A study of BG00012 on MRI lesions and Pharmacokinetics in children from 10 to less than 18 years old with a type of Multiple Sclerosis called 'Relapsing, Remitting Multiple Sclerosis'

• Register: EUCTR
• Last refreshed on: 10 October 2016
• Main ID: EUCTR2014-005003-24-CZ
• Date of registration: 02/03/2015
• Prospective Registration: Yes
• Primary sponsor: Biogen Idec Research Limited
• Public title: A study of BG00012 on MRI lesions and Pharmacokinetics in children from 10 to less than 18 years old with a type of Multiple Sclerosis called 'Relapsing, Remitting Multiple Sclerosis'
• Scientific title: Open-Label, Multicenter, Multiple-Dose Study of the Effect of BG00012 on MRI Lesions and Pharmacokinetics in Pediatric Subjects With Relapsing-Remitting Multiple Sclerosis Aged 10 to 17 Years
• Date of first enrolment: 21/09/2015
• Target sample size: 18
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005003-24
• 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: Placebo: Other: Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Bulgaria, Czech Republic, Germany, Israel, Italy, Kuwait, Latvia, Lebanon, Lithuania, Poland, Turkey, United States

Contacts

• Name: Clinical Trials - Neurology
• Affiliation: Biogen Idec Research Limited

• Name: Clinical Trials - Neurology
• Affiliation: Biogen Idec Research Limited

Key inclusion & exclusion criteria

Inclusion criteria:
To be eligible to participate in this study, candidates must meet the following eligibility criteria at Screening or at the timepoint specified in the individual eligibility criterion listed:

1. Ability of parents or legal guardians to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local subject privacy regulations. Subjects will provide assent in addition to the parent or legal guardian, as appropriate, as per local regulations.

2. Male and female subjects aged 10 to 17 years old, inclusive, at the time of informed consent.

3. Must have a body weight of =30 kg at Screening and Day 1.

4. Must have a diagnosis of RRMS according to McDonald criteria for MS (2010) [Polman 2011] and International Pediatric Multiple Sclerosis Study Group criteria for pediatric MS (2013) [Krupp 2013].

5. Must be ambulatory, with a converted Kurtzke baseline EDSS score between 0 and 5.0, inclusive.

6. Must have experienced =1 relapse in the 12 months prior to Screening or =2 relapses in the 24 months prior to Screening.

7. Must agree to be without treatment for 8 weeks prior to Day 1.

8. Sexually active subjects of reproductive potential must practice effective contraception during the study and for at least 30 days after their last dose of study treatment. For further details of contraceptive requirements for this study, refer to the protocol.
Are the trial subjects under 18? yes
Number of subjects for this age range: 18
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:
Candidates will be excluded from study entry if any of the following exclusion criteria exist at Screening or at the timepoint specified in the individual criterion listed:

1. Primary progressive, secondary progressive, or progressive relapsing MS (as defined by [Lublin and Reingold 1996]). These conditions require the presence of continuous clinical disease worsening over a period of at least 3 months. Subjects with these conditions may also have superimposed relapses but are distinguished from relapsing-remitting subjects by the lack of clinically stable periods or clinical improvement.

2. Disorders mimicking MS, such as other demyelinating disorders (e.g., acute disseminated encephalomyelitis), systemic autoimmune disorders (e.g., Sjögren disease, lupus erythematosus, and neuromyelitis optica), metabolic disorders (e.g., dystrophies), and infectious disorders.

3. History of premalignant or malignant disease. Subjects with basal cell carcinoma that has been completely excised prior to Screening will remain eligible.

4. History of severe allergic or anaphylactic reactions or known drug hypersensitivity to DMF or fumaric acid esters.

5. History of any clinically significant cardiovascular, dermatologic, endocrinologic, GI, hematologic, immunologic, growth, developmental, pulmonary, psychiatric, neurologic (other than MS), renal, urologic, and/or other major disease that may confound safety or efficacy assessment.

