Ofatumumab Dose-finding in Relapsing Remitting Multiple Sclerosis (RRMS) Patients (OMS115102)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00640328
First received: March 18, 2008
Last updated: June 19, 2014
Last verified: November 2012
  Purpose

The trial consists of a dose escalation, to establish the safety of ofatumumab in RRMS patients. A 48-week treatment period followed by an individualized follow-up period until normalization of peripheral B-cell counts or Immunoglobulin G (IgG) levels.


Condition Intervention Phase
Multiple Sclerosis
Drug: Ofatumumab 100
Drug: Ofatumumab 300
Drug: Ofatumumab 700
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Placebo Controlled, Multicenter, Dose-finding Trial of Ofatumumab in Relapsing Remitting Multiple Sclerosis (RRMS) Patients

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With Any Adverse Event [ Time Frame: First Treatment Period (FTP): From Visit 3 (Week 0) up to Visit 10 (Week 24); Second Treatment Period (STP): From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104) ] [ Designated as safety issue: No ]
    An Adverse Event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A list of all adverse events is reported in the "Other (Non-Serious) Adverse Events" section. Non-serious AEs were not collected during the Individualized Follow-up Period.

  • Number of Participants With the Indicated Critical Adverse Events (CAEs) [ Time Frame: FTP: From Visit 3 (Week 0) up to Visit 10 (Week 24); STP: From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104) ] [ Designated as safety issue: No ]
    A CAE=treatment-related (TR) grade (G) >=3 AE on day of infusion (inf.) preventing inf. to be resumed, a TR G 3 bronchospasm during 1 inf., an AE whose severity becomes G 3 for the third time during 1 inf., infections reported as serious, a TR neurological event consistent with progressive multifocal leukoencephalopathy (PML), any malignancy, and any fatal adverse drug reaction. AE severity (assessed as G 1-5) was classified using the Common Terminology Criteria for Adverse Events v3.0: G 1=mild AE; G 2=moderate AE; G 3=severe AE; G 4=life-threatening or disabling AE; G 5=death related to AE.

  • Number of Participants With Negative or Unconfirmed Human Anti-human Antibodies (HAHA) in Which Concentrations of Ofa Were Below 500 Nanograms Per Milliliter (ng/ml) [ Time Frame: Visit 3 (Week 0), Visit 10 (Week 24), Visit 17 (Week 48) or early withdrawal (EW), and Visit 26 (Week 104) ] [ Designated as safety issue: No ]
    Participants are checked for negative (or a lack of) HAHA at Baseline, and then throughout the study, to ensure that the investigational product is not causing HAHA development. Participants with concentrations of Ofa that are missing or are above 500 nanograms per milliliter (ng/mL) are considered to have unconfirmed HAHA results.

  • Number of Participants With Abnormal Physical Examination Findings [ Time Frame: FTP: From Visit 3 (Week 0) up to Visit 10 (Week 24); STP: From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104) ] [ Designated as safety issue: No ]
    The investigator performed the physical examination, which included but was not limited to: general appearance and the following body systems: lymph nodes, mouth and throat, lungs, cardiovascular, abdomen, extremities, muscular-skeletal, neurological (apart from multiple sclerosis [a brain and spinal cord disease]), and skin. All abnormal clinically relevant findings such as vein problems (venous varices), disorder of the vertebral column (vertebropathy), increased hearing loss, post operative mark (scar), and chronic skin disorder with no sweat and itching (anhidrotic eczema) were reported.

  • Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Basophils, Eosinophils, Leukocytes, Monocytes, Lymphocytes, Neutrophils, and Platelet Count at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP) [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: Visit 26 (Week 104) ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for hematology assessment. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in basophils, eosinophils, leukocytes, monocytes, lymphocytes, neutrophils, and platelets count was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Week 104 for the IFUP minus the value at Baseline.

  • Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Erythrocyte Count at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP) [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: Visit 26 (Week 104) ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for assessment of erythrocyte count. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in erythrocyte count was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.

  • Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Hematocrit at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP) [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: Visit 26 (Week 104) ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for hematocrit assessment. Hematocrit is the percentage of blood volume (BV) that is occupied by red blood cells (RBCs). Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in hematocrit was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline. Hematocrit is measured as a percentage, i.e., volume (V) of red blood cells per volume of blood.

  • Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Hemoglobin Count at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP) [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: Visit 26 (Week 104) ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for assessment of hemoglobin count. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in hemoglobin was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.

  • Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Albumin at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP) [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: VIsit 26 (Week 104) ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for assessment of albumin count. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 104 for the IFUP) in albumin was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.

  • Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Alkaline Phosphatase, Aspartate Aminotransferase (AST), and Alanine Transaminase (ALT) at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP) [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104) ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the assessment of alkaline phosphatase, AST, and ALT. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.

  • Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Bicarbonate, Glucose, Potassium, Sodium, and Urea at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP) [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104) ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the assessment of bicarbonate, glucose, potassium, and urea. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.

  • Change From Baseline (Week 0 for the FTP,Week 24 for the STP, and Week 0 for the IFUP) in Bilirubin and Creatinine at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP) [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104) ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the assessment of bilirubin and creatinine. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.

  • Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Immunoglobins at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP) [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104) ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for the assessment of antibodies produced by B-cells (immunoglobins): immunoglobulin A, immunoglobin G, and immunoglobin M. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.

  • Change From Baseline (Week 0 for the FTP and Week 24 for the STP) in Blood Pressure (BP) at Week 24 (FTP) and Week 48 (STP) [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48) ] [ Designated as safety issue: No ]
    Maximum (systolic) and minimum (diastolic) BP were assessed prior to infusion. Change from Baseline (Week 0 for the FTP and Week 24 for the STP) was calculated as the value at Visit 10 (Week 24) for the FTP and the value at Visit 17 (Week 48) for the STP minus the value at Baseline.

  • Change From Baseline (Week 0 for the FTP and Week 24 for the STP) in Pulse Rate at Week 24 (FTP) and Week 48 (STP) [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48) ] [ Designated as safety issue: No ]
    The pulse rate of each participant was assessed prior to infusion. Change from Baseline (Week 0 for the FTP and Week 24 for the STP) was calculated as the value at Visit 10 (Week 24) for the FTP and the value at Visit 17 (Week 48) for the STP minus the value at Baseline.

  • Change From Baseline (Week 0 for the FTP and Week 24 for the STP) in Temperature at Week 24 (FTP) and Week 48 (STP) [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48) ] [ Designated as safety issue: No ]
    The temperature of each participant was assessed prior to infusion. Change from Baseline (Week 0 for the FTP and Week 24 for the STP) was calculated as the value at Visit 10 (Week 24) for the FTP and the value at Visit 17 (Week 48) for the STP minus the value at Baseline.

  • Change From Baseline (Week 0 for the FTP and Week 24 for the STP) in Complement Activation (CH50) at Week 24 (FTP) and Week 48 (STP) [ Time Frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48) ] [ Designated as safety issue: No ]
    Blood samples of participants were collected for CH50 prior to and 2 hours after dosing, and the samples were sent to a Central Laboratory for analysis: Bio Analytical Research Corporation (BARC). Change from Baseline (Week 0 for the FTP; Week 24 for the STP) was calculated as the value at Weeks 24 (FTP) and 48 (STP) minus the value at Baseline. Ofa depletes (induces the cell death of) B cells. When Ofa binds to a B cell, it induces complement CH50, which in turn causes cell death via cytotoxicity. Therefore, the CH50 levels were measured to ensure that CH50 was being appropriately activated.


Secondary Outcome Measures:
  • Number of the Indicated Types of Lesions (Ls) Assessed Per Magnetic Resonance Imaging (MRI) [ Time Frame: FTP: From Visit 3 (Week 0) up to Visit 10 (Week 24); STP: From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104) ] [ Designated as safety issue: No ]
    The MRI scan was performed prior to dosing and could be performed up to 4 days prior to Visits 3 and 10. An IDMC reviewed the data. T1 enhancing Ls are enhanced by gadolinium, are considered representative of disease activity/inflammation, and may signify a relapse. Measurement of these Ls is comparative from visit to visit. "Total T1 enhancing Ls" represent the total of the new T1 enhancing Ls over the entire study period. T2 L measurements measure all Ls on the brain in terms of volume and size, measuring for new or enlarging Ls. T1 hypointensive Ls are areas of permanent damage.

  • Total Volume of T2 Lesions at Week 24 and Week 48 [ Time Frame: Visit 10 (Week 24) and Visit 17 (Week 48) ] [ Designated as safety issue: No ]
    The MRI scan should be performed prior to dosing and can be performed up to 4 days prior to Visits 3 and 10. An IDMC reviewed the data. The volume of T2 lesions was not a cumulative volume, but the volume measured at Visit 10 and Visit 17. T2 lesion measurements measure all lesions on the brain in terms of volume and size, measuring for new lesions or enlarging lesions.

  • Ofa Drug Concentration After the First (Visit 3), Second (Visit 4), Third (Visit 10), and Fourth (Visit 11) Intravenous (i.v.) Infusions [ Time Frame: Visit 3 (Week 0), Visit 4 (Week 2), Visit 10 (Week 24), and Visit 11 (Week 26). Samples were drawn predose, immediately following the end of infusion, 10 minutes after infusion, 1 hour after infusion, and 2 hours after infusion. ] [ Designated as safety issue: No ]
    The peripheral blood for each participant was collected and analyzed for the concentration of the drug in serum. There were four infusions in the study; the third infusion at Visit 10 represents the first infusion of the second treatment period (Weeks 24-48). Data are presented for the predose concentrations.

  • The Maximum Observed Plasma Concentration (Cmax) After the First (Visit 3), Second (Visit 4), Third (Visit 10), and Fourth (Visit 11) i.v. Infusions [ Time Frame: Visit 3 (Week 0), Visit 4, (Week 2), Visit 10 (Week 24), and Visit 11 (Week 26). Samples were drawn predose, immediately following the end of infusion, 10 minutes after infusion, 1 hour after infusion, and 2 hours after infusion. ] [ Designated as safety issue: No ]
    The peripheral blood for each participant was collected and analyzed for Cmax after the first, second, third, and fourth i.v. infusions. Assessment was performed using the noncompartmental method (this analysis is highly dependent on the estimation of total drug exposure).

  • The Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point (AUC(0-t)) After the First (Visit 3), Second (Visit 4), Third (Visit 10), and Fourth (Visit 11) i.v. Infusions [ Time Frame: Visit 3 (Week 0), Visit 4 (Week 2), Visit 10 (Week 24), and Visit 11 (Week 26). Samples were drawn predose, immediately following the end of infusion, 10 minutes after infusion, 1 hour (hr) after infusion, and 2 hours after infusion. ] [ Designated as safety issue: No ]
    The peripheral blood for each participant was collected and analyzed to estimate the area under the plasma concetration-time curve, AUC(0-t), and was assessed using the non-compartmental method.

  • Time to Reach Cmax (Tmax) After the First (Visit 3), Second (Visit 4), Third (Visit 10), and Fourth (Visit 11) i.v. Infusions [ Time Frame: Visit 3 (Week 0), Visit 4 (Week 2),Visit 10 (Week 24), and Visit 11 (Week 26). Samples were drawn predose, immediately following the end of infusion, 10 minutes after infusion, 1 hour after infusion, and 2 hours after infusion. ] [ Designated as safety issue: No ]
    The peripheral blood for each participant was collected and analyzed for tmax.

  • Clearance of Ofa Over the Course of Weeks 0-2 and 24-26 [ Time Frame: Weeks 0-2 and 24-26 ] [ Designated as safety issue: No ]
    The peripheral blood for each participant was collected and analyzed for clearance. Clearance is the measure of efficiency with which a drug is irreversibly removed form the body. The average clearance over the course of Weeks 0-2 and 24-26 is reported.

  • The Volume of Distribution at Steady State (Vss) of Ofatumumab Over the Course of Weeks 0-2 and 24-26 [ Time Frame: Weeks 0-2 and 24-26 ] [ Designated as safety issue: No ]
    The peripheral blood for each participant was collected and analyzed for Vss. The average Vss over the course of Weeks 0-2 and 24-26 is reported.

