A Study to Evaluate the Safety, Tolerability, and Efficacy of BIIB017 (Peginterferon beta-1a) in Pediatric Participants for the Treatment of Relapsing-Remitting Multiple Sclerosis (105MS306)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biogen Idec Research Limited

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

7 Aug 2019 → ongoing

Decision date (initial)

2024-11-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Biogen Idec Research Limited

External identifiers

EU CT number

2023-505624-56-00

EudraCT number

2018-003008-38

ClinicalTrials.gov

NCT03958877

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Therapy

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.

Secondary objectives 1

1. Not applicable, refer to prior section

Conditions and MedDRA coding

Relapsing Remitting Multiple Sclerosis (RRMS)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-469210-PIP20-23

Plan to share IPD

Yes

IPD plan description

In accordance with Biogen’s Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. [Part I] Must have a diagnosis of RRMS as defined by the revised consensus definition for pediatric MS
2. [Part I] Must have an EDSS score between 0.0 and 5.5
3. [Part I] 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).
4. [Part II] Participants who completed the study treatment in Part 1 (Week 96 Visit), as per protocol.

Exclusion criteria 7

1. [Part I] 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. Participants 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. [Part I] History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
3. Known allergy to any component of Avonex or BIIB017 formulation.
4. Occurrence of an MS relapse that has occurred within 30 days prior to randomization (Day 1) and/or the participant has not stabilized from a previous relapse prior to randomization (Day 1).
5. [Part I] Any previous treatment with PEGylated human IFN β-1a
6. [Part II] Any significant changes in medical history occurring after enrolment 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.
7. [Part II] The subject could not tolerate BIIB017 in Part 1. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

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. [From Week 96 to week 196]

Secondary endpoints 39

1. [Part I] ARR at week 48
2. [Part I] Percentage of Participants Free of New or Newly Enlarging T2 Hyperintense Lesions on Brain Magnetic Resonance Imaging (MRI) Scans at Weeks 24, 48, and 96
3. [Part I] Percentage of Participants 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
4. [Part I] Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans at Weeks 24, 48, and 96
5. [Part I] Number of Gd-Enhancing Lesions on Brain MRI Scans at Weeks 24, 48, and 96
6. [Part I] Time to First Relapse (timeframe: Up to week 96).
7. [Part I] Percentage of Participants Free of Relapse at Weeks 48 and 96.
8. [Part I] Change from Baseline in Cognition at Weeks 24, 48, 72, and 96 as Measured by the Symbol Digit Modality Test (SDMT)
9. [Part I] Change from Baseline in the Expanded Disability Status Scale (EDSS) Score at Weeks 48 and 96
10. [Part I] Change from Baseline in the Quality of Life as Measured by the Pediatric Quality of Life Inventory (PedsQL) at Weeks 24, 48, 72 and 96
11. [Part I] Area Under the Plasma Concentration-Time Curve from Time Zero to End of Dosing Interval (AUCtau) for BIIB017. [Time Frame: Within 8 hours postdose on Day 1 of Week 1; Within 8 hours, 48 and 120 hours postdose on Day 1 of Week 4; Within 8 hours postdose on Day 1 of Week 24]
12. [Part I] Part 1: Maximum Observed Plasma Concentration (Cmax) at Steady State for BIIB017 Within 8 hours postdose on Day 1 of Week 1; Within 8 hours, 48 and 120 hours postdose on Day 1 of Week 4; Within 8 hours postdose on Day 1 of Week 24
13. [Part I] Time to Reach Maximum Observed Plasma Concentration (Tmax) at Steady State for BIIB017 Within 8 hours postdose on Day 1 of Week 1; Within 8 hours, 48 and 120 hours postdose on Day 1 of Week 4; Within 8 hours postdose on Day 1 of Week 24
14. [Part I] Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Treatment Discontinuation (timeframe up to week 100)
15. [Part I] Change from Baseline in Height at Weeks 24, 48, 72, 96, and 100
16. [Part I] Change from Baseline in Weight at Weeks 24, 48, 72, 96, and 100
17. [Part I] Number of Participants With Binding and Neutralizing Antibodies to Interferon Beta Type 1a (IFN β-1a) [All Participants] [Time Frame: Up to Week 96]
18. [Part I] Number of Participants With Binding Antibodies to Peginterferon (PEG) [BIIB017-Treated Participants] Anti-PEG binding antibodies in human serum will be determined using an ELISA (Timeframe: Up to Week 96)
19. [Part I] 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
20. [Part I] Change from Baseline in Blood Pressure at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 10
21. [Part I] Change from Baseline in Pulse Rate at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
22. [Part I] Change from Baseline in Body Temperature at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
23. [Part I] Change from Baseline in Respiratory Rate at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
24. [Part I] Change from Baseline in 12-Lead Electrocardiogram (ECG) Parameters at Weeks 48, 96, and 100
25. [Part I] Percentage of Participants with Changes Over Time in Clinical Laboratory Values at Baseline & Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
26. Part 2: ARR at Weeks 144 and 192
27. Part 2: Change from Baseline in EDSS Score at Weeks 120, 144, 168, 192, and 196
28. Part 2: Change from Baseline in Height at Weeks 120, 144, 168, 192, and 196
29. Part 2: Change from Baseline in Weight at Weeks 120, 144, 168, 192, and 196
30. Part 2: Change from Baseline in Tanner Score at Weeks 120, 144, 168, 192, and 196
31. Part 2: Number of Participants With Binding and Neutralizing Antibodies to IFN β-1a (All Participants) (Time Frame: Up to week 192)
32. Part 2: Number of Participants With Binding Antibodies to PEG (BIIB017-Treated Participants) (Time Frame: Up to week 192)
33. Part 2: Change from Baseline in Blood Pressure at Weeks 120,144,168, 192, and 196
34. Part 2: Change from Baseline in Pulse Rate at Weeks 120, 144, 168, 192, and 196
35. Part 2: Change from Baseline in Body Temperature at Weeks 120, 144, 168, 192, and 196
36. Part 2: Change from Baseline in Respiratory Rate at Weeks 120, 144, 168, 192, and 196
37. Part 2: Change from Baseline in 12-Lead ECG Parameters at Weeks 144, 192, and 196
38. Part 2: 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
39. Part 2: Percentage of Participants with Changes Over Time in Clinical Laboratory Values at Baseline & (Week 96), Weeks 108, 120, 132, 144, 156, 168, 180, 192, and 196

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biogen Idec Research Limited

Sponsor organisation

Biogen Idec Research Limited

Address

Innovation House, 70 Norden Road 70 Norden Road

City

Maidenhead

Postcode

SL6 4AY

Country

United Kingdom

Scientific contact point

Organisation

Biogen Idec Research Limited

Contact name

Clinical Trials Information Desk

Public contact point

Organisation

Biogen Idec Research Limited

Contact name

Clinical Trials Information Desk

Third parties 17

Locations

5 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 150 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications