A double-blind placebo-controlled multicenter study to evaluate the efficacy and safety of MBP8298 in subjects with secondary progressive multiple sclerosis (SPMS)

ISRCTN	ISRCTN98373474
DOI	https://doi.org/10.1186/ISRCTN98373474
Protocol serial number	MBP8298-01
Sponsor	BioMS Technology Corp (Canada)
Funder	BioMS Technology Corp (Canada)

Submission date: 13/06/2005
Registration date: 20/09/2005
Last edited: 01/07/2014

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Mark Freedman
Scientific

501 Smyth Road
Ottawa
K1H 8L6
Canada

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title
Study objectives	The major clinical hypothesis is that MBP8298 will significantly delay the progression of disability, as measured by the Expanded Disability Status Scale (EDSS), in subjects diagnosed with Secondary Progressive Multiple Sclerosis and who are human leukocyte antigen (HLA) DR2 and/or DR4 positive.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Secondary Progressive Multiple Sclerosis
Intervention	An intravenous administration of MBP peptide versus placebo
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	MBP8298
Primary outcome measure(s)	To compare the clinical efficacy of 500 mg MBP8298 given intravenously every 6 months for a period of 2 years, to placebo, in subjects diagnosed with SPMS who are positive for the HLA DR2 and/or DR4 haplotype. Clinical efficacy is defined as a statistically and clinically significant increase in the time to confirmed worsening of disability as measured by EDSS.
Key secondary outcome measure(s)	1. To assess safety of MBP8298 synthetic peptide in all subjects irrespective of genotype 2. To compare the clinical efficacy of 500 mg MBP8298 given intravenously every 6 months for a period of 2 years, to placebo, in subjects diagnosed with SPMS who are negative for the HLA DR2 and/or DR4 haplotype. Clinical efficacy is defined as a statistically and clinically significant increase in the time to confirmed worsening of disability as measured by EDSS. 3. To assess the effects of MBP8298 on MRI parameters: 3.1. Activity analysis (T2 lesions, Gadolinium-enhancing lesions) 3.2. Lesion burden (T2 burden of disease, chronic T1 black holes) 3.3. Atrophy (brain and cervical cord) 4. To confirm that treatment with MBP8298 induces immunological tolerance or shift in functional response profile to MBP peptide (82-98) and determine whether this is dependent on HLA subtype 5. To determine whether MBP8298 induces immunological tolerance or shift in functional response profile to other MBP epitopes and other myelin antigens (e.g., proteolipid protein [PLP], myelin oligodendrocyte glycoprotein [MOG]), indicating the stop of epitope spreading and whether this too is dependent on HLA subtype 6. To confirm the ratio of HLA DR2/4 positive to HLA DR2/4 negative subjects in the SPMS population 7. To determine whether MBP8298 induces an improvement in the quality of life of SPMS patients, as determined by the MSQoL-54 (SF-36 plus 18 MS-specific questions in Sweden and Norway)
Completion date	01/05/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	65 Years
Sex	All
Target sample size at registration	553
Key inclusion criteria	1. Male or female subjects, 18-65 years of age 2. Documented history of SPMS. SPMS is defined as an MS patient who has been diagnosed with MS for at least 3 years, and in the 3-year period prior to enrolment must have documented progression of their pyramidal or cerebellar Kurtzke functional subscores (FSS) in the absence of acute relapses. (In the absence of documented FSS changes, clinical notes documenting changes consistent with these changes will be acceptable). The subject must also have experienced at least one acute relapse as part of their diagnosis of Relapsing/Remitting Multiple Sclerosis (RRMS). Only one relapse prior to diagnosis of MS can be in accordance with the McDonald diagnostic criteria as long as cranial magnetic resonance imaging (MRI) findings consistent with the diagnosis of MS are also present. 3. Absence of relapse in the 3 months prior to baseline 4. EDSS of 3.5 6.5 5. Pyramidal or Cerebellar FSS ≥3 6. Subject must be able and willing to give meaningful, written informed consent prior to participation in the trial, in accordance with regulatory requirements 7. In the Investigators opinion, subjects must be reliable, compliant, and agree to cooperate with all trial evaluations
Key exclusion criteria	1. Diagnosis of Primary Progressive MS 2. Subjects have previously received MBP8298 3. Any known malignancy, or history of malignancy, with the exclusion of basal cell carcinoma 4. Steroid therapy within 30 days prior to first dose, or any other treatment known to be used for putative or experimental MS treatment 5. Therapy with ß-interferon, glatiramer acetate, mitoxantrone, cyclophosphamide, methotrexate, azathioprine, or any other immuno-modulating (e.g., intravenous immunoglobulin [IVIG]) or immunosuppressive drugs, including recombinant or non-recombinant cytokines or plasma exchange, within 6 months prior to performance of the first study-specific test, with the exception of corticosteroids or adrenocorticotropic hormone (ACTH) for relapse treatment. 6. Initiation of therapy with 4-aminopyridine (4-AP) or 3,4-diaminopyridine (3,4-DAP) 7. History of anaphylactic/anaphylactoid reactions to glatiramer acetate 8. Abnormal laboratory values at the Baseline Visit deemed by the Investigator to be clinically significant 9. Known allergy to Gadolinium-DTPA 10. Treatment at any time with Cladribine, total lymphoid irradiation, monoclonal antibody treatment e.g. anti-CD4, anti-CD52, anti-VLA4, anti-CD20 11. Treatment at any time with an altered peptide ligand 12. Any conditions that could interfere with the performance of study-specific procedures (e.g., MRI) 13. Previous randomization to this study 14. Known positivity for human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C 15. Participation in any other non-MS clinical trial within 30 days prior to performance of the first study-specific test (the screening/baseline visit), or any investigational therapy in the past 6 months 16. Females who are breastfeeding, pregnant (pregnancy test at screening), or not using a medically approved method of contraception regularly 17. Known or suspected current or past alcohol or drug abuse (within the last year) 18. Any medical, psychiatric or other condition that could result in a subject not being able to give fully informed consent, or to comply with the protocol requirements 19. Any other condition that, in the Investigators opinion, makes the subject unsuitable for participation in the study
Date of first enrolment	06/12/2004
Date of final enrolment	01/05/2008

Locations

Countries of recruitment

United Kingdom
Canada
Denmark
Estonia
Finland
Germany
Latvia
Netherlands
Spain
Sweden

Study participating centre

501 Smyth Road

Ottawa
K1H 8L6
Canada

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	18/10/2011		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes