A Study to Evaluate Efficacy, Safety, and Tolerability of Alemtuzumab in Pediatric Patients With RRMS With Disease Activity on Prior DMT
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: Alemtuzumab GZ402673; Glatiramer acetate; Beta-Interferon; Methylprednisolone; Ranitidine; Ceterizine; Dexchlorpheniramine; Paracetamol; Acyclovir; Prednisolone; Diphenydramine; Other H1 antagonist; Other H1 antagonist
Intervention description: Pharmaceutical form: solution, Route of administration: IV; Pharmaceutical form: solution, Route of administration: subcutaneous (SC); Pharmaceutical form: solution, Route of administration: SC / intramuscular (IM); Pharmaceutical form: solution, Route of administration: IV; Pharmaceutical form: tablet, Route of administration: oral; Pharmaceutical form: tablet, Route of administration: oral; Pharmaceutical form: tablet, Route of administration: oral; Pharmaceutical form: tablet, Route of administration: oral; Pharmaceutical form: tablet, Route of administration: oral; Pharmaceutical form: tablet, Route of administration: oral; Pharmaceutical form: solution, Route of administration: IV; Pharmaceutical form: solution, Route of administration: IV; Pharmaceutical form: tablet/pill, Route of administration: oral
Intervention MeSH terms: Interferons; Acyclovir; Interferon-beta; Methylprednisolone; Prednisolone; Alemtuzumab; Glatiramer Acetate; Ranitidine; (T,G)-A-L; Dexchlorpheniramine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 10 Years
Maximum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To evaluate the efficacy, safety, and tolerability of alemtuzumab intravenously (IV) in
      pediatric participants from 10 to less than (<) 18 years of age with Relapsing Remitting
      Multiple Sclerosis (RRMS) who have disease activity on prior DMT.

      Secondary Objective:

      To assess the pharmacokinetics (PK), pharmacodynamics (PD), anti-drug antibody (ADA)
      formation, and potential effects of alemtuzumab on other multiple sclerosis (MS) disease
      characteristics such as cognition and quality of life (QoL).
    

Eligibility criteria:

        Inclusion criteria :

          -  Participants with RRMS aged from 10 years to <18 years at study entry are eligible.
             Participants must meet the criteria of diagnosis of MS as defined by the International
             Pediatric MS Study Group (IPMSSG) criteria for pediatric MS and the criteria of MS
             based on 2010 McDonald criteria.

          -  Signed written informed consent/assent obtained from participant and participant's
             legal representative (parent or guardian) according to local regulations.

          -  Expanded Disability Status Scale (EDSS) score of 0.0 to 5.0 (inclusive) at screening.

          -  At least 2 recorded MS attacks and at least 1 MS attack (relapse) in the last year
             during treatment with a beta interferon therapy (IFNB) or glatiramer acetate (GA)
             after being on that therapy for at least 6 months, and was currently still taking the
             same therapy.

          -  At least 1 of the following:

          -  >=1 new or enlarging T2 hyperintense lesion or gadolinium enhancing lesion while on
             that same prior therapy (IFNB or GA), or

          -  Two or more relapses in the prior year, or

          -  Tried at least 2 MS DMTs.

        Exclusion criteria:

          -  Any progressive or non-relapsing forms of MS.

          -  Conditions/situations such as:

          -  Impossibility to meet specific protocol requirements.

          -  Current participation in another interventional clinical study. Participants who are
             treated with a comparator agent approved for screening inclusion (INF or GA) may be
             considered for this trial.

          -  Participant is the Investigator or any Sub-Investigator, research assistant,
             pharmacist, study coordinator, other staff or relative thereof directly involved in
             the conduct of the protocol.

          -  Uncooperative participant or any condition that could make the participant potentially
             non-compliant to the study procedures in the opinion of the Investigator.

          -  Mental condition rendering the participant or parent/guardian unable to understand the
             nature, scope, and possible consequences of the study.

