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

Myasthenia Gravis, Generalized Clinical Trial

— 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06282159
• Other study ID #: DNTH103-MG-201
• Status: Recruiting
• Phase: Phase 2
• Start date: February 23, 2024
• Est. completion date: December 2027

Study information

• Verified date: June 2024
• Source: Dianthus Therapeutics
• Contact: Sammie Kaligotla
• Phone: 929-999-4055
• Email: clinicaltrials[@]dianthustx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2027
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 nonchildbearing 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.

Related Conditions & MeSH terms

• Muscle Weakness
• Myasthenia Gravis
• Myasthenia Gravis, Generalized

Intervention

Drug:
• DNTH103
Day 1: IV loading dose Week 1 to Week 11: DNTH103 administered SC every 2 weeks
• Placebo
Day 1: IV infusion of placebo Week 1 to Week 11: placebo administered SC every 2 weeks

Locations

Country	Name	City	State
United States	Clinical Study Site	Bradenton	Florida
United States	Clinical Study Site	Dallas	Texas
United States	Clinical Study Site	Houston	Texas
United States	Clinical Study Site	Lubbock	Texas
United States	Clinical Study Site	Stamford	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Dianthus Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence, severity, and relationship of TEAEs (including treatment discontinuation due to adverse events [AEs]) [Time Frame: Baseline (Day 1) to Safety Follow-Up Visit (up to Week 40)]	An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporarily associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational product).	Baseline (Day 1) to Safety Follow-Up Visit (up to Week 40)
Primary	Incidence, severity, and relationship of adverse events of special interest (AESI)	An adverse event of special interest (AESI) (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product, for which ongoing monitoring and rapid communication by the investigator to the sponsor may be appropriate. Such an event may require further investigation in order to characterize and understand it. Depending on the nature of the event, rapid communication by the trial sponsor to other parties may also be needed (e.g., regulators)	Baseline (Day 1) to Safety Follow-Up Visit (up to Week 40)
Primary	Number of participants with changes from baseline in ECG parameters	Number of participants with changes in ECG values during the study period will be reported	Baseline (Day 1) to Safety Follow-Up Visit (up to Week 40)
Primary	Number of participants with changes in clinical laboratory values over time	Number of participants with changes in clinical laboratory values during the study period will be reported	Baseline (Day 1) to Safety Follow-Up Visit (up to Week 40)
Secondary	Change from baseline 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 13
Secondary	Change from baseline in Quantitative Myasthenia Gravis (QMG) scale score	The MGC is a validated assessment tool for measuring clinical status of patients with MG. The range of total MGC score is 0 to 50 and 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 13
Secondary	Serum concentrations of DNTH103	Blood samples will be collected for measurement of serum concentrations of DNTH103 at various timepoints both pre- and post-dose.	Baseline (Day 1) to Week 13
Secondary	Change from baseline in complement total blood test (CH50)	Blood samples will be collected to determine changes in CH50 at various timepoints	Baseline (Day 1) to Week 13
Secondary	Antidrug antibody (ADA) levels against DNTH103	Blood samples will be collected to measure ADA against DNTH103 at various timepoints	Baseline (Day 1) to Week 13