Multiple Sclerosis
Conditions
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).
Detailed description
The duration of study per participant will be approximately 5 years and 5 months.
Interventions
Pharmaceutical form: solution, Route of administration: IV
DRUGGlatiramer acetate
Pharmaceutical form: solution, Route of administration: subcutaneous (SC)
DRUGBeta-Interferon
Pharmaceutical form: solution, Route of administration: SC / intramuscular (IM)
DRUGMethylprednisolone
Pharmaceutical form: solution, Route of administration: IV
DRUGRanitidine
Pharmaceutical form: tablet, Route of administration: oral
DRUGCeterizine
Pharmaceutical form: tablet, Route of administration: oral
Pharmaceutical form: tablet, Route of administration: oral
DRUGParacetamol
Pharmaceutical form: tablet, Route of administration: oral
DRUGAcyclovir
Pharmaceutical form: tablet, Route of administration: oral
DRUGPrednisolone
Pharmaceutical form: tablet, Route of administration: oral
DRUGDiphenydramine
Pharmaceutical form: solution, Route of administration: IV
DRUGOther H1 antagonist
Pharmaceutical form: solution, Route of administration: IV
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan | 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
| Measure | Time frame | Description |
|---|---|---|
| Terminal Half-life (T1/2z) of Alemtuzumab | 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). |
| Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Months 4 and 8 | 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAE) | 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). |
| Annualized Relapse Rate (ARR) | 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). |
| Change From Baseline in Cognition Test Scores of Brief Visuospatial Memory Test - Revised (BVMT-R) | 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). |
| Change From Baseline in Cognition Test Scores of Symbol Digit Modality Test (SDMT) | 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). |
| Change From Baseline in Quality of Life (QoL) Measures of Pediatric Quality of Life (PedsQL) Questionnaire Score | 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). |
| Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Participants With New or Enlarged T2 Lesions Per MRI Scan | 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. |
| Serum Concentrations of Alemtuzumab Over Time | 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). |
| Maximum Serum Concentration Observed (Cmax) of Alemtuzumab | 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). |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alemtuzumab | 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). |
| Area Under the Plasma Concentration-Time Curve (AUC) of Alemtuzumab | 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). |
| Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Alemtuzumab | 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). |
| Assessment of Lymphocyte Phenotyping | 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). |
| Percentage of Participants With Incidence of Antidrug Antibodies (ADA) | 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). |
| Change From Baseline in Pediatric Quality of Life in Neurological Disorders (NeuroQoL) Questionnaire Score | 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). |
Countries
Austria, France, Italy, Poland, Russia, Turkey (Türkiye), United Kingdom
Participant flow
Recruitment details
The study is being conducted at 21 sites in 10 countries. A total of 16 participants were screened and enrolled between 24-October-2017 and 07-September-2020.
Pre-assignment details
Prior to alemtuzumab treatment phase (Month 0 to Month 8), participants underwent prior disease modifying therapy (DMT) phase during Month -4 to Month 0 (conducted to check participants eligibility for treatment). The DMT was discontinued 7 days prior to administration of first dose of alemtuzumab at Month 0. Data reported based on primary completion date of 04-May-2021.
Participants by arm
| Arm | Count |
|---|---|
| Alemtuzumab Participants with RRMS underwent prior DMT, from Month -4 to Month 0 (conducted to check participants eligibility for treatment) in prior DMT phase. After DMT phase, participants who were eligible for treatment, and with body weight \>=50 kg received 12 mg/day of alemtuzumab, and participants with body weight \<50 kg received 0.24 mg/kg/day of alemtuzumab administered as daily IV infusions at Month 0 for 5 consecutive days as first course of study treatment in alemtuzumab treatment phase. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Phase1: Prior DMT:Month -4 to Month 0 | Participant was withdrawn from study | 1 |
| Phase1: Prior DMT:Month -4 to Month 0 | Physician Decision | 1 |
| Phase1: Prior DMT:Month -4 to Month 0 | Principal Investigator and Parents Decision | 1 |
| Phase1: Prior DMT:Month -4 to Month 0 | Still on Prior DMT Phase or missing Completion | 1 |
Baseline characteristics
| Characteristic | Alemtuzumab |
|---|---|
| Age, Continuous | 14.5 years STANDARD_DEVIATION 2.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 11 |
| other Total, other adverse events | 10 / 16 | 11 / 11 |
| serious Total, serious adverse events | 3 / 16 | 3 / 11 |
Outcome results
Primary
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.
Time frame: Period 1: Month -4 up to Month 0, Period 2: Month 4 to Month 8
Population: Analysis was performed on modified intent-to-treat (mITT) population that included participants who had received at least 1 dose of alemtuzumab and also had evaluable data for both Period 1 and Period 2. Data for this outcome measure was planned to be collected and analyzed separately for both periods.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period 1 | Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan | 3.53 lesions per scan |
| Period 2 | Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan | 0.13 lesions per scan |
Secondary
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).
Time frame: Up to 5 years
Secondary
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).
Time frame: Up to 5 years
Secondary
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).
Time frame: Up to 5 years
Secondary
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).
Time frame: Up to 5 years
Secondary
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.
Time frame: Period 1: Month -4 up to Month 0, Period 2: Month 4 to Month 8
Population: Analysis was performed on mITT population. Data for this outcome measure was planned to be collected and analyzed separately for both periods.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Period 1 | Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Participants With New or Enlarged T2 Lesions Per MRI Scan | 10 Participants |
| Period 2 | Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Participants With New or Enlarged T2 Lesions Per MRI Scan | 3 Participants |
Secondary
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).
Time frame: Up to 5 years
Secondary
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).
Time frame: Up to 5 years
Secondary
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.
Time frame: Baseline, Months 4 and 8
Population: Analysis was performed on mITT population. Here, 'number analyzed' signifies participants with available data for each specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1 | Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Months 4 and 8 | Month 4 | 0.05 scores on scale | Standard Deviation 0.52 |
| Period 1 | Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Months 4 and 8 | Month 8 | 0.00 scores on scale | Standard Deviation 0.55 |
Secondary
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).
Time frame: Up to 5 years
Secondary
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).
Time frame: Up to 5 years
Secondary
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).
Time frame: Up to 5 years
Secondary
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).
Time frame: Up to 5 years
Secondary
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).
Time frame: Up to 5 years
Secondary
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).
Time frame: Up to 5 years
Secondary
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).
Time frame: Up to 5 years
Secondary
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).
Time frame: Up to 5 years