          -  Clinically relevant cardiovascular, hepatic, neurological, endocrine, or other major
             systemic disease making implementation of the protocol or interpretation of the study
             results difficult or that would put the participant at risk by participating in the
             study in the opinion of the Investigator.

          -  History of drug or alcohol abuse.

          -  History of known human immunodeficiency virus (HIV) positivity.

          -  Pregnant or breast-feeding female participants or those who had planned to become
             pregnant during the study.

          -  Unwilling to agree to use a highly effective contraceptive method when receiving a
             course of alemtuzumab treatment and for 4 months following that course of treatment
             (fertile participants only).

          -  Female participants who have commenced menstruating (i.e., are of childbearing
             potential) and are unwilling or unable to be tested for pregnancy.

          -  Previous treatment with alemtuzumab.

          -  Treatment with natalizumab, daclizumab, fingolimod, methotrexate, azathioprine,
             cyclosporine, or mycophenolate mofetil in the last 6 months prior to screening, or
             determined by the treating physician to had residual immune suppression from these or
             other MS treatments.

          -  Treatment with teriflunomide in the last 12 months except if the participant underwent
             the recommended elimination procedure as per Summary of Product Characteristics
             (SmPC).

          -  Previous treatment with mitoxantrone, cyclophosphamide, cladribine, rituximab,
             ocrelizumab, leflunomide, or any cytotoxic therapy.

          -  Previous treatment with any investigational medication (drug that had not been
             approved at any dose or for any indication). Use of an investigational medication that
             is subsequently licensed and nonstandard use of a licensed medication (e.g., using a
             dose other than the dose that is stated in the licensed product labeling or using a
             licensed therapy for an alternative indication) was not exclusionary. Prior treatment
             with herbal medications or nutritional supplements was also permitted.

          -  Intolerance of pulsed corticosteroids, especially a history of steroid psychosis.

          -  History of malignancy.

          -  Prior documented history of thrombocytopenia, or platelet count at screening < lower
             limits of normal (LLN).

          -  Any disability acquired from trauma or another illness that, in the opinion of the
             Investigator, could interfere with evaluation of disability due to MS.

          -  Participants with known Type 1 hypersensitivity or anaphylactic reactions to the
             active substances or any of the excipients, or intolerance of acyclovir or its
             therapeutic equivalent.

          -  Major systemic disease or other illness that would, in the opinion of the
             Investigator, compromise participant safety or interfere with the interpretation of
             study results, e.g., current peptic ulcer disease, or other conditions that might
             predispose to hemorrhage, immune cytopenias, rheumatoid arthritis, systemic lupus
             erythematosus, other connective tissue disorders, vasculitis, inflammatory bowel
             disease, severe psoriasis.

          -  Medical, psychiatric, cognitive, or other conditions that, in the Investigator's
             opinion, compromise the participant's ability to understand the participant
             information, to give informed consent, to comply with the trial protocol, or to
             complete the study.

          -  Major psychiatric disorder that is not adequately controlled by treatment in the
             opinion of the Investigator.

          -  Epileptic seizures that are not adequately controlled by treatment.

          -  Magnetic resonance imaging (MRI)-related conditions: conditions that could interfere
             with MRI acquisition and/or interpretation of MRI results (eg, claustrophobia,
             orthopedic implants/treatments, orthodontic treatments etc).

          -  Known bleeding disorder (e.g., dysfibrinogenemia, factor IX deficiency, hemophilia,
             Von Willebrand's disease, disseminated intravascular coagulation, fibrinogen
             deficiency, clotting factor deficiency).

          -  Prior history of invasive fungal infections.

          -  Active infection, eg, deep-tissue infection, that the Investigator considers
             sufficiently serious to preclude study participation.

          -  In the Investigator's opinion, participant is at high risk for infection (e.g.,
             indwelling catheter, dysphagia with aspiration, decubitus ulcer, history of prior
             aspiration pneumonia or recurrent urinary tract infection).

        The above information is not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.