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

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2016-003100-30-ES
• Date of registration: 22/02/2017
• Prospective Registration: Yes
• Primary sponsor: Genzyme Corporation
• Public title: A Study to Evaluate Efficacy, Safety, and Tolerability of Alemtuzumab in Pediatric Patients with RRMS with Disease Activity on Prior DMT
• Scientific title: A Multi-center, Open-label, Single-arm, Before and After Switch Study to Evaluate the Efficacy, Safety and Tolerability of Alemtuzumab in Pediatric Patients with Relapsing Remitting Multiple Sclerosis (RRMS) with Disease Activity on Prior Disease Modifying Therapy (DMT)
• Date of first enrolment: 04/04/2017
• Target sample size: 65
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003100-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Bulgaria, Czech Republic, France, Germany, Greece, Italy, Netherlands, Norway, Poland, Portugal, Russian Federation, Spain, Sweden, Switzerland, Turkey, United Kingdom

Contacts

• Name: Unidad Estudios Clínicos
• Affiliation: sanofi-aventis, s.a.

• Name: Unidad Estudios Clínicos
• Affiliation: sanofi-aventis, s.a.

Key inclusion & exclusion criteria

Inclusion criteria:
-Patients with RRMS aged from 10 years to less than 18 years at study entry are eligible. Patients should meet the criteria of diagnosis of MS as defined by the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for pediatric MS and the criteria of MS based on McDonald criteria 2010.
-Signed 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 MS attacks and at least 1 MS attack (relapse) in the last year during treatment with a interferon-beta (IFNB) or glatiramer acetate (GA) after having been on that therapy for at least 6 months
-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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 65
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.
-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 tothe 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 reliable and effective contraceptive method as defined for contraception in the Informed Consent form (ICF) when receiving a course of alemtuzumab treatment and for 4 months following that course of treatmenty (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 as 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 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 exci

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Multiple Sclerosis
MedDRA version: 19.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: Lemtrada
Product Name: Lemtrada
Product Code: GZ402673
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: alemtuzumab
CAS Number: 216503-57-0
Current Sponsor code: GZ402673
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Primary end point(s): Number of 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)

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).

Timepoint(s) of evaluation of this end point: 12 months

Main Objective: To evaluate the efficacy, safety, and tolerability of alemtuzumab (IV) in pediatric patients from 10 to <18 years of age with RRMS who have disease activity on prior DMT.

Secondary Outcome(s)

Secondary end point(s): 1) Number 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)
2) Annualized relapse rate (ARR)
3) Assessment of cognition test scores throught Brief Visuospatial
Memory Test
4) Assesment of generic pediatric QoL measures
5) Assessment of PK parameter: maximum concentration (Cmax)
6) Assessment of PK parameter: time to Cmax (Tmax)
7) Assessment of PK parameter: area under plasma concentration
(AUC)
8) Assessment of PD parameter: lymphocite phenotyping
9) Number of patients with adverse events
10) Assessment of development of anti-alemtuzumab antibodies

Timepoint(s) of evaluation of this end point: 1) 12 months
2) at year 2
3) and 4) every 6 months over 2 years
5) to 7) 2 years
8) until month 60
9) 4 years after last dose of alemtuzumab
10) at Baseline, month 1, month 3, month 12, month 13, month 15, month 24

Secondary ID(s)

EFC13429

Source(s) of Monetary Support

Genzyme Corporation

Ethics review

Status: Approved
Approval date:
Contact: