CNP-106 for Myasthenia Gravis

Recruiting at 19 trial locations

Overseen By Harold Lee

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: COUR Pharmaceutical Development Company, Inc.

Must be taking: Corticosteroids, Pyridostigmine

Must not be taking: Tacrolimus, Methotrexate, Anti-FcRn, C5 inhibitors

Disqualifiers: Cerebrovascular accident, Thymic surgery, Tuberculosis, others

Compensation: Varies

Number of Visits: 2

Duration: 26 weeks

54 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are taking medications for myasthenia gravis, you must be on a stable dose for at least 90 days before joining the study and cannot increase the dose during the study unless approved by the medical team. Some specific medications, like Tacrolimus and Methotrexate, must be stopped well before the trial starts.

What data supports the effectiveness of the treatment CNP-106 for Myasthenia Gravis?

Research shows that targeting specific parts of the acetylcholine receptor (AChR) can reduce symptoms of myasthenia gravis in animal models. For example, using peptides or fragments of AChR has been effective in reducing disease severity and immune responses in experimental settings, suggesting potential for similar treatments like CNP-106. ^{1 2 3 4 5}

How is the treatment CNP-106 for myasthenia gravis different from other treatments?

CNP-106 is unique because it uses nanoparticle encapsulation to deliver acetylcholine receptor (AChR) epitopes, which may enhance the targeting and stimulation of immune cells more effectively than traditional methods. This approach could potentially offer a more precise way to modulate the immune response in myasthenia gravis. ^{2 3 4 5 6}

What is the purpose of this trial?

Phase 1b/2a First-in-Human (FIH) clinical trial to assess the safety, tolerability, pharmacodynamics (PD), and efficacy of multiple ascending doses of CNP-106.

Research Team

Roy First, MD

Principal Investigator

COUR Pharmaceutical

Eligibility Criteria

Adults aged 18-75 with Myasthenia Gravis (MG), experiencing muscle weakness, who have not had certain treatments or surgeries recently. They must have specific MG symptom scores, stable medication doses for 3 months, and agree to use effective birth control. Excludes those with mild or very severe MG, recent strokes, other immune disorders requiring immunosuppressants, significant cardiovascular disease, or a history of certain cancers.

Inclusion Criteria

I cannot become pregnant (e.g., due to surgery or menopause).

Subjects who are willing and able to provide Institutional Review Board (IRB) approved written informed consent and privacy language as per national regulations

You have a certain score from a test that shows you have a lot of non-eye symptoms from your condition.

Exclusion Criteria

My myasthenia gravis is either very mild or very severe.

I have had a stroke in the last year.

Your QMG score is less than 11 during screening.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 6 weeks

Treatment

Participants receive multiple ascending doses of CNP-106 or placebo via intravenous infusion on Day 1 and Day 8

26 weeks

2 visits (in-person) for infusions, additional visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CNP-106

Trial Overview The trial is testing CNP-106's safety and effectiveness in treating Myasthenia Gravis compared to a placebo. It's the first time this drug is being given to humans (First-in-Human) and will involve increasing doses to see how patients respond (multiple ascending doses).

Participant Groups

Group I: CNP-106 Experimental Treatment 1 Intervention

200 mL intravenous infusion on Day 1 and Day 8: CNP-106

Group II: Placebo Placebo Group 2 Interventions

CNP-106 Placebo

Who Is Running the Clinical Trial?

COUR Pharmaceutical Development Company, Inc.

Lead Sponsor

Trials

7

Recruited

250+

Findings from Research

Immunization with specific peptides from MHC class II molecules significantly reduced the occurrence and severity of experimental autoimmune myasthenia gravis (EAMG) in C57BL/6 mice, indicating a potential therapeutic approach for this condition.

The treatment not only improved clinical outcomes but also decreased antibody and T-cell responses against the target acetylcholine receptor (tAChR), suggesting that targeting disease-associated MHC could be an effective immunotherapy strategy for myasthenia gravis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccination with a MHC class II peptide in Alum and inactive pertussis strongly ameliorates clinical MG in C57BL/6 mice. Oshima, M., Maruta, T., Ohtani, M., et al.[2016]

Intranasal administration of recombinant fragments of the human nicotinic acetylcholine receptor (AcChoR) effectively prevents and suppresses experimental autoimmune myasthenia gravis (EAMG) in rats, indicating potential for therapeutic use in myasthenia gravis (MG).

The treatment led to significant immunological changes, including reduced T-cell responses, lower levels of anti-self AcChoR antibodies, and a shift in antibody isotypes, suggesting a broad immunomodulatory effect that could be beneficial for patients with MG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antigen-specific modulation of experimental myasthenia gravis: nasal tolerization with recombinant fragments of the human acetylcholine receptor alpha-subunit. Barchan, D., Souroujon, MC., Im, SH., et al.[2019]

Using immunomagnetic particles to present intact acetylcholine receptors (AChR) from muscle extracts significantly enhances the stimulation of T cells associated with myasthenia gravis (MG), making it at least 1,000 times more effective than soluble AChR.

This method of presenting AChR not only maximizes T cell activation but also suggests potential broader applications for studying other antigens, indicating a powerful tool for autoimmune research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stimulation of human T cells by sparse antigens captured on immunomagnetic particles. Hawke, S., Willcox, N., Harcourt, G., et al.[2019]

The study identified specific regions in the acetylcholine receptor (AChR) alpha-subunit that are crucial for inducing myasthenia in an animal model, highlighting the importance of conformational changes in B-cell and T-cell epitope recognition.

Model peptides synthesized from these regions were found to be immunogenic, leading to the production of antibodies that cross-react with the native AChR, suggesting that the antigenic conformation necessary for disease induction differs from that required for antibody reactivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myasthenogenicity in the main immunogenic region of acetylcholine receptor as modified by conformational design: an approach to antigenic synthetic peptides. Takamori, M., Hamada, T., Okumura, S.[2019]

The study identified specific peptides from the acetylcholine receptor alpha-subunit that can stimulate T cell proliferation in patients with myasthenia gravis (MG), indicating a potential mechanism for the disease's initiation and development.

Three out of eight tested peptides showed significant differences in their ability to provoke immune responses between myasthenic patients and healthy controls, suggesting that certain acetylcholine receptor epitopes are crucial in the pathogenesis of MG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro proliferative responses and antibody titers specific to human acetylcholine receptor synthetic peptides in patients with myasthenia gravis and relation to HLA class II genes. Brocke, S., Brautbar, C., Steinman, L., et al.[2018]

AChR-Fc, a novel fusion protein developed for myasthenia gravis (MG), effectively neutralizes autoantibodies against the nicotinic acetylcholine receptor, which are responsible for muscle weakness in MG patients.

In rat models of MG, AChR-Fc demonstrated a dose-dependent improvement in clinical symptoms, suggesting its potential as a new therapeutic option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Fusion Protein, AChR-Fc, Ameliorates Myasthenia Gravis by Neutralizing Antiacetylcholine Receptor Antibodies and Suppressing Acetylcholine Receptor-Reactive B Cells. Homma, M., Uzawa, A., Tanaka, H., et al.[2018]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Vaccination with a MHC class II peptide in Alum and inactive pertussis strongly ameliorates clinical MG in C57BL/6 mice. [2016]

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

Antigen-specific modulation of experimental myasthenia gravis: nasal tolerization with recombinant fragments of the human acetylcholine receptor alpha-subunit. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Stimulation of human T cells by sparse antigens captured on immunomagnetic particles. [2019]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Myasthenogenicity in the main immunogenic region of acetylcholine receptor as modified by conformational design: an approach to antigenic synthetic peptides. [2019]

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

In vitro proliferative responses and antibody titers specific to human acetylcholine receptor synthetic peptides in patients with myasthenia gravis and relation to HLA class II genes. [2018]

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

A Novel Fusion Protein, AChR-Fc, Ameliorates Myasthenia Gravis by Neutralizing Antiacetylcholine Receptor Antibodies and Suppressing Acetylcholine Receptor-Reactive B Cells. [2018]