The purpose of this study is to investigate the safety, PK parameters, PD responses, and clinical responses of multiple dose administration of MLN1202 in patients with relapsing remitting multiple sclerosis (RRMS).
Conditions
Interventions
Product Name: MLN1202
Product Code: MLN1202
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Not yet available
Current Sponsor code: Not yet available
Other descriptive name
Sponsors
Millennium Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each patient must meet all of the following inclusion criteria to be enrolled in the pre-treatment phase of the study: •Be 18 years of age or older •Have a diagnosis of RRMS •Have had at least 1 documented relapse of MS within 18 months prior to study entry •Have an Expanded Disability Status Score (EDSS) of 0 to 5.5, inclusive (see Study Manual for calculation details) •Be willing and able to comply with the protocol for the duration of the study period •Be willing to use adequate “double-barrier” contraceptive methods for the duration of the study period •If female, must be neither pregnant nor breast-feeding. Confirmation that the patient is not pregnant must be established by a negative serum hCG pregnancy test within 7 days of study entry and again within 7 days prior to the first administration of study drug. •Have given written informed consent prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care Each patient must meet the following inclusion criteria to be enrolled in the treatment phase of the study: •Have a total of at least 2 new Gd-enhancing lesions seen over the series of 3 pre-treatment MRIs. (Note: If a patient experiences a flare of disease during the pre-treatment period requiring the use of corticosteriods according to the exclusion criteria below, MRIs will not be performed for 2 months after completion of corticosteroids, at which time pre-screening monthly MRIs will then continue until the patient has completed 3 scans. The patient’s schedule of visits will be adjusted accordingly. The use of corticosteroids during the pre-treatment period will be limited to a 3 to 5 day course of IV methylprednisolone without subsequent oral corticosteroids.) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients meeting any of the following exclusion criteria are not to be enrolled in the study: •Have a diagnosis of PPMS or SPMS •Have received any investigational drug or experimental procedure within 3 months prior to Study Day 0 •If the patient has received disease-modifying cyclophosphamide (Cytoxan®) or mitoxantrone [Novantrone®] for MS, that treatment must have discontinued 6 months prior to study Day 0. •If the patient has received the following prior disease modifying treatments: (interferons [Avonex®, Rebif®, Betaseron®/Betaferem®], glatiramer acetate [Copaxone®], azathioprine [Imuran®]) for MS, that treatment must have discontinued at least 12 weeks prior to study Day 0. •If the patient has received disease-modifying methotrexate, IV immunoglobulin, cyclosporin, or plasma exchange for MS, that treatment must have discontinued at least 8 weeks prior to study Day 0. •If the patient has received prior treatment with corticosteroids for MS, the patient must have discontinued that treatment at least 8 weeks prior to Study Day 0. •If the patient has ever been exposed to Tysabri® (natalizumab) or any other VLA-4 (a4b1) antagonist. •Have an active infection or be considered to be at high risk for developing an infection, including reactivation of latent tuberculosis, in the opinion of the investigator. •Have a history of hepatitis B, C, or human immunodeficiency virus (HIV) •Have a chest X-ray within 6 months of Study Day 0 with clinically significant findings or abnormalities, in the opinion of the investigator •Have inadequate renal (serum creatinine >1.5 times the upper limit of normal [ULN]) or hepatic function (aspartate transaminase [AST] or alanine transaminase [ALT] >2 times the ULN) •Have a known history of cancer, except for distant history (>10 years) of carcinoma in situ of the cervix or adequately treated basal cell carcinoma of the skin •Received any live, attenuated vaccinations within 30 days prior to Study Day 0 •Have a history of illicit drug or alcohol abuse within 5 years of Study Day 0 •Have a history of hypersensitivity to prior mAb treatment •Have a history of allergy or sensitivity to Gd •Have a history that would preclude serial MRI scans (eg, known implanted devices, claustrophobia, chronic low back pain, involuntary movements, poor venous access)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of this study are to: •Determine the safety and tolerability of MLN1202 in patients with RRMS. •Determine the efficacy of MLN1202 in patients with RRMS by comparing the mean number of new gadolinium-diethylenetriamine pentaacetic acid(Gd)-enhancing lesions on magnetic resonance imaging (MRI) during the pretreatment phase with the mean number of new Gd enhancing lesions found during the treatment phase. ;Secondary Objective: The secondary objective of this study is to: •Characterize the pharmacokinetics (PK) and observe the pharmacodynamics (PD) responses in relation to MLN1202 in patients with RRMS •To observe other MRI assessments in relation to MLN1202 in patients with RRMS The exploratory objectives of this study are to: •Use mRNA or protein expression patterns of genes known to be involved in MS pathophysiology or chemokine pathways to further understand the mechanism of action of MLN1202 in patients with MS •Determine if select mRNA or protein expression patterns of genes known to be involved in MS pathophysiology or chemokine pathways are potentially useful biomarkers of clinical outcome to MLN1202 treatment of patients with MS ;Primary end point(s): •Safety: Safety will be assessed by vital sign measurement, physical examinations, MS relapses, changes in EDSS scores and standard laboratory test results, as well as the incidence of adverse events (AEs) and serious adverse events (SAEs). In addition, MRI scans will be monitored on a continuous basis throughout the study for any change from the pre-treatment phase. Immunogenicity will be assessed through monitoring human anti-human (anti-MLN1202) antibodies (HAHA). Delayed-type hypersensitivity (DTH) response to purified protein derivative (PPD)/tuberculin (TB) antigen will also be assessed. •Efficacy: The primary efficacy endpoint will be the comparison of the mean number of new Gd enhancing lesions on MRI during the pre-treatment phase with the mean number of new | — |
Countries
Czech Republic, Hungary, United Kingdom
Outcome results
None listed