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

NCT02609022 | Completed Phase 1 DMC

• 2 other identifiers: CV-00022015-002880-41
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Myasthenia Gravis

Keywords

Myasthenia Gravis; CV-MG01 therapeutic vaccine; Acetylcholine receptor mimetic peptides; Safety; Immunogenic response; First-in-Human; Proof-of-Concept; Myasterix

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Biomarker

  End of study part A (38 weeks)

• Clinical efficacy

  End of study part A (38 weeks)

Other Outcomes (1)

• Immune response

  End of study part A (38 weeks)

Study Arms (2)

CV-MG01

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Aluminium hydroxide adjuvant alone

Biological: Placebo

Interventions

CV-MG01 BIOLOGICAL

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.

CV-MG01

Placebo BIOLOGICAL

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• CuraVac: lead
• Aepodia: collaborator
• University Hospital, Antwerp: collaborator
• Leiden University Medical Center: collaborator

Study Sites (1)

University Hospital, Antwerp

Edegem, Antwerp, 2650, Belgium

Location

Related Publications (2)

• Weathington NM, Blalock JE. Rational design of peptide vaccines for autoimmune disease: harnessing molecular recognition to fix a broken network. Expert Rev Vaccines. 2003 Feb;2(1):61-73. doi: 10.1586/14760584.2.1.61.

  PMID: 12901598 BACKGROUND

• Galin FS, Chrisman CL, Cook JR Jr, Xu L, Jackson PL, Noerager BD, Weathington NM, Blalock JE. Possible therapeutic vaccines for canine myasthenia gravis: implications for the human disease and associated fatigue. Brain Behav Immun. 2007 Mar;21(3):323-31. doi: 10.1016/j.bbi.2006.10.001. Epub 2006 Nov 20.

  PMID: 17113748 BACKGROUND

Related Links

• CuraVac: Therapeutic Vaccines for Autoimmune Diseases

MeSH Terms

Conditions

Myasthenia Gravis

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Rudy Mercelis, MD, PhD

  University Hospital, Antwerp

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2015
• First Posted: November 20, 2015
• Study Start: March 1, 2016
• Primary Completion: September 30, 2018
• Study Completion: September 30, 2018
• Last Updated: January 28, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)