ATX-MS-1467 in Patients With Relapsing Forms of Multiple Sclerosis

SAFETY AND PROOF OF PRINCIPLE STUDY OF ATX-MS-1467 IN PATIENTS WITH RELAPSING MULTIPLE SCLEROSIS: OPEN LABEL UPWARD TITRATION OVER FIVE DOSE LEVELS AND USING TWO ROUTES OF ADMINISTRATION (INTRADERMAL AND SUBCUTANEOUS).

Phase 1 study to assess the safety and biological activity of ATX-MS-1467 in patients with relapsing forms of multiple sclerosis. This will be an open label upward dose titration involving injections on 9 occasions, each two weeks apart. After dosing is complete there will be a 22 week follow up period. Blood samples will be drawn throughout the study to monitor safety and the body's response to the injections and MRI scans will be performed on several occasions to follow the course of the multiple sclerosis during the trial.

Study Overview

• Status: Completed
• Conditions: Relapsing Remitting Multiple Sclerosis
• Intervention / Treatment: Biological: ATX-MS-1467

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Chelyabinsk, Russian Federation, 454136
    • Municipal Healthcare Institution "City Clinical Hospital #3", Department of neurology
  • Kazan, Russian Federation, 420021
    • State Medical Institution "Republican Clinical Hospital of rehabilitation treatment of Ministry of Healthcare of Tatarstan Republic", Republican clinicodiagnostic center of demyelinating diseases of Ministry of Healthcare of Tatarstan Republic
  • Moscow, Russian Federation, 119991
    • State Educational Institution of Higher Professional Education "1st Moscow State Medical University n.a. I.M. Sechenov of Ministry of Healthcare and Social Development of the Russian Federation, Department of new drugs research
  • Rostov-on-Don, Russian Federation, 344015
    • State Healthcare Institution 'Rostov Regional Clinical Hospital' Center of Neurology
  • Saint Petersburg, Russian Federation, 191025
    • LLC "International Clinic MEDEM", Department of functional diagnostics
  • Saint Petersburg, Russian Federation, 197022
    • State Educational Institution of Higher Professional Education "St. Petersburg State Medical University n.a. I.V. Pavlov of Roszdrav", Department of neurology with clinic
  • Samara, Russian Federation, 443095
    • State Healthcare Institution "Samara Regional Clinical Hospital n.a. M.I. Kalinin", Department of neurosurgery
  • Saratov, Russian Federation, 410012
    • State Educational Institution of Higher Professional Education Saratov State Medical University
  • Smolensk, Russian Federation
    • State Educational Institution of Higher Professional Education "Smolensk State Medical Academy of Roszdrav", Department of neurology and neurosurgery based at State Healthcare Institution "Smolensk Regional Clinical Hospital"
  • St Petersburg, Russian Federation, 194354
    • St. Petersburg State Healthcare Institution "City multifield hospital #2", Department of neurology #2
  • St Petersburg, Russian Federation, 197376
    • Institution of the Russian Academy of Science "Institute of Human Brain of RAS", Neuroimmunology Laboratory
• United Kingdom
  • London, United Kingdom, WC1N 3BG
    • National Hospital for Neurology & Neurosurgery
  • Nottingham, United Kingdom, NG7 2UH
    • Queen's Medical Centre
  • Plymouth, United Kingdom, PL6 8BX
    • Peninsula Medical School
  • Sheffield, United Kingdom, S10 2 JF
    • Royal Hallamshire Hospital
  • Staffordshire
    • Stoke on Trent, Staffordshire, United Kingdom, ST4 7LN
      • North Staffordshire Royal Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Patients who have definite relapsing multiple sclerosis disease as defined by the McDonald criteria (McDonald et al., 2001 and 2005) and as assessed by a neurologist.

  2. HLA DRB1*15 positive.

  3. High baseline levels of T-cell proliferation in response to myelin basic protein, defined as >1000 cpm with a >3 stimulation index compared to background.

  4. Disease duration equal to or less than 10 years (from the first clinical event).

  5. At least one documented relapse in the previous 12 months or two relapses within the previous 24 months prior to screening.

  6. Must be in a clinically stable or improving neurological state during the 28 days preceding Screening.

  7. EDSS score < 5.5.

Exclusion Criteria:

• 1. Subjects treated with β-interferon, plasma exchange, intravenous gamma globulin within the 3 months prior to Study Day 1 2. Subjects treated with glatiramer acetate at any time in the past 3. Subjects who have been treated with parenteral steroids or adrenocorticotropic hormone within 3 months days prior to Study Day 1 4. Prior treatment with: cytotoxic agents (including but not limited to cladribine, mitoxantrone, cyclophosphamide, azathioprine, methotrexate), fingolimod, laquinimod, teriflunomide, total lymphoid irradiation, stem cell or bone marrow transplantation, or monoclonal antibody therapy (including natalizumab, daclizumab, alemtuzumab) 5. Prior use of disease related T-cell vaccine or peptide-tolerising agent to treat MS 6. Use of any investigational drug or experimental procedure within 6 months prior to Study Day 1 including cytokine or anti-cytokine therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intradermal injection; Injections will be given by the intradermal route	Biological: ATX-MS-1467; Disease specific immune modulating treatment for multiple sclerosis
EXPERIMENTAL: Subcutaneous injection; Injections will be given by the subcutaneous route	Biological: ATX-MS-1467; Disease specific immune modulating treatment for multiple sclerosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	Occurrence of treatment emergent Adverse Events (AE), Serious Adverse Events, and laboratory abnormalities up to week 48 compared to baseline.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Effect of ATX-MS-1467 on Brain Magnetic Resonance Imaging (MRI).	Number of new or persisting Gadolinium-enhancing lesions at week 16 and 20 when compared to baseline.	16 and 20 weeks

Collaborators and Investigators

• Sponsor: Apitope Technology (Bristol) Ltd.
• Collaborators: Aptiv Solutions; ClinStar, LLC
• Investigators: Principal Investigator: Jeremy Chataway, National Hospital for Neurology and Neurosurgery, London

Publications and helpful links

Helpful Links

• sponsor

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (ACTUAL): July 1, 2013
• Study Completion (ACTUAL): July 1, 2013

Study Registration Dates

• First Submitted: March 31, 2010
• First Submitted That Met QC Criteria: March 31, 2010
• First Posted (ESTIMATE): April 2, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): February 16, 2015
• Last Update Submitted That Met QC Criteria: February 3, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: Multiple sclerosis; Phase 1; Immunomodulation
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: ATX-MS-1467-002