  • Half Life (t1/2) of Ofatumumab in the Terminal Elimination Phase Over the Course of Weeks 0-2 and 24-26 [ Time Frame: Weeks 0-2 and 24-26 ] [ Designated as safety issue: No ]
    The peripheral blood for each participant was collected and analyzed for half life. Half life is defined as the period of time required for the amount of drug in the body to be reduced by half. The average t1/2 over the course of Weeks 0-2 and 24-26 is reported.


Enrollment: 38
Study Start Date: May 2008
Study Completion Date: October 2011
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1.1
100mg ofatumumab then placebo
Drug: Ofatumumab 100
100mg
Drug: Placebo
matching placebo
Experimental: Cohort 1.2
placebo then 100mg ofatumumab
Drug: Ofatumumab 100
100mg
Drug: Placebo
matching placebo
Experimental: Cohort 2.1
300mg ofatumumab then placebo
Drug: Ofatumumab 300
300mg
Drug: Placebo
matching placebo
Experimental: Cohort 2.2
placebo then 300mg ofatumumab
Drug: Ofatumumab 300
300mg
Drug: Placebo
matching placebo
Experimental: Cohort 3.1
700mg ofatumumab then placebo
Drug: Ofatumumab 700
700mg
Drug: Placebo
matching placebo
Experimental: Cohort 3.2
placebo then 700mg ofatumumab
Drug: Ofatumumab 700
700mg
Drug: Placebo
matching placebo

Detailed Description:

The trial consists of two phases, a 48 week treatment period, followed by an individualized treatment period of up to two years.

Patients are treated in cohorts of increasing doses (100 mg, 300 mg and 700 mg) with 12 patients in each dose cohort. Within each cohort patients are randomized asymmetrically in a 2:1 ratio such that eight patients will receive ofatumumab and four patients will receive placebo. After 24 weeks the patients randomized to placebo will be treated with the active dose for the cohort. For blinding purposes, patients randomized to the active dose will be treated with placebo after 24 weeks. Thus, each patient will receive two administrations of trial product with 24 weeks follow-up resulting in a total treatment period of 48 weeks duration. An Independent Data Monitoring Committee (IDMC) will review and evaluate the safety data of each cohort, a minimum of 4 weeks data including the week 4 Magnetic Resonance Imaging (MRI) from at least 10 patients, to consider if progression to the next higher dose cohort is acceptable.

The trial product is administered as two infusions separated by two weeks. Clinical assessment and Gadolinium enhanced (Gd-enhanced) MRI scan will be performed at weeks -4, 0, 2, 4, and every 4 weeks until week 48. The MRI scan at week 2 is carried out for safety assessment prior to administering the second infusion in the first treatment course. When patients in all dose cohorts have been dosed and have had week 4 MRI scans performed, an IDMC will review all available safety data.

After completion of week 48 patients will be followed to monitor B-cell and IgG normalization. B-cell levels will be monitored every 12 weeks until CD19+ cells have returned to baseline level (Visit 3) or normalized level. If the B-cell levels are not normalized after two years the patient should be followed until either the IgG or the B-cell levels are normalized (see Section 9.2.4 for details). During this period Gd-enhanced MRI follow up scans will be performed every 12 weeks to evaluate potential rebound, safety and for Progressive Multifocal Leukoencephalopathy (PML) monitoring.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with definite diagnosis of relapsing-remitting MS according to McDonald criteria
  • Patients with:
  • At least two confirmed relapses within the last 24 months or
  • At least one confirmed relapse within the last 12 months or
  • One confirmed relapse between 12 and 24 months prior to screening, and at least one documented T1 Gd-enhancing lesion on an MRI performed within 12 months prior to screening.
  • Patients with disability equivalent to Expanded Disability Status Scale (EDSS) score of 0-5.0 (both included) at screening
  • Neurologically stable patients with no evidence of relapse for at least 30 days prior to start of Screening and during the Screening Phase
  • Female patients must be either post-menopausal, surgically incapable of bearing children or practicing an acceptable method of birth control e.g. hormonal contraceptives, intrauterine device, spermicide and barrier as long as they are on trial medication and for a period of 1 year following the last infusion of trial drug. Females of childbearing potential must have a negative pregnancy test at screening visit prior to entry into the treatment period
  • Following receipt of verbal and written information about the trial, the patient must provide signed informed consent before any trial related activity is carried out.

