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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Alemtuzumab GZ402673; Drug: Glatiramer acetate; Drug: Beta-Interferon; Drug: Methylprednisolone; Drug: Ranitidine; Drug: Ceterizine; Drug: Dexchlorpheniramine; Drug: Paracetamol; Drug: Acyclovir; Drug: Prednisolone; Drug: Diphenydramine; Drug: Other H1 antagonist; Drug: Other H1 antagonist

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1090
    • Investigational Site Number :0400001
• Belgium
  • Gent, Belgium, 9000
    • Investigational Site Number :0560001
• France
  • Le Kremlin Bicetre, France, 94270
    • Investigational Site Number :2500001
  • Strasbourg, France, 67091
    • Investigational Site Number :2500002
• Italy
  • Cagliari, Italy, 09126
    • Investigational Site Number :3800005
  • Milano, Italy, 20132
    • Investigational Site Number :3800001
  • Napoli, Italy, 80131
    • Investigational Site Number :3800004
• Netherlands
  • Rotterdam, Netherlands, 3015 CN
    • Investigational Site Number :5280001
• Poland
  • Warszawa, Poland, 04-730
    • Investigational Site Number :6160001
  • Lódzkie
    • Lodz, Lódzkie, Poland, 93-338
      • Investigational Site Number :6160003
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 60-355
      • Investigational Site Number :6160002
• Portugal
  • Coimbra, Portugal, 3000-075
    • Investigational Site Number :6200001
• Russian Federation
  • Moscow, Russian Federation, 119602
    • Investigational Site Number :6430001
  • Moscow, Russian Federation, 129110
    • Investigational Site Number :6430004
  • Saint-Petersburg, Russian Federation, 197022
    • Investigational Site Number :6430005
  • St-Petersburg, Russian Federation, 197110
    • Investigational Site Number :6430002
• Turkey
  • Ankara, Turkey, 06100
    • Investigational Site Number :7920002
  • Ankara, Turkey, 06500
    • Investigational Site Number :7920001
  • Istanbul, Turkey, 34390
    • Investigational Site Number :7920003
  • Istanbul, Turkey
    • Investigational Site Number :7920004
• United Kingdom
  • London, City Of
    • London, London, City Of, United Kingdom, WC1N 3JH
      • Investigational Site Number :8260002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Alemtuzumab; - 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. - Type: Experimental

Drug: Alemtuzumab GZ402673; Pharmaceutical form: solution, Route of administration: IV; Other Names: Lemtrada; Drug: Glatiramer acetate; Pharmaceutical form: solution, Route of administration: subcutaneous (SC); Other Names: Copaxone; Drug: Beta-Interferon; Pharmaceutical form: solution, Route of administration: SC / intramuscular (IM); Drug: Methylprednisolone; Pharmaceutical form: solution, Route of administration: IV; Drug: Ranitidine; Pharmaceutical form: tablet, Route of administration: oral; Drug: Ceterizine; Pharmaceutical form: tablet, Route of administration: oral; Drug: Dexchlorpheniramine; Pharmaceutical form: tablet, Route of administration: oral; Drug: Paracetamol; Pharmaceutical form: tablet, Route of administration: oral; Drug: Acyclovir; Pharmaceutical form: tablet, Route of administration: oral; Drug: Prednisolone; Pharmaceutical form: tablet, Route of administration: oral; Drug: Diphenydramine; Pharmaceutical form: solution, Route of administration: IV; Drug: Other H1 antagonist; Pharmaceutical form: solution, Route of administration: IV; Drug: Other H1 antagonist; Pharmaceutical form: tablet/pill, Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan	Number of new or enlarged T2 lesions per scan was defined as the total number of new or enlarged T2 lesion that occurred during a specified period divided by the total number of scans performed during that specified period.	Period 1: Month -4 up to Month 0, Period 2: Month 4 to Month 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Participants With New or Enlarged T2 Lesions Per MRI Scan	Number of participants with at least one new or enlarged T2 lesions per MRI scan was reported in this outcome measure. Number of new or enlarged T2 lesions per scan was defined as the total number of new or enlarged T2 lesion that occurred during treatment period divided by the total number of scans performed during treatment period.	Period 1: Month -4 up to Month 0, Period 2: Month 4 to Month 8
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Months 4 and 8	EDSS is an ordinal scale in half-point increments that qualifies disability in participants with MS. It consists of 8 ordinal rating scales assessing seven functional systems (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other). EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicated worst outcomes.	Baseline, Months 4 and 8
Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAE)	Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).	Up to 5 years
Annualized Relapse Rate (ARR)	Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).	Up to 5 years
Change From Baseline in Cognition Test Scores of Brief Visuospatial Memory Test - Revised (BVMT-R)	Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).	Up to 5 years
Change From Baseline in Cognition Test Scores of Symbol Digit Modality Test (SDMT)	Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).	Up to 5 years
Change From Baseline in Quality of Life (QoL) Measures of Pediatric Quality of Life (PedsQL) Questionnaire Score	Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).	Up to 5 years
Change From Baseline in Pediatric Quality of Life in Neurological Disorders (NeuroQoL) Questionnaire Score	Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).	Up to 5 years
Serum Concentrations of Alemtuzumab Over Time	Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).	Up to 5 years
Maximum Serum Concentration Observed (Cmax) of Alemtuzumab	Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).	Up to 5 years
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alemtuzumab	Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).	Up to 5 years
Area Under the Plasma Concentration-Time Curve (AUC) of Alemtuzumab	Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).	Up to 5 years
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Alemtuzumab	Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).	Up to 5 years
Terminal Half-life (T1/2z) of Alemtuzumab	Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).	Up to 5 years
Assessment of Lymphocyte Phenotyping	Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).	Up to 5 years
Percentage of Participants With Incidence of Antidrug Antibodies (ADA)	Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).	Up to 5 years

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2017
• Primary Completion (Actual): May 4, 2021
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 2, 2017
• First Submitted That Met QC Criteria: December 5, 2017
• First Posted (Actual): December 11, 2017

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Antineoplastic Agents, Immunological; Adjuvants, Immunologic; Anti-Ulcer Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Histamine H2 Antagonists; Prednisolone; Methylprednisolone; Interferons; Ranitidine; Interferon-beta; Alemtuzumab; Acyclovir; Glatiramer Acetate; (T,G)-A-L; Dexchlorpheniramine
• Other Study ID Numbers: EFC13429; 2016-003100-30 (EudraCT Number); U1111-1180-6352 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes