DNTH103 for Myasthenia Gravis

(MAGIC Trial)

Recruiting in Palo Alto (17 mi)

+59 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Dianthus Therapeutics

Must not be taking: Rituximab, IVIg, PLEX

Disqualifiers: HIV, Hepatitis B, Thymoma, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used Rituximab within 6 months or IVIg and plasma exchange within 4 weeks before starting the trial.

What data supports the effectiveness of the drug DNTH103 for treating myasthenia gravis?

Recent advances in drug therapy for myasthenia gravis have significantly improved the quality of life for many patients, reducing complications and hospitalizations. While specific data on DNTH103 is not provided, the approval of similar treatments like complement and FcRN inhibitors by the FDA suggests potential effectiveness in managing the condition. ^{1 2 3 4 5}

How does the drug DNTH103 differ from other treatments for myasthenia gravis?

DNTH103 is unique because it is an antisense oligonucleotide that targets acetylcholinesterase (AChE) mRNA, potentially reducing AChE activity and improving muscle function in myasthenia gravis. This mechanism is different from other treatments like pyridostigmine, which directly inhibits AChE, and eculizumab, which targets the complement system. ^{6 7 8 9 10}

Research Team

Eligibility Criteria

Adults aged 18-75 with generalized myasthenia gravis (gMG), a muscle weakness condition, can join this trial. They must have an MG-ADL score of 6+, be AChR antibody positive, and fall within the MGFA Class II-Iva. Participants need to agree to contraception if applicable and should weigh between 40-120 kg.

Inclusion Criteria

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

My weight is between 40 and 120 kg.

I am between 18 and 75 years old.

Exclusion Criteria

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

I have a significant health condition or had major surgery recently.

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

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 10 weeks

Randomized, blinded, controlled treatment (RCT)

Participants receive either DNTH103 or placebo to evaluate safety, tolerability, pharmacometrics, and efficacy

13 weeks

Open-label extension (OLE)

Eligible participants may opt into continuation of treatment with DNTH103 long-term

52 weeks

Safety follow-up

Participants are monitored for safety and effectiveness after treatment

40 weeks

Treatment Details

Interventions

• DNTH103 (Monoclonal Antibodies)

Trial Overview The study is testing DNTH103's safety and effectiveness for gMG patients compared to a placebo. It will look at how well the drug works, its side effects, and how it moves through the body.

Participant Groups

Group I: DNTH103 low dose Q2W Experimental Treatment 1 Intervention

Group II: DNTH103 high dose Q2W Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

West Texas Neurology Clinic Lubbock, TX

Clinical Study Site Stamford, CT

Texas Neurology Dallas, TX

Clinical Study Site Bradenton, FL

More Trial Locations

Who Is Running the Clinical Trial?

Dianthus Therapeutics

Lead Sponsor

Trials

3

Patients Recruited

580+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline Decrement in Patients with Mild Myasthenia Gravis Predicts Immunomodulation Treatment. Abraham, A., Lovblom, LE., Bril, V.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myasthenia Gravis. Lisak, RP.[2022]

The FDA has recently approved new therapies, including complement and Fc receptor inhibitors, for treating generalized myasthenia gravis, highlighting advancements in treatment options for this condition.

There is ongoing uncertainty regarding which patients will benefit most from these expensive therapies, prompting discussions on the need for better clinical trial readiness and biomarker development to guide future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The best and worst of times in therapy development for myasthenia gravis. Benatar, M., Cutter, G., Kaminski, HJ.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myasthenia gravis: subgroup classification and therapeutic strategies. Gilhus, NE., Verschuuren, JJ.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological Management of Myasthenia Gravis: A Century of Expert Opinions in Cecil Textbook of Medicine. Manu, P., Rogozea, LM., Roman-Filip, C.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Further developments with antisense treatment for myasthenia gravis. Sussman, J., Argov, Z., Wirguin, Y., et al.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stimulated-single fiber electromyography monitoring of anti-sense induced changes in experimental autoimmune myasthenia gravis. Boneva, N., Hamra-Amitay, Y., Wirguin, I., et al.[2007]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppression of experimental autoimmune myasthenia gravis by oral administration of acetylcholine receptor. Wang, ZY., Qiao, J., Link, H.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of functionally distinct anti-C7 monoclonal antibodies and stratification of anti-nicotinic AChR positive Myasthenia Gravis patients. Lekova, E., Zelek, WM., Gower, D., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Approach to Reinstating Tolerance in Experimental Autoimmune Myasthenia Gravis Using a Targeted Fusion Protein, mCTA1-T146. Consonni, A., Sharma, S., Schön, K., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Baseline Decrement in Patients with Mild Myasthenia Gravis Predicts Immunomodulation Treatment. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Myasthenia Gravis. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

The best and worst of times in therapy development for myasthenia gravis. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Myasthenia gravis: subgroup classification and therapeutic strategies. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Pharmacological Management of Myasthenia Gravis: A Century of Expert Opinions in Cecil Textbook of Medicine. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Further developments with antisense treatment for myasthenia gravis. [2013]

7. Ireland pubmed.ncbi.nlm.nih.gov

Stimulated-single fiber electromyography monitoring of anti-sense induced changes in experimental autoimmune myasthenia gravis. [2007]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Suppression of experimental autoimmune myasthenia gravis by oral administration of acetylcholine receptor. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Discovery of functionally distinct anti-C7 monoclonal antibodies and stratification of anti-nicotinic AChR positive Myasthenia Gravis patients. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

A Novel Approach to Reinstating Tolerance in Experimental Autoimmune Myasthenia Gravis Using a Targeted Fusion Protein, mCTA1-T146. [2019]