Exclusion Criteria:

  • Diagnosis of Secondary Progressive Multiple Sclerosis (SPMS), Primary Progressive Multiple Sclerosis (PPMS) or Progressive Relapsing Multiple Sclerosis (PRMS) or Neuromyelitis optica
  • Neurological findings consistent with Progressive Multifocal Leukoencephalopathy (PML) or confirmed PML
  • Findings on brain MRI scan indicating any other clinically significant brain abnormality other than MS
  • Patients unable to undergo MRI scans (e.g. due to pacemaker, severe claustrophobia, hypersensitivity to contrast media) or who lack adequate peripheral venous access
  • Patients who have had the following treatments:
  • Lymphocyte-depleting therapies (e.g. alemtuzumab (Campath®), anti-Cluster of Differentiation (CD4), cladribine, total body irradiation, bone marrow transplantation), mitoxantrone or cyclophosphamide at any time
  • Anti-CD20 treatments or any monoclonal antibodies at any time
  • Immunoglobulin, azathioprine, cyclosporine, tacrolimus or other immunosuppressive agents, immunomodulatory agents or plasma exchange within six months prior to randomization in the trial apart from Glatiramer Acetate and Interferon Beta (IFN-b).
  • Glatiramer Acetate or IFN-b within three months prior to the randomization in the trial.
  • Glucocorticoids or Adrenocorticotropic Hormone (ACTH) within one month prior to the screening in the trial.
  • Receipt of a live vaccine within one month prior to screening in the trial.
  • Plasmapheresis for treatment of relapses within 2 months prior to randomization in the trial.
  • Initiation of therapy with Statins or hormone replacement treatment within one month or less prior to screening in the trial.
  • Patients who have received other disease modifying therapies for MS may be allowed on a case to case basis after discussion with the sponsors medical monitor
  • Past or current history of medically significant adverse effects (including allergic reactions) from:
  • Cetirizine
  • Prednisolone
  • Paracetamol/acetaminophen
  • Plasma proteins or a known hypersensitivity to components of the investigational product.
  • Past or current malignancy, except for
  • Cervical carcinoma Stage 1B or less
  • Non-invasive basal cell and squamous cell skin carcinoma
  • Cancer diagnoses with a complete response of a duration of > 5 years. Patients with a prior history of hematological malignancies are excluded regardless of response
  • Clinically significant cardiac disease, including acute myocardial infarction within six months from screening, unstable angina, congestive heart failure, previous venous or arterial thrombosis or arrhythmia requiring therapy.
  • Electrocardiogram (ECG) showing significant abnormality that the treating investigator determines may jeopardize the subject's health (i.e. acute ischemia, left bundle branch or bifascicular block)
  • Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, immunodeficiency syndrome, pulmonary, cerebral, psychiatric or neurological disease which may impair their reliable participation in the trial or necessitate the use of medication not allowed by this protocol.
  • History of severe, clinically significant Central Nervous System (CNS) trauma (e.g. cerebral contusion, spinal cord compression) or a history or presence of myelopathy due to spinal cord compression by disk or vertebral disease
  • Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C. Any previous serious infections should be discussed with the sponsors medical monitor (e.g. opportunistic or atypical infections)
  • Female patients who are pregnant or nursing.
  • Use of an investigational drug or other experimental therapy for a condition other than MS within 4 weeks prior to screening. Any prior use of an investigational drug or other experimental therapy for MS at any time should be discussed with the medical monitor.
  • Current participation in any other interventional clinical trial. Participation in non-interventional trial requires approval of the protocol by the sponsor
  • Serum vitamin B12 below lower limit of normal
  • Positive polymerase chain reaction (PCR) screening for John Cunningham Virus (JC Virus) as measured by qualitative plasma and/or white blood cell JCV DNA
  • Serologic evidence of Hepatitis B (HB) infection based on the results of testing for Hepatitis B Surface Antigen (HBsAg), anti- Hepatitis B Core (HBc) and anti- Hepatitis B Surface (HBs) antibodies with eligibility based on the results as follows:
  • Patients positive for HBsAg are excluded
  • Patients negative for HBsAg but positive for both anti-HBc and anti-HBs antibodies (indicating past infection) are eligible
  • Patients negative for HBsAg and anti-HBc antibody but positive for anti-HBs antibody (indicating past vaccination) are eligible
  • Patients negative for HBsAg and anti-HBs antibody but positive for anti-HBc antibody will require clarification of their status by testing for HB DNA, which if positive will exclude the patient from participation
  • Patient with documented vaccination against Hepatitis B (primary and secondary immunization and booster) will be considered eligible for the trial.
  • Positive serology for HIV
  • Screening laboratory values:
  • White Blood Cell (WBC) < 3.0 x 109/L
  • Neutrophils < 2 x 109/L
  • Platelets < 100 x 109/L
  • Circulating IgG level < lower limit of normal (according to central laboratory range)
  • Serum Alanine Aminotransferase (S-ALAT) > 2.5 times the upper limit of normal (according to central laboratory range)
  • Serum Alpha Fetoprotein (S-AP) > 2.0 times the upper limit of normal (according to central laboratory range)
  • Serum Aspartate Aminotransferase (ASAT) >3.0 times the upper limit of normal (according to central laboratory range)
  • Bilirubin > 1.5 times the upper limit of normal (according to central laboratory range)
  • S-creatinine > the upper limit of normal (according to central laboratory range)
  • CD4 count <500 cells/mm3, CD4:CD8 <0.9
  • Patients known or suspected of not being able to comply with a trial protocol (e.g. due to alcoholism, drug dependency or psychological disorder).
  • Positive test for Hepatitis C antibody confirmed with a Hepatitis C real time (RT) PCR assay.

Patients who are positive for Hepatitis C antibody and negative when the Hepatitis C RT PCR assay is performed will be eligible for the study. Patients who are positive for Hepatitis C antibody and have a positive or indeterminate result when the Hepatitis C RT PCR assay is performed will not be eligible for the study.

  • Positive test results for tuberculosis using the QuantiFERON test and/or Chest X-ray findings suggestive of tuberculosis (TB). For patients who have had a Chest X-ray performed within the past 6 months without any findings indicative of TB, QuantiFERON test alone may be performed.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00640328

Locations
Czech Republic
MS centre of neurology clinic, Faculty policlinic
Praha 2, Praha, Czech Republic, 128 08
MS Centre of Neurology Department, Hospital Teplice
Teplice, Czech Republic, 415 29
Denmark
Danish Multiple Sclerosis Research Centre, Copenhagen University Hospital
Copenhagen, Denmark, 2100
Poland
Department of Neurology, Medical University of Lodz
Lodz, Poland, 91-153
Institute of Psychiatry and Neurology
Warszawa, Poland, 04-749
Serbia
Clinical Centre of Serbia, Institute of Neurology
Belgrade, Serbia, 11 000
Military Medical Academy, Clinic for Neurology
Belgrade, Serbia, 11 000
Clinical Centre Nis, Clinic for Neurology
Nis, Serbia, 18000
Sweden
Neuroimmunology Unit, Karolinska Hospital
Stockholm, Sweden, S-171 76
United Kingdom
The Waltn Centre for Neurology & Neurosurgery NHS Trust. Clinical Trials Unit
Fazakerley, Liverpool, United Kingdom, L97LJ
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00640328     History of Changes
Obsolete Identifiers: NCT01526993
Other Study ID Numbers: 115102, GEN414
Study First Received: March 18, 2008
Results First Received: November 1, 2012
Last Updated: June 19, 2014
Health Authority: Poland: Ethics Committees
United Kingdom: Research Ethics Committee
Denmark: The Danish National Committee on Biomedical Research Ethics
Denmark: Danish Dataprotection Agency
Sweden: Regional Ethical Review Board
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Czech Republic: Ethics Committee
Serbia: ALIMS - Medicines and Medical Devices Agency of Serbia
Poland: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Denmark: Danish Medicines Agency
Serbia: Ethics Committees
Sweden: Medical Products Agency
Czech Republic: State Institute for Drug Control

Keywords provided by GlaxoSmithKline:
relapsing forms of multiple sclerosis
ofatumumab
multiple sclerosis

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 26, 2014