| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsing Remitting Multiple Sclerosis (RRMS) |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | SOC |
| E.1.2 | Classification code | 10029205 |
| E.1.2 | Term | Nervous system disorders |
| E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10063399 |
| E.1.2 | Term | Relapsing-remitting multiple sclerosis |
| E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
This study will evaluate the safety, tolerability, and descriptive efficacy of BIIB017 in pediatric participants with relapsing-remitting multiple sclerosis
(RRMS) and to assess the pharmacokinetics (PK) of BIIB017 in pediatric participants with RRMS in Part 1. In Part 2, the study will evaluate the long-term
safety of BIIB017 and further describe safety and the long-term multiple sclerosis (MS) outcomes after BIIB017 treatment in participants who completed
the study treatment at Week 96 in Part 1 of the study. |
|
| E.2.2 | Secondary objectives of the trial | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Part 1
1. Must have a diagnosis of RRMS as defined by the revised consensus definition for
pediatric MS [Krupp 2013; Polman 2011].
2. Must have an EDSS score between 0.0 and 5.5.
3. Must have experienced ≥1 relapse in the 12 months prior to randomization (Day 1) or
≥2 relapses in the 24 months prior to randomization (Day 1) or have evidence of
asymptomatic disease activity (Gd-enhancing lesions) on brain MRI in the 6 months prior
to randomization (Day 1).
Part 2
Subjects who completed the study treatment in Part 1 (Week 96 Visit), as per protocol. |
|
| E.4 | Principal exclusion criteria |
PART 1
1. Primary progressive, secondary progressive, or progressive relapsing MS .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 subjects by the lack of clinically stable periods or clinical improvement.
2. Occurrence of an MS relapse that has occurred within 30 days prior to randomization (Day 1) and/or the subject has not stabilized from a previous relapse prior to randomization (Day 1).
3. History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
4. Known allergy to any component of Avonex or BIIB017 formulation.
5. Any previous treatment with PEGylated human IFN β-1a.
PART 2
1. Any significant changes in medical history occurring after enrollment in Part 1, including laboratory test abnormalities or current clinically significant conditions that, in the opinion of the Investigator, would have excluded the subject’s participation in Part 1.
The Investigator must re-assess the subject’s medical fitness for participation and consider any factors that would preclude treatment.
2. The subject could not tolerate BIIB017 in Part 1.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
#1: Part 1: the annualized relapse rate (ARR) at Week 48.
#2: Part 2: Percentage of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs leading to Study Treatment Discontinuation. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
#1: week 48
#2: Week 96 to Week 196 |
|
| E.5.2 | Secondary end point(s) |
PART 1:
#3: ARR at Week 96
#4: percentage of subjects free of new or newly enlarging T2 hyperintense lesions on brain magnetic resonance imaging (MRI) scans at Weeks 24, 48, and 96
#5: percentage of subjects free of new MRI activity in the brain (free of gadolinium [Gd]-enhancing lesions and new or newly enlarging T2 hyperintense lesions) at Weeks 24, 48, and 96
#6: Number of New or Nely Enlarging T2 Hyperintense Lesions on Brain MRI Scans at Weeks 24, 48 and 96
#7: Number of GD-Enhancing Lesions on Brain MRI Scans at Weeks 24, 48 and 96
#8: Time to First Relapse (timeframe up to week 96)
#9: Percentage of Participants Free of Relapse at Weeks 48 and 96 (Timeframe weeks 48 and 96)
#10: Change from Baseline in Cognition at Weeks 24, 28, 72 and 96 as Measured by the Symbol Digit Modality Test (SDMT)
#11: Change from Baseline in the Expanded Disability Status Scale (EDSS) Score at Weeks 48 and 96
#12: Change from Baseline in the Quality of Life as Measured by the Pediatric Quality of Live Inventory (PedsQL) at Weeks 24, 48, 72 and 96.
#13: Area Under the Plasma Concentration – Time Cruve from Time Zero to End of Dosing Interval (AUCtau) for BIIB017
#14: Maximum Observed Plasma Concentration (Cmax) at Steady State for BIIB017
#15: Time to Reach Maximum Observed Plasma Concentration (Tmax) at Steady State for BIIB017
#16: Percentage of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Treatment Discontinuation
#17: Change from Baseline in Height at Weeks 24, 48, 72, 96 and 100
#18: Change from Baseline in Weight at Weeks 24, 48, 72, 96 and 100
#19: Change from Baseline in Tanner Score at Weeks 24, 48, 72, 96 and 100
#20: Number of Participants With Binding and Neutralizing Antibodies to Interferon Beta Type 1a (IFN β-1a)
#21: Number of Participants with Binding Antibodies to Peginterferon (PEG) [BIIB017-Treated Participants]
#22: Change from Baseline in Depression as Assessed by Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) at Weeks 12, 24, 36, 48, 60, 72, 84, 96 and 100
#23: Change from Baseline in Blood Pressure at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96 and 100
#24: Change from Baseline in Pulse Rate at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96 and 100
#25: Change from Baseline in Body Temperature at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96 and 100
#26: Change from Baseline in Respiratory Rate at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96 and 100
#27: Change from Baseline in 12-Lead Electrocardiogram (ECG) Parameters at Weeks 48, 96 and 100
#28: Percentage of Participants with Changes Over Time in Clinical Laboratory Values
Part 2
#29: ARR at Weeks 144 and 192
#30: Change from Baseline in EDSS Score at Weeks 120, 144, 168, 192 and 196
#31: Change from Baseline in Height at Weeks 120, 144, 168, 192 and 196
#32: Change from Baseline in Weight at Weeks 120, 144, 168, 192 and 196
#33: Change from Baseline in Tanner Score at Weeks 120, 144, 168, 192 and 196
#34: Number of Participants with Binding and Neutralizing Antibodies to IFN β-1a (All Participants)
#35: Number of Participants with Binding Antibodies to PEG (BIIB017-Treated Participants)
#36: Change from Baseline in Blood Pressure at Weeks 120, 144, 168, 192 and 196
#37: Change from Baseline in Pulse Rate at Weeks 120, 144, 168, 192 and 196
#38: Change from Baseline in Body Temperature at Weeks 120, 144, 168, 192 and 196
#39: Change from Baseline in Respiratory Rate at Weeks 120, 144, 168, 192 and 196
#40: Change from Baseline in 12-Lead ECG Parameters at Weeks 144, 192 and 196
#41: Change from Baseline in Depression as Assessed by Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) at Weeks 108, 120, 132, 144, 156, 168, 180, 192 and 196.
#42: Percentage of Participants with Changes Over Time in Clinical Laboratory Values. Clinical laboratory tests include: hematology, chemistry (including liver, renal and thyroid function) and coagulation tests
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Timepoints for Part 1 & 2 are specified above |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 47 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Tunisia |
| Australia |
| Israel |
| Kuwait |
| Mexico |
| Russian Federation |
| Saudi Arabia |
| Serbia |
| United States |
| Belgium |
| Bulgaria |
| Croatia |
| Czechia |
| France |
| Germany |
| Greece |
| Hungary |
| Italy |
| Portugal |
| Slovakia |
| Spain |
| Türkiye |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of study is last subject, last visit for final collection of data. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 10 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 15 |
| E.8.9.2 | In all countries concerned by the trial years | 10 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
Print
