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 |
| Secondary identifying numbers | MBP8298-01 |
- 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
Scientific
501 Smyth Road
Ottawa
K1H 8L6
Canada
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | MBP8298 |
| Primary outcome measure | 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. |
| Secondary outcome measures | 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) |
| Overall study start date | 06/12/2004 |
| Completion date | 01/05/2008 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 65 Years |
| Sex | Both |
| Target number of participants | 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
- Canada
- Denmark
- Estonia
- Finland
- Germany
- Latvia
- Netherlands
- Spain
- Sweden
- United Kingdom
Study participating centre
501 Smyth Road
Ottawa
K1H 8L6
Canada
K1H 8L6
Canada
Sponsor information
BioMS Technology Corp (Canada)
Industry
Industry
6030 - 88 Street
Edmonton
T6E 6G4
Canada
| Phone | +1 780 413 7152 |
|---|---|
| tverco@biomsmedical.com | |
| Website | http://www.biomsmedical.com |
"ROR" |
https://ror.org/03fvjvp95 |
Funders
Funder type
Industry
BioMS Technology Corp (Canada)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | 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 |
