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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CNP-106 for individuals with myasthenia gravis, a condition that causes muscle weakness. The trial aims to determine the safety and effectiveness of CNP-106 and its behavior in the body. Participants will receive either CNP-106 or a placebo (a substance with no active medicine) to help researchers understand the treatment's potential benefits and side effects. This trial suits those with moderate to severe myasthenia gravis, significant muscle weakness, and positive tests for specific antibodies related to the condition. As a Phase 1, Phase 2 trial, it focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that CNP-106 is likely to be safe for humans?

Research has shown that CNP-106 has been studied for its safety and early effectiveness in treating myasthenia gravis, a condition where the immune system mistakenly attacks parts of the body. In earlier studies, patients generally tolerated CNP-106 well, and no major safety issues were reported, indicating that serious side effects were uncommon.

However, this remains early research. As a Phase 1b/2a trial, the primary goal is to assess how well people tolerate this treatment and to monitor for any side effects. This indicates that CNP-106 is in the early stages of human testing. The safety information from these trials is usually limited but crucial for understanding potential risks.

For those considering joining a trial, it's important to recognize that this research is a step toward understanding the safety of CNP-106. Always consult with a healthcare provider to fully understand what participating in the trial might entail. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Myasthenia Gravis?

Unlike existing treatments for myasthenia gravis, which typically include drugs like corticosteroids or acetylcholinesterase inhibitors, CNP-106 is an innovative therapy administered through an intravenous infusion. Researchers are excited about CNP-106 because it potentially offers a new mechanism of action by targeting specific pathways involved in the disease, which could lead to more effective management of symptoms. This approach might provide an alternative for patients who do not respond well to current medications, making it a promising development in the treatment landscape for myasthenia gravis.

What evidence suggests that CNP-106 might be an effective treatment for Myasthenia Gravis?

Research has shown that CNP-106, which participants in this trial may receive, targets specific parts of the acetylcholine receptor, crucial in Myasthenia Gravis. This treatment retrains the immune system to stop attacking these receptors, potentially slowing the disease. Studies with experimental models have demonstrated that this method can reduce symptoms. Early results suggest CNP-106 might effectively manage Myasthenia Gravis symptoms by addressing the root cause in the immune system. ^{1 2 3 4 5}

Who Is on the Research Team?

Roy First, MD

Principal Investigator

COUR Pharmaceutical

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11667273/

Antigen-specific immune therapy (CNP-106) for treatment of ... The aim of this study is to determine the safety and preliminary efficacy of CNP-106 in AChR antibody-positive generalised MG subjects.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39720510/

Antigen-specific immune therapy (CNP-106) for treatment ... The aim of this study is to determine the safety and preliminary efficacy of CNP-106 in AChR antibody-positive generalised MG subjects.

3. withpower.com withpower.com/trial/phase-2-myasthenia-gravis-2024-15158

CNP-106 for Myasthenia Gravis What data supports the effectiveness of the treatment CNP-106 for Myasthenia Gravis? Research shows that targeting specific parts of the acetylcholine receptor ...

4. researchgate.net researchgate.net/publication/387192351_Antigen-specific_immune_therapy_CNP-106_for_treatment_of_generalised_myasthenia_gravis_rationale_and_design_of_first-in-human_randomised_controlled_trial

(PDF) Antigen-specific immune therapy (CNP-106) for ... Data from experimental models suggest the potential benefit of CNP-106 to patients by reprogramming the immune system to AChR and stopping the progression of ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06106672

Study Details | NCT06106672 | Evaluate the Safety, ... 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.