Study of the Safety and Efficacy of MLN1202 in Patients in Multiple Sclerosis

A Phase 2a Magnetic Resonance Imaging Study of the Safety and Efficacy of MLN1202 in Patients in Multiple Sclerosis

This was a phase 2a study of MLN1202 to determine safety, tolerability and initial efficacy in patients with relapsing-remitting multiple sclerosis (RRMS). It was conducted in 2 dose cohorts enrolling a total of 50 patients. Efficacy was assessed by comparing the numbers of new gadolinium-enhancing brain lesions during the screening and treatment periods.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: MLN1202

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Each patient was to have met all of the following inclusion criteria to be enrolled in the study:

• 18 years of age or older
• Diagnosis of relapsing-remitting multiple sclerosis (RRMS)
• An Expanded Disability Status Score (EDCC) of 0 to 5.5, inclusive
• 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 or breast-feeding
• Written informed consent
• To be enrolled in the treatment phase of the study each patient must have a total of at least 2 new gadolinium-diethylenetriamine pentaacetic acid (Gd)-enhancing lesions seen over the series of 3 pretreatment magnetic resonance imaging (MRI)s.

Exclusion Criteria:

Patients meeting any of the following exclusion criteria were not to be enrolled in the study:

• Diagnosis of primary progressive multiple sclerosis (PPMS) or secondary progressive multiple sclerosis (SPMS)
• Received any investigational drug or experimental procedure within 3 months prior to study day 0

• If the patient has received disease-modifying treatments they must be discontinued prior to study day 0 as follows:

  1. Cyclophosphamide or mitoxantrone- 6 months prior
  2. Interferons, glatiramer acetate and azathioprine- 12 weeks prior
  3. Methotrexate, IV immunoglobulin, cyclosporin, plasma exchange or corticosteroids- 8 weeks prior
• Never have been exposed to Tysabri® (natalizumab)or any other VLA-4 (α4β1)antagonist
• Have an active infection or be considered to be at high risk for developing an infection
• 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
• Have inadequate renal or hepatic function
• 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 monoclonal antibody (mAb) treatment
• Have a history of allergy or sensitivity to Gd
• Have a history that would preclude serial MRI scans

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: SINGLE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MLN1202	Drug: MLN1202; Patients received 5 intravenous (IV) infusions of the study drug. The first 3 infusions were administered at 15-day intervals, followed by 2 infusions at 30-day intervals. Patients were randomized to receive 1 of 2 doses of MLN1202 (4mg/kg or 8mg/kg).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the safety and tolerability of MLN1202 in patients with relapsing-remitting multiple sclerosis (RRMS)	Vital sign measurement, physical examinations, multiple sclerosis (MS) relapses, changes in expanded disability status scale (EDSS) scores and standard laboratory test results, as well as the incidence of adverse events and serious adverse events	Day 61- Day 330
To determine the efficacy of MLN1202 in patients with RRMS	Comparing the mean number of new gadolinium-diethylenetriamine pentaacetic acid (Gd)-enhancing lesions on magnetic resonance imaging (MRI) scans during the pretreatment phase with the mean number of new Gd-enhancing lesions found during the treatment phase	Day 0- Day 180

Collaborators and Investigators

• Sponsor: Millennium Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (ACTUAL): July 1, 2007
• Study Completion (ACTUAL): October 1, 2007

Study Registration Dates

• First Submitted: September 9, 2010
• First Submitted That Met QC Criteria: September 9, 2010
• First Posted (ESTIMATE): September 13, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): September 13, 2010
• Last Update Submitted That Met QC Criteria: September 9, 2010
• Last Verified: September 1, 2010

More Information

Terms related to this study

• 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
• Other Study ID Numbers: MLN120204-063