati
country: United States
facility: Clinical Study Site
state: Ohio
city: Columbus
country: United States
facility: Clinical Study Site
state: Ohio
city: Dallas
country: United States
facility: Clinical Study Site
state: Texas
city: Dallas
country: United States
facility: Clinical Study Site
state: Texas
city: Houston
country: United States
facility: Clinical Study Site #2
state: Texas
city: Houston
country: United States
facility: Clinical Study Site
state: Texas
city: Lubbock
country: United States
facility: Clinical Study Site
state: Texas
city: Richmond
country: United States
facility: Clinical Study Site
state: Virginia
city: San Miguel de Tucuman
country: Argentina
facility: Clinical Study Site
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Clinical Study Site
city: Buenos Aires
country: Argentina
facility: Clinical Study Site
city: Buenos Aires
country: Argentina
facility: Clinical Study Site
city: Cordoba
country: Argentina
facility: Clinical Study Site
city: Rosario
country: Argentina
facility: Clinical Study Site
city: London
country: Canada
facility: Clinical Study Site
state: Ontario
city: Ostrava
country: Czechia
facility: Clinical Study Site
city: Copenhagen
country: Denmark
facility: Clinical Study Site
city: Bordeaux Cedex
country: France
facility: Clinical Study Site
city: Nice
country: France
facility: Clinical Study Site
city: Strasbourg
country: France
facility: Clinical Study Site
city: Haifa
country: Israel
facility: Clinical Study Site
city: Ramat Gan
country: Israel
facility: Clinical Study Site
city: Zefat
country: Israel
facility: Clinical Study Site
city: Milano
country: Italy
facility: Clinical Study Site
city: Napoli
country: Italy
facility: Clinical Study Site
city: Pisa
country: Italy
facility: Clinical Study Site
city: Rome
country: Italy
facility: Clinical Study Site
city: Rome
country: Italy
facility: Clinical Study Site
city: Amsterdam
country: Netherlands
facility: Clinical Study Site
city: Skopje
country: North Macedonia
facility: Clinical Study Site
city: Bergen
country: Norway
facility: Clinical Study Site
city: Bydgoszcz
country: Poland
facility: Clinical Study Site
city: Katowice
country: Poland
facility: Clinical Study Site
city: Krakow
country: Poland
facility: Clinical Study Site
city: Kraków
country: Poland
facility: Clinical Study Site
city: Lublin
country: Poland
facility: Clinical Study Site
city: Warsaw
country: Poland
facility: Clinical Study Site
city: Warsaw
country: Poland
facility: Clinical Study Site
city: Belgrade
country: Serbia
facility: Clinical Study Site
city: Kragujevac
country: Serbia
facility: Clinical Study Site
city: Nis
country: Serbia
facility: Clinical Study Site
city: Novi Sad
country: Serbia
facility: Clinical Study Site
city: Malmö
country: Sweden
facility: Clinical Study Site
Study officials:
References: