Clinical trial NCT06106672: Evaluate the Safety, Tolerability, Pharmacodynamics and Efficacy of CNP-106 in Subjects With Myasthenia Gravis
Official title: A Phase 1b/2a Double Blind, Placebo Controlled Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Efficacy of CNP-106 in Subjects Ages 18-75 With Generalized Myasthenia Gravis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Myasthenia Gravis
Generalized Myasthenia
AChR Myasthenia Gravis
MuSK MG
Lead sponsor: COUR Pharmaceutical Development Company, Inc.
Sponsor class: INDUSTRY
First posted: 2023-10-30
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 the 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 III-IV (Cohort 1). Upon successful DMC review and approval of preliminary safety data obtained from Cohort 1 through Day 15, Cohort 2 will enroll subjects with MGFA Clinical Classification Class II-IV.
5. Subjects positive for anti-AChR antibodies by radioimmunoassay (RIA) (Mayo Clinic).

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 (ex. 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 through clinical 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 who have used the following medications:

   * Tacrolimus within 6 months prior to the first dosing;
   * Methotrexate within 5 half-lives or 90 days after last dose (whichever is longer);
   * Anti-FcRn inhibitors (ex. Efgartigimod) within 5 half-lives or 90 days after last dose (whichever is longer);
   * C5 complement inhibitor (ex. Eculizumab) within 5 half-lives or 90 days after last dose (whichever is longer);
   * Anti-CD20 (ex. Rituximab) within 5 half-lives for 90 days after last dose (whichever is longer);
   * Inclusion of subjects on 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 tuberculosis or positive PPD skin test.
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 as long as all inclusion and no other exclusion criteria are met.
13. Subjects with positive test results for hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen/antibody as determined at Screening.
14. Subjects with a history of or currently active immune disorders other than MG (including autoimmune disease) unless the condition, after discussion with the medical monitor and study site investigator, has been deemed to be acceptable for the subject's participation in this clinical study.
15. Subjects with a history of or current active diseases other than myasthenia gravis requiring immunosuppressive drugs (including azathioprine, prednisone, prednisolone, budesonide, cyclosporine, tacrolimus, methotrexate, or mycophenolate mofetil) unless the condition, after discussion with the medical monitor and site investigator, has been deemed to be acceptable for the subject's participation in this clinical study.
16. Subjects with a clinical history of significant cardiovascular disease as determined by the Investigator.
17. Subjects with a complication or medical history of malignancy within the past 5 years which, in the investigator's opinion, makes the subject unsuitable for study participation.
18. Subjects with a history of mast cell activation disease.
19. Subjects who, in the investigator's opinion, will be unable to adhere to study procedures.
20. Subjects who have received an investigational therapy other than CNP-106 within 28 days or 5 half-lives, whichever is longer, prior to Screening.
21. Subjects with any known active condition which, in the investigator's opinion, makes the subject unsuitable for study participation.
22. Known sensitivity to any components of CNP-106 (PLGA, sucrose, mannitol or sodium citrate).

Primary outcomes:
measure: Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs),
timeFrame: Through study day 180
Secondary outcomes:
measure: Change from baseline in antigen specific CD4+ and CD8+ T cell levels in PBMC at Day 60, 90, and 180.
timeFrame: Through study day 180
measure: Change from baseline in activated antigen specific CD4+ and CD8+ T cell levels in PBMC at Day 60, 90, and 180.
timeFrame: Through study day 180
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Phoenix
country: United States
facility: Neuromuscular Clinic and Research Center
state: Arizona
city: Brea
country: United States
facility: Infusion for Health
state: California
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Miami
country: United States
facility: Atlantis Research
state: Florida
city: Miami
country: United States
facility: Quantix Research, LLC
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: Insight Hospital and Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Dearborn
country: United States
facility: Insight Research Institute, Dearborn
state: Michigan
city: Columbia
country: United States
facility: University of Missouri, NextGen Precision Health
state: Missouri
city: Colombus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Nerve and Muscle Center of Texas
state: Texas
city: Houston
country: United States
facility: Prolato Clinical Research Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: COUR Pharmaceutical
name: Roy First, MD
role: STUDY_CHAIR
References: