E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing Remitting Multiple Sclerosis |
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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 | LLT |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective of study CAMMS323 is to compare the safety and efficacy of 2 annual cycles of IV alemtuzumab to 3-times weekly SC administration of interferon beta-1a.
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of the CAMMS323 trial are: - Proportion of patients who are relapse free at Year 2 - Change from baseline in EDSS - Acquisition of disability as measured by change from baseline in MSFC - Percent change from baseline in MRI-T2-hyperintense lesion volume at Year 2 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Four sub-studies are included in this protocol (same protocol version number and date) which will be conducted at selected centres on a subpopulation of patients: - Laboratory substudy. Additional testing for the following parameters: expanded hematology, expanded thyroid function monitoring - Semen substudy. Semen analysis of sperm count and motility. If agglutination is present, subsequent testing for anti-sperm antibodies. - Expanded imaging substudy. Additional MTR (to measure abnormalities in normal-appearing white matter, which may be indicative of demyelination assciated with the effects of MS) and/or MRS (thought to be a marker for axonal preservation and thus a useful counterpoint to MTR measurement of demyelination) and/or DWI (measuring diffusion of water in tissues, which can be adapted to reveal the state of white matter including demyelinating MS lesions) - Pharmacokinetic substudy. PK samples drawn in two sub-cohorts (dense or sparse collection) |
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E.3 | Principal inclusion criteria |
• Signed informed consent form (ICF) • Age 18 to 50 years old (inclusive) as of the date the ICF is signed • Diagnosis of MS per update of McDonald criteria, and cranial MRI scan demonstrating white matter lesions attributable to MS within 5 years of Screening • Onset of MS symptoms (as determined by a neurologist, either at present or retrospectively) within 5 years of the date the ICF is signed • EDSS score of 0.0 to 3.0 (inclusive) at Screening • >/= 2 MS attacks (first episode or relapse) occurring in the 24 months prior to the date the ICF is signed, with >/= 1 attack in the 12 months prior to the date the ICF is signed, with objective neurological signs confirmed by a physician, nurse practitioner, or other Genzyme-approved health-care provider. The objective signs may be identified retrospectively.
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E.4 | Principal exclusion criteria |
• Current participation in another clinical study • Received prior therapy for MS other than corticosteroids, eg, alemtuzumab, interferons, IV immunoglobulin, glatiramer acetate, natalizumab, and mitoxantrone • Exposure to azathioprine, cladribine, cyclophosphamide, cyclosporine A, methotrexate, or any other immunosuppressive agent other than systemic corticosteroid treatment • Received treatment with a monoclonal antibody for any reason • Previous treatment with any investigational medication, ie drug has not been approved at any dose or for any indication (Prior treatment with herbal medications or nutritional supplements is permitted.) • Has any progressive form of MS • History of malignancy (except basal skin cell carcinoma) • Any disability acquired from trauma or another illness that, in the opinion of the Investigator, could interfere with evaluation of disability due to MS • Previous hypersensitivity reaction to any immunoglobulin product • Known allergy or intolerance to interferon beta, human albumin, or mannitol • Intolerance of pulsed corticosteroids, especially a history of steroid psychosis • Inability to self-administer SC injections or receive SC injections from caregiver • Inability to undergo MRI with gadolinium administration • CD4+, CD8+ B-cell count, absolute neutrophil count < LLN at Screening (see protocol) • Absolute neutrophil count <LLN at Screening • Known bleeding disorder (eg, dysfibrinogenemia, factor IX deficiency, hemophilia, Von Willebrand’s disease, disseminated intravascular coagulation (DIC), fibrinogen deficiency, or clotting factor deficiency) • Seropositivity for human immunodeficiency virus (HIV) • Significant autoimmune disease including but not limited to immune cytopenias, rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders, vasculitis, inflammatory bowel disease, severe psoriasis • Presence of anti-thyroid stimulating hormone (TSH) receptor (TSHR) antibodies (ie, above the LLN)• Active infection, eg, deep-tissue infection, that the Investigator considers sufficiently serious to preclude study participation • In the Investigator’s opinion, is at high risk for infection (eg, indwelling catheter, dysphagia with aspiration, decubitus ulcer, history of prior aspiration pneumonia or recurrent urinary tract infection) • Latent tuberculosis unless effective anti-tuberculosis therapy has been completed, or active tuberculosis. More specific guidance on tuberculosis testing and patient eligibility is provided in the Study Operations Manual (SOM) • Infection with hepatitis C virus • Past or present hepatitis B infection (positive hepatitis B serology) • Of childbearing potential with a positive serum pregnancy test, pregnant, or lactating • Unwilling to agree to use a reliable and acceptable contraceptive method throughout the study period (fertile patients only). Reliable and effective contraceptive method(s) include: intrauterine device (IUD), hormonal-based contraception, surgical sterilization, abstinence, or double-barrier contraception (condom and occlusive cap [diaphragm or cervical cap with spermicide]) • Major psychiatric disorder that is not adequately controlled by treatment • Epileptic seizures that are not adequately controlled by treatment • Major systemic disease or other illness that would, in the opinion of the Investigator, compromise patient safety or interfere with the interpretation of study results, eg, current peptic ulcer disease or other conditions that may predispose to hemorrhage • Medical, psychiatric, cognitive, or other conditions that, in the Investigator’s opinion, compromise the patient’s ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study • Confirmed platelet count </= the lower limit of normal (LLN) of the evaluating laboratory at Screening or documented at <100,000 µL within the past year on a sample without platelet clumping • Prior history of invasive fungal infections • Cervical high risk human papillomavirus (HPV) positivity or abnormal cervical cytology other than abnormal squalors cells of undetermined significance (ASCUS) • Seropositive for Trypanosoma cruzi or the Human T-lymphotropic virus type I or type II (HTLV-I/II) (testing required in endemic regions only). Guidance on region-specific testing recommendations and patient eligibility is provided in the SOM • Any other illness or infection (latent or active) that, in the Investigator’s opinion, could be exacerbated by either study medication • Any hepatic or renal function value grade 2 or higher at Screening, with the exception of hyperbilirubinemia due to Gilbert’s syndrome (see protocol)
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E.5 End points |
E.5.1 | Primary end point(s) |
The study will be considered to have met its primary efficacy objectives if a statistically significant difference between alemtuzumab and sc interferon-beta-1a groups observed for time to SAD or relapse rate |
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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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 61 |
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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End of trial = For each patient 2 years after initiation of treatment at Month 0, therefore end of trial will be 2 years after initiation of treatment at Month 0 of the last patient. As alemtuzumab-treated patients must be followed for safety for at least 4 years from their last cycle of treatment at Month 12, following study completion, all alemtuzumab-treated patients will be enrolled in an extension study that will include safety monitoring |
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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 | 3 |
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 | 3 |