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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03368664
Recruitment Status : Active, not recruiting
First Posted : December 11, 2017
Results First Posted : July 12, 2022
Last Update Posted : July 12, 2022
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Brief 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).


Condition or disease Intervention/treatment Phase
Multiple Sclerosis 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 Phase 3

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : October 24, 2017
Actual Primary Completion Date : May 4, 2021
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Alemtuzumab

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 Name: Lemtrada

Drug: Glatiramer acetate
Pharmaceutical form: solution, Route of administration: subcutaneous (SC)
Other Name: 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




Primary Outcome Measures :
  1. Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan [ Time Frame: Period 1: Month -4 up to Month 0, Period 2: Month 4 to Month 8 ]
    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.


Secondary Outcome Measures :
  1. Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Participants With New or Enlarged T2 Lesions Per MRI Scan [ Time Frame: Period 1: Month -4 up to Month 0, Period 2: Month 4 to Month 8 ]
    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.

  2. Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Months 4 and 8 [ Time Frame: Baseline, 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.

  3. Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAE) [ Time Frame: Up to 5 years ]
    Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).

  4. Annualized Relapse Rate (ARR) [ Time Frame: Up to 5 years ]
    Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).

  5. Change From Baseline in Cognition Test Scores of Brief Visuospatial Memory Test - Revised (BVMT-R) [ Time Frame: Up to 5 years ]
    Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).

  6. Change From Baseline in Cognition Test Scores of Symbol Digit Modality Test (SDMT) [ Time Frame: Up to 5 years ]
    Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).

  7. Change From Baseline in Quality of Life (QoL) Measures of Pediatric Quality of Life (PedsQL) Questionnaire Score [ Time Frame: Up to 5 years ]
    Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).

  8. Change From Baseline in Pediatric Quality of Life in Neurological Disorders (NeuroQoL) Questionnaire Score [ Time Frame: Up to 5 years ]
    Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).

  9. Serum Concentrations of Alemtuzumab Over Time [ Time Frame: Up to 5 years ]
    Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).

  10. Maximum Serum Concentration Observed (Cmax) of Alemtuzumab [ Time Frame: Up to 5 years ]
    Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).

  11. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alemtuzumab [ Time Frame: Up to 5 years ]
    Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).

  12. Area Under the Plasma Concentration-Time Curve (AUC) of Alemtuzumab [ Time Frame: Up to 5 years ]
    Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).

  13. Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Alemtuzumab [ Time Frame: Up to 5 years ]
    Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).

  14. Terminal Half-life (T1/2z) of Alemtuzumab [ Time Frame: Up to 5 years ]
    Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).

  15. Assessment of Lymphocyte Phenotyping [ Time Frame: Up to 5 years ]
    Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).

  16. Percentage of Participants With Incidence of Antidrug Antibodies (ADA) [ Time Frame: Up to 5 years ]
    Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2026).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   10 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03368664


Locations
Show Show 21 study locations
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Layout table for investigator information
Study Director: Clinical Sciences & Operations Sanofi
  Study Documents (Full-Text)

Documents provided by Sanofi ( Genzyme, a Sanofi Company ):
Study Protocol  [PDF] December 15, 2021
Statistical Analysis Plan  [PDF] January 17, 2018

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Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT03368664    
Other Study ID Numbers: EFC13429
2016-003100-30 ( EudraCT Number )
U1111-1180-6352 ( Other Identifier: UTN )
First Posted: December 11, 2017    Key Record Dates
Results First Posted: July 12, 2022
Last Update Posted: July 12, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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

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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
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Interferons
Acyclovir
Interferon-beta
Methylprednisolone
Prednisolone
Alemtuzumab
Glatiramer Acetate
Ranitidine
(T,G)-A-L
Dexchlorpheniramine
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones