AChR Myasthenia Gravis, Generalized Myasthenia, MuSK MG, Myasthenia Gravis
Conditions
Brief summary
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.
Detailed description
This is a 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. The clinical study lasts 222-days (up to 42 days for Screening, 180 Study Days). Subjects ages 18-75 with generalized myasthenia gravis (MG) will be screened up to 42 days prior to enrollment into the clinical study.
Interventions
DRUGCNP-106
CNP-106 is comprised of an antigenic AChR Peptide Pool (\~1 μg of each AChRα and AChRε peptide comprising AChR Peptide Pool Drug Substance per mg particles) dispersed within a negatively charged (-30 to -60 mV) polymer matrix of PLGA (Poly (DL-lactide-co-glycolide, 50:50 acid-end group)) particles (400-800 nm in size).
OTHERPlacebo
CNP-106 Placebo
Sponsors
COUR Pharmaceutical Development Company, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects who are willing and able to provide Institutional Review Board (IRB) approved written informed consent and privacy language as per national regulations. 2. Men and non-pregnant women, ages 18-75 years inclusive. 3. Female subjects of childbearing potential must agree not to become pregnant during the clinical study, have a negative pregnancy test at Screening Visit, and agree to one of the following: * Use two highly effective forms of birth control starting at initial screening and continuing throughout the study duration. * Practice abstinence starting at initial screening and continuing throughout the study duration. 4. Subjects with a Myasthenia Gravis Foundation of America Clinical Classification Class II-IV. 5. Subjects positive for anti-AChR antibodies by radioimmunoassay (RIA) (LabCorp Central Laboratory Services Inc.). 6. Subjects with MG-ADL Score ≥6 at Screening and Baseline Visit with ≥50% of the score derived from non-ocular symptoms. 7. Subjects with QMG Score ≥11 at Screening and Baseline Visit. 8. For subjects on any medication used to treat the symptoms of MG (e.g. Corticosteroids, pyridostigmine), subjects must be on a stable dose for a minimum of 90 days prior to enrollment and must agree not to increase their dose throughout the study duration unless reviewed and approved by the medical monitor and the site investigator. 9. Female subjects who agree to not breastfeed starting at initial screening and throughout the study duration. 10. Female subjects who agree to not donate ova starting at initial screening and throughout the study duration. 11. Male subjects with a spouse or partner of childbearing potential, who themselves and their spouse or partner agree to practice an effective form of birth control as discussed with the study doctor or study staff starting at Screening and throughout the study duration.
Exclusion criteria
1. Subjects with a Myasthenia Gravis Foundation of America Clinical Classification Class I or V. 2. Subjects with a history of cerebrovascular accident in the past 12 months. 3. Subjects with MG-ADL Score \<6 at Screen or Subjects with MG-ADL Score ≥6 at Screen with ˂50% of the score derived from non-ocular symptoms. 4. Subjects with QMG Score \<11 at Screen. 5. Subjects may enter the study following the washout periods for medications as described below prior to screening and refrain from usage throughout the study: * Tacrolimus within 6 months * Azathioprine, cyclosporine, methotrexate, or mycophenolate mofetil within 90 days * Anti-FcRn therapies: * Cyclic Anti-FcRns (e.g., efgartigimod alfa, rozanolixizumab) within 50 days * Chronic Anti-FcRns (e.g., nipocalimab) within 80 days; * C5 complement inhibitor (e.g., eculizumab) within 90 days * Anti-CD20 (e.g., rituximab) within 6 months; * Other immunomodulatory drugs will be at the discretion of the medical monitor and study site investigator. 6. Subjects who have used immunoglobulins given SC or IV (SCIg or IVIg) or plasmapheresis/plasma exchange (PE) within 4 weeks before Screening. 7. Subjects who have had thymectomy or any other thymic surgery performed within 12 months prior to Screening. 8. Subjects with untreated thymic malignancy, carcinoma, or thymoma. 9. Subjects with a history of untreated tuberculosis, a positive PPD skin test, or a positive QuantiFERON test. • Subjects with documented evidence of satisfactory TB treatment can be considered after review with the medical monitor and documentation of treatment course. 10. Subjects who have received administration of any live vaccine (other than intranasal Influenza) within 28 days or subunit vaccine within 14 days prior to Screening or are planning to receive any vaccination throughout the study duration. 11. Subjects who have received any COVID-19 vaccine within 14 days prior to Screening. Subjects who have received the first dose of any COVID-19 vaccine may not screen for the study until 14 days following their last dose of the vaccine if applicable. 12. Subjects with laboratory test results at Screening or prior to study dosing that are outside the normal limits and considered by the investigator to be clinically significant. Note: Clinically significant laboratory test results at screening that are related to the condition (MG) are acceptable if all inclusion and no other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs), | Through study day 180 | Frequency tables will be presented by treatment group for all AEs and SAEs by System Organ Class (SOC) and Preferred Term (PT). Frequency tables will also be produced by treatment group for AEs leading to COUR Pharmaceuticals Development Company, Inc. Confidential CNP-106-5.001 Protocol; IND 28774 Page 53 of 65 discontinuation from IP and study, by severity, and by causality. No formal statistical testing will be done. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in antigen specific CD4+ and CD8+ T cell levels in PBMC at Day 60, 90, and 180. | Through study day 180 | The mean change from Baseline to the endpoint within CNP-106 and Placebo treatment groups will be analyzed using ANOVA. |
| Change from baseline in activated antigen specific CD4+ and CD8+ T cell levels in PBMC at Day 60, 90, and 180. | Through study day 180 | The mean change from Baseline to the endpoint within CNP-106 and Placebo treatment groups will be analyzed using ANOVA. |
Countries
United States
Contacts
STUDY_CHAIRPaul Peloso, MD
COUR Pharmaceutical
Outcome results
None listed