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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)

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ClinicalTrials.gov Identifier: NCT03368664
Recruitment Status : Recruiting
First Posted : December 11, 2017
Last Update Posted : November 19, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Tracking Information
First Submitted Date  ICMJE November 2, 2017
First Posted Date  ICMJE December 11, 2017
Last Update Posted Date November 19, 2019
Actual Study Start Date  ICMJE October 24, 2017
Estimated Primary Completion Date July 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 28, 2019)
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 Disease Modifying Therapies (DMTs) (Period 1) compared to an equal period after the first course of alemtuzumab treatment (Period 2). -
Original Primary Outcome Measures  ICMJE
 (submitted: December 5, 2017)
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).
Change History Complete list of historical versions of study NCT03368664 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 28, 2019)
  • 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)
  • Change in Expanded Disability Status Scale (EDSS) [ Time Frame: Month 4 to month 8 (Period 2) ]
    Percentages of stable/improved/worsened since the end of Period 1
  • 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 years
  • 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
  • Assessment 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
  • Assessment of generic pediatric Quality of Life (QoL) measures [ Time Frame: Baseline to over 2 years ]
    Change from baseline in QoL measures of pediatric NeuroQoL questionnaire score over 2 years
  • Assessment of pharmacokiinetic (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 ]
    To evaluate area under the cumulative serum concentration versus time curve
  • Assessment of pharmacodynamic (PD) parameter: lymphocyte phenotyping [ Time Frame: Until Month 60 ]
    Lymphocyte phenotyping will be assessed at screening until M24/at EOTP; annually in Safety Monitoring Phase.
  • Safety: Adverse Events (AE) [ Time Frame: Baseline to over 2 years ]
    Adverse Events reported at each visit
  • Anti-drug Antibody (ADA) [ Time Frame: Visit 1 ]
    Assessment of development of antialemtuzumab antibodies at baseline
Original Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2017)
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Efficacy, Safety, and Tolerability of Alemtuzumab in Pediatric Patients With RRMS With Disease Activity on Prior DMT
Official Title  ICMJE 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)
Brief Summary

Primary Objective:

To evaluate the efficacy, safety, and tolerability of alemtuzumab intravenously (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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE
  • Drug: Alemtuzumab GZ402673
    Pharmaceutical form:solution Route of administration: intravenous
    Other Name: Lemtrada
  • Drug: Glatiramer acetate
    Pharmaceutical form:solution Route of administration: subcutaneous
    Other Name: Copaxone
  • Drug: Beta-Interferon
    Pharmaceutical form:solution Route of administration: subcutaneous / intramuscular
  • Drug: Methylprednisolone
    Pharmaceutical form:solution Route of administration: intravenous
  • 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: intravenous
  • Drug: Other H1 antagonist
    Pharmaceutical form:solution Route of administration: intravenous
  • Drug: Other H1 antagonist
    Pharmaceutical form:tablet/pill Route of administration: oral
Study Arms  ICMJE 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
Interventions:
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 5, 2017)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2026
Estimated Primary Completion Date July 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria :

  • Patients with Relapsing Remitting Multiple Sclerosis (RRMS) aged from 10 years to less than 18 years at study entry are eligible. Patients must 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 2010 McDonald criteria.
  • Signed written 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 beta interferon therapy (IFNB) or glatiramer acetate (GA) after having been on that therapy for at least 6 months, and is 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 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. Patients who were treated with a comparator agent approved for screening inclusion (INF or GA) may be considered for this trial.
  • 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 highly effective contraceptive method 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 10 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-US@sanofi.com
Listed Location Countries  ICMJE Austria,   Belgium,   Bulgaria,   Czechia,   France,   Germany,   Greece,   Italy,   Netherlands,   Norway,   Poland,   Portugal,   Russian Federation,   Spain,   Turkey,   United Kingdom
Removed Location Countries Switzerland
 
Administrative Information
NCT Number  ICMJE NCT03368664
Other Study ID Numbers  ICMJE EFC13429
2016-003100-30 ( EudraCT Number )
U1111-1180-6352 ( Other Identifier: UTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
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://www.clinicalstudydatarequest.com/
Responsible Party Sanofi ( Genzyme, a Sanofi Company )
Study Sponsor  ICMJE Genzyme, a Sanofi Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP