A Study to Evaluate Efficacy, Safety, and Tolerability of Alemtuzumab in Pediatric Patients With RRMS With Disease Activity on Prior DMT

ID: NCT03368664
Status: Recruiting
Phase: Phase 3
Start Date: October 24, 2017
First Submitted: November 02, 2017
Last Updated: February 22, 2018
Results: N/A
Organization: Sanofi
Sponsors & Collaborators: Genzyme, a Sanofi Company
Location: Austria, Belgium, Czechia, France, Italy, Netherlands, Norway, Poland, Russian Federation, Spain, Turkey, United Kingdom
Conditions: Multiple Sclerosis
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Study Description

Brief Summary

Primary Objective:

To evaluate the efficacy, safety, and tolerability of alemtuzumab (IV) in pediatric patients from 10 to <18 years of age with Relapsing Remitting Multiple Sclerosis (RRMS) who have disease activity on prior Disease Modifying Therapy (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).

Detailed Description

The duration of study per patient will be approximately 5 years and 5 months.
Condition or disease Intervention/treatment Phase

Multiple Sclerosis

Drug: Alemtuzumab GZ402673
Other Names
Lemtrada
Drug: Glatiramer acetate
Other Names
Copaxone
Drug: Beta-Interferon
Other Names
Drug: Methylprednisolone
Other Names
Drug: Ranitidine
Other Names
Drug: Ceterizine
Other Names
Drug: Dexchlorpheniramine
Other Names
Drug: Paracetamol
Other Names
Drug: Acyclovir
Other Names
Drug: Prednisolone
Other Names
Phase 3

Tracking Information

First Submitted DateNovember 02, 2017
Last Update Posted DateFebruary 22, 2018
Actual Start DateOctober 24, 2017
Anticipated Completion DateMarch 01, 2025
Actual Primary Completion DateMarch 01, 2025
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Number of new or enlarging T2 lesions [Time Frame: month -4 to month 0 (Period 1) and month 4 to month 8 (Period 2)]

    The number of new or enlarging T2 lesions on brain MRI, during continuation of prior DMT (Period 1) compared to an equal period after the first course of alemtuzumab treatment (Period 2).

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Number of patients with new or enlarging T2 lesions [Time Frame: month -4 to month 0 (Period 1) and month 4 to month 8 (Period 2)]

    The proportion of patients with new or enlarging T2 lesions during continuation of prior DMT (Period 1) compared to an equal period after the first course of alemtuzumab treatment (Period 2)

  • Annualized relapse rate (ARR) [Time Frame: At Year 2]

    ARR at Year 2

  • Assessment of cognition test scores [Time Frame: Baseline to over 2 years]

    Change from baseline in cognition test scores of Brief Visuospatial Memory Test - Revised (BVMT-R) over 2 year

  • Assessment of cognition test scores [Time Frame: Baseline to over 2 years]

    Change from baseline in cognition test scores of Symbol Digit Modality Test (SDMT) over 2 years

  • Assesment of generic pediatric Quality of Life (QoL) measures [Time Frame: Baseline to over 2 years]

    Change from baseline in QoL measures of PedsQL questionnaire score over 2 years

  • Assesment of generic pediatric Quality of Life (QoL) measures [Time Frame: Baseline to over 2 years]

    Change from baseline in QoL measures of paediatric NeuroQoL questionnaire score over 2 years

  • Assessment of PK parameter: maximum concentration (Cmax) [Time Frame: 2 years]

    To evaluate maximum serum concentration observed

  • Assessment of PK parameter: time to Cmax (Tmax) [Time Frame: 2 years]

    To evaluate time to reach Cmax

  • Assessment of PK parameter: area under plasma concentration (AUC) [Time Frame: 2 years]

    7. To evaluate area under the cumulative serum concentration versus time curve

  • Assessment of PD parameter: lymphocyte phenotyping - 10 [Time Frame: until Month 60]

    Lymphocyte phenotyping will be assessed at screening until M24/at EOTP; annually in Safety Monitoring Phase

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleA Study to Evaluate Efficacy, Safety, and Tolerability of Alemtuzumab in Pediatric Patients With RRMS With Disease Activity on Prior DMT
Official TitleA Multi-center, Open-label, Single-arm, Before and After Switch Study to Evaluate the Efficacy, Safety and Tolerability of Alemtuzumab in Pediatric Patients With Relapsing Remitting Multiple Sclerosis (RRMS) With Disease Activity on Prior Disease Modifying Therapy (DMT)
Brief Summary

Primary Objective:

To evaluate the efficacy, safety, and tolerability of alemtuzumab (IV) in pediatric patients from 10 to <18 years of age with Relapsing Remitting Multiple Sclerosis (RRMS) who have disease activity on prior Disease Modifying Therapy (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).

Detailed Description

The duration of study per patient will be approximately 5 years and 5 months.

Study TypeInterventional
Study PhasePhase 3
Estimated Enrollment
50
Allocation
Not Available
Interventional Model
Single Group Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Multiple Sclerosis
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Alemtuzumab GZ402673

Pharmaceutical form:solution Route of administration: intravenous

Other Names
Lemtrada
Drug: Glatiramer acetate

Pharmaceutical form:solution Route of administration: subcutaneous

Other Names
Copaxone
Drug: Beta-Interferon

Pharmaceutical form:solution Route of administration: subcutaneous / intramuscular

Other Names
Drug: Methylprednisolone

Pharmaceutical form:solution Route of administration: intravenous

Other Names
Drug: Ranitidine

Pharmaceutical form:tablet Route of administration: oral

Other Names
Drug: Ceterizine

Pharmaceutical form:tablet Route of administration: oral

Other Names
Drug: Dexchlorpheniramine

Pharmaceutical form:tablet Route of administration: oral

Other Names
Drug: Paracetamol

Pharmaceutical form:tablet Route of administration: oral

Other Names
Drug: Acyclovir

Pharmaceutical form:tablet Route of administration: oral

Other Names
Drug: Prednisolone

Pharmaceutical form:tablet Route of administration: oral

Other Names
Study Groups/Cohorts
alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.

Study Arms
Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Alemtuzumab GZ402673
Pharmaceutical form:solution Route of administration: intravenous

Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Glatiramer acetate
Pharmaceutical form:solution Route of administration: subcutaneous

Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Beta-Interferon
Pharmaceutical form:solution Route of administration: subcutaneous / intramuscular

Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Methylprednisolone
Pharmaceutical form:solution Route of administration: intravenous

Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Ranitidine
Pharmaceutical form:tablet Route of administration: oral

Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Ceterizine
Pharmaceutical form:tablet Route of administration: oral

Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Dexchlorpheniramine
Pharmaceutical form:tablet Route of administration: oral

Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Paracetamol
Pharmaceutical form:tablet Route of administration: oral

Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Acyclovir
Pharmaceutical form:tablet Route of administration: oral

Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Prednisolone
Pharmaceutical form:tablet Route of administration: oral

Arm Intervention/Treatment
Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Alemtuzumab GZ402673
Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Glatiramer acetate
Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Beta-Interferon
Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Methylprednisolone
Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Ranitidine
Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Ceterizine
Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Dexchlorpheniramine
Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Paracetamol
Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Acyclovir
Experimental alemtuzumab
Dose 1 (initial course) of alemtuzumab will be administered intravenously on 5 consecutive days, followed by Dose 2 (second course) on 3 consecutive days administered 12 months after initial course. Pre-medications (methylprednisolone, prednisolone, H1 antagonist [antihistamine], H2 antagonist, paracetamol, acyclovir) will be administered prior alemtuzumab administration.
Drug : Prednisolone

Recruitment Information

Recruitment Status:Recruiting
Enrollment50
Completion DateMarch 01, 2025
Eligibility Criteria: Inclusion criteria :
- Patients with Relapsing Remitting Multiple Sclerosis (RRMS) aged from 10 years to less than 18 years at study entry are eligible. Patients should meet the criteria of diagnosis of Multiple Sclerosis as defined by the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for pediatric Multiple Sclerosis (MS) and the criteria of Multiple Sclerosis (MS) based on McDonald criteria 2010.
- Signed informed consent/assent obtained from patient and patient'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 Multiple Sclerosis (MS) attacks and at least 1 Multiple Sclerosis (MS) attack (relapse) in the last year during treatment with a interferon-beta (IFNB) or glatiramer acetate (GA) after having been on that therapy for at least 6 months
- 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 Multiple Sclerosis Disease Modifying Therapies (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.
- Patient 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 patient or any condition that could make the patient potentially non-compliant to the study procedures in the opinion of the Investigator.
- Mental condition rendering the patient 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 patient 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 patients or those who plan to become pregnant during the study.
- Unwilling to agree to use a reliable and effective contraceptive method as defined for contraception in the Informed Consent form (ICF) when receiving a course of alemtuzumab treatment and for 4 months following that course of treatment (fertile patients only).
- Female patients who have commenced menstruating (ie, 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 have residual immune suppression from these or other MS treatments.
- Treatment with teriflunomide in the last 12 months except if the patient 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 has not been approved at any dose or for any indication). Use of an investigational medication that was subsequently licensed and nonstandard use of a licensed medication (eg, using a dose other than the dose that is stated in the licensed product labeling or using a licensed therapy for an alternative indication) is not exclusionary. Prior treatment with herbal medications or nutritional supplements is 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.
- Patients 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 patient safety or interfere with the interpretation of study results, eg, current peptic ulcer disease, or other conditions that may 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 patient's ability to understand the patient 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 (eg, dysfibrinogenemia, factor IX deficiency, hemophilia, Von Willebrand's disease, disseminated intravascular coagulation [DIC], 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, patient is at high risk for infection (eg, 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 patient's potential participation in a clinical trial.
GenderAll
Age10 Years to 17 Years
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Austria
Belgium
Czechia
France
Italy
Netherlands
Norway
Poland
Russian Federation
Spain
Turkey
United Kingdom
Germany

Administrative Information

NCT Number:NCT03368664
Other Study ID Numbers
EFC13429
2016-003100-30
U1111-1180-6352
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Genzyme, a Sanofi Company
Collaborators
Not Available
Investigators
Study Director
Clinical Sciences & Operations
Sanofi