Clinical trial NCT03368664: A Study to Evaluate Efficacy, Safety, and Tolerability of Alemtuzumab in Pediatric Patients With RRMS With Disease Activity on Prior DMT
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Multiple Sclerosis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2017-12-11
Enrollment: 16
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan
timeFrame: Period 1: Month -4 up to Month 0, Period 2: Month 4 to Month 8
Secondary outcomes:
measure: Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Participants With New or Enlarged T2 Lesions Per MRI Scan
timeFrame: Period 1: Month -4 up to Month 0, Period 2: Month 4 to Month 8
measure: Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Months 4 and 8
timeFrame: Baseline, Months 4 and 8
measure: Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAE)
timeFrame: Up to 5 years
measure: Annualized Relapse Rate (ARR)
timeFrame: Up to 5 years
measure: Change From Baseline in Cognition Test Scores of Brief Visuospatial Memory Test - Revised (BVMT-R)
timeFrame: Up to 5 years
measure: Change From Baseline in Cognition Test Scores of Symbol Digit Modality Test (SDMT)
timeFrame: Up to 5 years
measure: Change From Baseline in Quality of Life (QoL) Measures of Pediatric Quality of Life (PedsQL) Questionnaire Score
timeFrame: Up to 5 years
measure: Change From Baseline in Pediatric Quality of Life in Neurological Disorders (NeuroQoL) Questionnaire Score
timeFrame: Up to 5 years
measure: Serum Concentrations of Alemtuzumab Over Time
timeFrame: Up to 5 years
measure: Maximum Serum Concentration Observed (Cmax) of Alemtuzumab
timeFrame: Up to 5 years
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alemtuzumab
timeFrame: Up to 5 years
measure: Area Under the Plasma Concentration-Time Curve (AUC) of Alemtuzumab
timeFrame: Up to 5 years
measure: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Alemtuzumab
timeFrame: Up to 5 years
measure: Terminal Half-life (T1/2z) of Alemtuzumab
timeFrame: Up to 5 years
measure: Assessment of Lymphocyte Phenotyping
timeFrame: Up to 5 years
measure: Percentage of Participants With Incidence of Antidrug Antibodies (ADA)
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Wien
country: Austria
facility: Investigational Site Number :0400001
city: Gent
country: Belgium
facility: Investigational Site Number :0560001
city: Le Kremlin Bicetre
country: France
facility: Investigational Site Number :2500001
city: Strasbourg
country: France
facility: Investigational Site Number :2500002
city: Cagliari
country: Italy
facility: Investigational Site Number :3800005
city: Milano
country: Italy
facility: Investigational Site Number :3800001
city: Napoli
country: Italy
facility: Investigational Site Number :3800004
city: Rotterdam
country: Netherlands
facility: Investigational Site Number :5280001
city: Lodz
country: Poland
facility: Investigational Site Number :6160003
state: Lódzkie
city: Poznan
country: Poland
facility: Investigational Site Number :6160002
state: Wielkopolskie
city: Warszawa
country: Poland
facility: Investigational Site Number :6160001
city: Coimbra
country: Portugal
facility: Investigational Site Number :6200001
city: Moscow
country: Russian Federation
facility: Investigational Site Number :6430001
city: Moscow
country: Russian Federation
facility: Investigational Site Number :6430004
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number :6430005
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number :6430002
city: Ankara
country: Turkey
facility: Investigational Site Number :7920002
city: Ankara
country: Turkey
facility: Investigational Site Number :7920001
city: Istanbul
country: Turkey
facility: Investigational Site Number :7920003
city: Istanbul
country: Turkey
facility: Investigational Site Number :7920004
city: London
country: United Kingdom
facility: Investigational Site Number :8260002
state: London, City Of
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: