Safety, Tolerability and Immunogenic Response of CV-MG01 in Patients With Myasthenia Gravis

Study Overview
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Brief Summary
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Study CV-0002 is the first clinical trial administering CV-MG01 in humans. This clinical trial is a safety and proof-of-concept study (proof of mechanism of action) intended to assess the safety, tolerability and immunogenic response following 3 subcutaneous injections of CV-MG01 as a potential therapeutic vaccine / active immunotherapy in myasthenia gravis (MG) patients.

Detailed Description
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Part A of the trial has been designed as a human safety pharmacology and therapeutic exploratory, parallel group, randomised, placebo-controlled, single centre, Investigator and subject-blind study using adaptive dose and sample size approaches. At the end of part A of the present study, all patients, including those receiving placebo, will be monitored in an open label, long-term safety follow-up part B of the study to assess the treatment effects over time.

Official Title
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A First-in-human and Proof-of-concept Study to Assess the Safety, Tolerability and Immunogenic Response of CV-MG01, Acetylcholine Receptor Mimetic Peptides, as Potential Therapeutic Vaccine, in Patients With Myasthenia Gravis

Conditions
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Myasthenia Gravis

Intervention / Treatment
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* Biological: CV-MG01
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects, with ocular and generalised myasthenia gravis (grade 1-2-3). Between the ages of 18 and 64 years, inclusive, at the time of the first injection. A Body Mass Index (BMI) between 18 and 35 kg/m2, inclusive. Patient with positive antibodies to AChR based on radioimmunoassay(RIA) (AChRAb ≥ 1 nmol/l); if available, historical data on AChR Ab levels over the last 2 years will be collected in the study records. Patient may use corticosteroid treatment, equivalent to a daily dose of 30 mg prednisone or lower and stable (dose +/- 5 mg) during the 3 months before participation. Patient may use one immunosuppressive drug with or without concomitant use of corticosteroid, providing that the dosage has been stable/unchanged for 3 months before participation. Blood pressure and heart rate (supine & standing) within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator. Venous access sufficient to allow blood sampling as per the protocol. Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures. Have given written informed consent approved by the relevant Ethics Committee (EC) governing the site. Exclusion Criteria: MG patients of Grade 4 or 5 based on myasthenia gravis foundation of America (MGFA) classification. Patients with history or presence of a primary or recurrent malignant disease including the presence or history of a thymoma. Thymectomy planned during part A of the study period or performed within 1 year prior to the first dose of study vaccine. Any confirmed or suspected immunosuppressive or immunodeficient condition not related to the treatment of MG, including human immunodeficiency virus (HIV) infection, or a family history of congenital or hereditary immunodeficiency. History or evidence of administration of immunoglobulins and/or any blood products within 3 months prior to the first dose of study vaccine or a planned administration of immunoglobulins during the first 3 months of the trial. History or evidence of rituximab treatment within 6 months prior to first dose of study vaccine. History or evidence of plasmapheresis within 3 months prior to the first dose of study vaccine or a planned plasmapheresis during the first 3 months of the trial. At high risk for aspiration. Pulmonary: forced vital capacity reduced to less than 70% of predicted capacity. History of severe allergic disease or reactions likely to be exacerbated by any component of the vaccine. History or evidence of Lambert-Eaton myasthenic syndrome, drug-induced myasthenia gravis, hereditary forms of myasthenic syndrome. History of relevant chronic degenerative, psychiatric, or neurological disorder other than MG. Severe hepatic, renal or cardiac insufficiency. Major congenital defects or serious chronic illness other than MG. Positive pregnancy test or desire to become pregnant during the study. Female patients of child-bearing potential that do not use a reliable and highly effective method of contraception at least one month before first injection, during the study and until 3 months after the last injection. Any significant out-of-range Clinical Laboratory results considered as clinically significant according to Investigator's judgment. Previous completion or withdrawal from this study. Sponsor employees or investigator site personnel directly affiliated with this study, and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted. Any medical condition that, in the opinion of the Investigator, might interfere with the subject's participation in the study, poses any added risk for the subject, or confounds the assessment of the subjects.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CV-MG01<br>The therapeutic vaccine candidate, CV-MG01 comprises two short synthetic peptides separately conjugated to a carrier protein for the potential treatment of myasthenia gravis | Biological: CV-MG01<br>* 3 consecutive subcutaneous injections of CV-MG01. The three injections are planned for each patient on Days 1, 29 (+/- 3 days) and 85 (+/- 7 days), respectively. Two dose levels: low and high dose.<br>|
| Placebo Comparator: Placebo<br>Aluminium hydroxide adjuvant alone | Biological: Placebo<br>* 3 consecutive subcutaneous injections of placebo. The three injections are planned for each patient on Days 1, 29 (+/- 3 days) and 85 (+/- 7 days), respectively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Safety assessed by laboratory tests, vital signs, electrocardiogram (ECG), adverse events, assessment of local tolerance, physical exams | End of study part A (38 weeks) | 
| Immunogenicity | To assess the immunogenic response after subcutaneous injections of CV-MG01 on the plasma levels of anti-peptide antibodies. | End of study part A (38 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker | To assess the effect of CV-MG01 subcutaneous injections on the plasma level of acetylcholine receptor antibodies. | End of study part A (38 weeks) | 
| Clinical efficacy | Clinical efficacy assessed by Quantitative MG testing Procedure extended with MG Composite Scale and MG-ADL (myasthenia gravis activities of daily living) | End of study part A (38 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myasthenia Gravis, CV-MG01 therapeutic vaccine, Acetylcholine receptor mimetic peptides, Safety, Immunogenic response, First-in-Human, Proof-of-Concept, Myasterix