6. History of drug or alcohol abuse (as defined by the Investigator) within the 2 years prior to Screening.

7. Any of the following abnormal blood tests at Screening:
- alanine transaminase (ALT)/serum glutamic pyruvic transaminase (SGPT), AST/serum glutamic oxaloacetic transaminase (SGOT), or gamma glutamyl transferase (GGT) =2 times the upper limit of normal
- leukocytes <3500/mm3
- absolute lymphocyte count - eosinophils >0.7 × 103/µL or >0.7 GI/L

8. Any of the following abnormal urine tests at Screening confirmed by a second urinalysis 2 weeks later:
- proteinuria (1+ or greater) and/or spot protein/creatinine ratio (with AM void) >0.2 mg. Note: Documented benign proteinuria is not exclusionary.
- hematuria, without known etiology (e.g., urinary tract infection or menses)
- glycosuria, without known etiology (e.g., recent steroid use or elevated serum glucose)

9. History of or positive test result at Screening for human immunodeficiency virus.

10. History of or positive test result at Screening for hepatitis C virus antibody or hepatitis B virus (defined as positive for hepatitis B surface antigen [HBsAg]or hepatitis B core antibody [HBcAb]). Subjects with immunity to hepatitis B from either active vaccination (defined as negative HBsAg, positive hepatitis B surface antibody [HBsAb], and negative HBcAb) or from previous natural infection (defined as negative HBsAg, positive HBsAb immunoglobulin G, and positive HBcAb) are eligible to participate in the study (definitions are based on the US Centers for Disease Control and Prevention’s interpretation of the hepatitis B serology panel [CDC 2007]).

Treatment History
11. Any previous treatment with Fumaderm® or BG00012.

12. Prior treatment with any of the following:
- total lymphoid irradiation
- cladribine
- T-cell or T-cell receptor vaccination
- any therapeutic monoclonal antibody, with the exception of rituximab or natalizumab

13. Prior treatment with any of the following medications within the 12 months prior to the

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

Health Condition(s) or Problem(s) studied

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

Relapsing-Remitting Multiple Sclerosis
MedDRA version: 19.0 Level: SOC Classification code 10029205 Term: Nervous system disorders System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 19.0 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: BG00012
Pharmaceutical Form: Gastro-resistant capsule, hard
INN or Proposed INN: DIMETHYL FUMARATE
CAS Number: 624-49-7
Current Sponsor code: BG00012
Other descriptive name: DIMETHYL FUMARATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 120-

Primary Outcome(s)

Secondary Objective: The secondary objectives of this study are as follows:
- To characterize the PK of BG00012 in paediatric subjects with RRMS
- To evaluate the safety and tolerability of BG00012 in paediatric subjects with RRMS

Timepoint(s) of evaluation of this end point: Baseline period (Week -8 to Day 0), weeks 16 & 24

Main Objective: The primary objective of this study is to evaluate the effect of BG00012 on brain MRI lesions in paediatric subjects with RRMS

Primary end point(s): Change from Baseline Period to On-Treatment Assessment Period in the number of new or newly enlarging T2 hyperintense lesions on brain MRI scans, where the Baseline Period is from Week -8 to Day 0 and the On-Treatment Assessment Period is from Week 16 to Week 24

Secondary Outcome(s)

Secondary end point(s): The secondary endpoints of this study are as follows:
- PK parameters: Cmax, time to reach maximum observed plasma concentration (Tmax), apparent clearance (CL/F), apparent volume of distribution (V/F), elimination half-life (t½), and area under the concentration-time curve from time 0 to infinity (AUC0-inf)

- Incidence of treatment-emergent adverse events (AEs) and serious adverse events (SAEs)

Timepoint(s) of evaluation of this end point: PK Assessments:
Day 1 (within 2 hrs prior to dose, 2 hrs post-dose, 3 hrs post-dose).
Day 8 (within 2 hrs prior to dose, 30 mins post-dose and 1, 2, 3, 4, 5, 6, 8, 10 hrs post-dose).

AEs and SAEs:
For AEs monitoring is from Week -8 MRI Visit up to the Safety Follow-Up Visit, or from the Week -8 MRI Visit up to the Week 24 Visit for subjects enrolling in the extension study.

For SAEs monitoring is from the signing of ICF and assent up to the Safety Follow-Up Visit, or from the signing the ICF up to the Week 24 Visit for subjects enrolling in the extension study. Any SAE that is ongoing when the subject completes or discontinues the study will be followed by the Investigator until the event has resolved, stabilized, or returned to baseline status

Secondary ID(s)

109MS202

2014-005003-24-LV

Source(s) of Monetary Support

Biogen Idec Research Limited