E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing Remitting Multiple Sclerosis (RRMS) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063399 |
E.1.2 | Term | Relapsing-remitting multiple sclerosis |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Part A: Evaluate the safety of three doses of ofatumumab in patients with relapsing remitting multiple sclerosis (RRMS).
Part B: Determine the dose response of ofatumumab on disease activity based on MRI in patients with RRMS. |
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E.2.2 | Secondary objectives of the trial |
Part A: Evaluate the pharmacokinetic (PK) profile of ofatumumab in patients with RRMS.
Part B: - Determine the dose response of ofatumumab on clinical manifestations of MS. - Assess the safety and immunogenicity of ofatumumab in patients with RRMS. - Investigate the effect of re-dosing patients with ofatumumab. - Evaluate the PK profile of ofatumumab in patients with RRMS. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with definite diagnosis of relapsing-remitting MS according to McDonald criteria 2. Patients with: • At least two documented relapses within the last 24 months or • At least one documented relapse within the last 12 months or • One documented 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. 3. Patients with disability equivalent to Expanded Disability Status Scale (EDSS) score of 0-5.0 (both included) at screening 4. Neurologically stable patients with no evidence of relapse for at least 30 days prior to start of Screening and during the Screening Phase 5. Age 18-55 years 6. 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 7. 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. |
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E.4 | Principal exclusion criteria |
1. Diagnosis of SPMS, PPMS or PRMS or Neuromyelitis optica 2. Neurological findings consistent with PML or confirmed PML 3. Findings on brain MRI scan indicating any other clinically significant brain abnormality other than MS 4. Patients unable to undergo MRI scans (e.g. due to pacemaker, severe claustrophobia, hypersensitivity to contrast media) or who lack adequate peripheral venous access 5. Patients who have had the following treatments: • Lymphocyte-depleting therapies (e.g. alemtuzumab (Campath®), anti-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 IFN-Beta • Glatiramer Acetate or IFN-Beta within three months prior to the randomization in the trial • Glucocorticoids or 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 60 days 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 medical officer at Genmab A/S 6. 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 7. 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 8. 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 9. 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) 10. 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 11. History of severe, clinically significant 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 12. 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 Hep. C. Any previous serious infections should be discussed with the medical officer at Genmab A/S (e.g. opportunistic or atypical infections) 13. Female patients who are pregnant or nursing 14. 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 advisor. 15. Current participation in any other interventional clinical trial. Participation in non-interventional trial requires approval of the protocol by Genmab A/S 16. Vitamin B12 below the lower limit of normal with an abnormal methylmalonic acid level 17. Pos. PCR screening for JC Virus as measured by quantitative plasma JCV DNA 18. Pos. serology for Hep. B except for anti-HBs in patient with documented Hep. B vaccination 19. Pos. serology for HIV
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E.5 End points |
E.5.1 | Primary end point(s) |
Cumulative number of new Gd-enhancing lesions on T1-weighted MRI from week 8 to week 24. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 65 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit for individualized follow up |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |