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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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EUCTR |
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Last refreshed on:
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27 July 2020 |
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Main ID: |
EUCTR2004-002567-24-GB |
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Date of registration:
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22/02/2005 |
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Prospective Registration:
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Yes |
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Primary sponsor: |
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Public title:
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A Phase 2a Magnetic Resonance Study of the Safety and Efficacy of MLN1202 in Patients with Multiple Sclerosis - Not applicable
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Scientific title:
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A Phase 2a Magnetic Resonance Study of the Safety and Efficacy of MLN1202 in Patients with Multiple Sclerosis - Not applicable |
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Date of first enrolment:
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09/10/2006 |
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Target sample size:
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160 |
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Recruitment status: |
Not Recruiting |
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URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-002567-24 |
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Study type:
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Interventional clinical trial of medicinal product |
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Study design:
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Controlled: yes
Randomised: yes
Open: no
Single blind: no
Double blind: yes
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: no
Other: no
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): yes
Therapeutic confirmatory - (Phase III): no
Therapeutic use (Phase IV): no
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Countries of recruitment
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Czech Republic
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Hungary
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United Kingdom
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Key inclusion & exclusion criteria
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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 • 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.) of the study period
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:
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/®Betaferon®], 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)
Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
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Health Condition(s) or Problem(s) studied
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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).
MedDRA version: 8.1
Level: LLT
Classification code 10028245
Term: Multiple sclerosis
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Intervention(s)
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Product Name: MLN1202
Product Code: MLN1202
Pharmaceutical Form: Powder for solution for infusion
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Primary Outcome(s)
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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.
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Secondary Objective: Secondary objectives :
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
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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 Gd enhancing lesions found during the treatment phase as assessed by the central blinded MRI reader. Additional MRI assessments will include the T2-weighted lesion load, the volume of Gd-enhancing lesions, and volume of T1 weighted hypo-intense lesions.
•Pharmacokinetics: Initially, serum concentration-time data will be analysed using noncompartmental methods. Parameters such as maximum concentration (Cmax), clearance (CL), volume of distribution at steady state Vss, and half-life (t1/2) will be reported. Compartmental methods will be used to calculate maximum elimination rate (Vm), and Michaelis-Menten rate constant (Km), in addition to other PK parameters. Graphical methods will be used to relate these measures.
•Pharmacodynamics: The PD endpoints will be assessed by measuring free C-C chemokine receptor 2 (CCR2) receptors on CD14+ cells using a fluorescent-labelled antibody to CCR2 (free site assay) and by utilizing the fluorescent-labelled ligand, monocyte chemoattractant protein (MCP-1), to measure free CCR2 receptors on monocytes and memory CD4+ T cells (ligand internalization assay). PD measures will include percent positive cells (percentage of cells positive for the parameter being examined) and/or the molecule equivalence of soluble fluorochrome, often expressed and referred to as the mean equivalence of soluble fluorochrome (MESF).
•Exploratory Biomarkers: The exploratory biomarker endpoints will be assessed by correlating changes in protein or gene expression patterns at baseline and following MLN1202 treatment with changes in Gd-enhanced MRI brain lesions.
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Secondary ID(s)
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2004-002567-24-CZ
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Not applicable
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M120204-063
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Source(s) of Monetary Support
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Ethics review
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Status: Approved
Approval date: 09/10/2006
Contact:
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