Clinical trial NCT03958877: 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
Official title: An Open-Label, Randomized, Multicenter, Active-Controlled, Parallel-Group Study to Evaluate the Safety, Tolerability, and Efficacy of BIIB017 in Pediatric Subjects Aged 10 to Less Than 18 Years for the Treatment of Relapsing-Remitting Multiple Sclerosis, With Optional Open-Label Extension
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Multiple Sclerosis, Relapsing-Remitting
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2019-05-22
Enrollment: 142
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Key Inclusion Criteria:

Part 1:

* Must have a diagnosis of RRMS as defined by the revised consensus definition for pediatric MS.
* Must have an EDSS score between 0.0 and 5.5.
* 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:

• Participants who completed the study treatment in Part 1 (Week 96 Visit), as per protocol.

Key Exclusion Criteria:

Part 1:

* Primary progressive, secondary progressive, or progressive relapsing. 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 participants by the lack of clinically stable periods or clinical improvement.
* History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
* Known allergy to any component of Avonex or BIIB017 formulation.
* 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).
* Any previous treatment with PEGylated human IFN β-1a.

Part 2:

* 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 participant's participation in Part 1. The Investigator must re-assess the participant's medical fitness for participation and consider any factors that would preclude treatment.
* The participant could not tolerate BIIB017 in Part 1.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply"

Primary outcomes:
measure: Part 1: Annualized Relapse Rate (ARR) at Week 48
timeFrame: Week 48
measure: Part 2: Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Treatment Discontinuation
timeFrame: From Week 96 to Week 196
Secondary outcomes:
measure: Part 1: ARR at Week 96
timeFrame: Week 96
measure: Part 1: 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
timeFrame: Weeks 24, 48, and 96
measure: Part 1: 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
timeFrame: Weeks 24, 48, and 96
measure: Part 1: Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans at Weeks 24, 48, and 96
timeFrame: Weeks 24, 48, and 96
measure: Part 1: Number of Gd-Enhancing Lesions on Brain MRI Scans at Weeks 24, 48, and 96
timeFrame: Weeks 24, 48, and 96
measure: Part 1: Time to First Relapse
timeFrame: Up to Week 96
measure: Part 1: Percentage of Participants Free of Relapse at Weeks 48 and 96
timeFrame: Weeks 48 and 96
measure: Part 1: Change from Baseline in Cognition at Weeks 24, 48, 72, and 96 as Measured by the Symbol Digit Modality Test (SDMT)
timeFrame: Baseline, Weeks 24, 48, 72, and 96
measure: Part 1: Change from Baseline in the Expanded Disability Status Scale (EDSS) Score at Weeks 48 and 96
timeFrame: Baseline, Weeks 48, and 96
measure: Part 1: 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
timeFrame: Baseline, Weeks 24, 48, 72 and 96
measure: Part 1: Area Under the Plasma Concentration-Time Curve from Time Zero to End of Dosing Interval (AUCtau) for BIIB017
timeFrame: 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
measure: Part 1: Maximum Observed Plasma Concentration (Cmax) at Steady State for BIIB017
timeFrame: 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
measure: Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) at Steady State for BIIB017
timeFrame: 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
measure: Part 1: Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Treatment Discontinuation
timeFrame: Up to Week 100
measure: Part 1: Change from Baseline in Height at Weeks 24, 48, 72, 96, and 100
timeFrame: Baseline, Weeks 24, 48, 72, 96, and 100
measure: Part 1: Change from Baseline in Weight at Weeks 24, 48, 72, 96, and 100
timeFrame: Baseline, Weeks 24, 48, 72, 96, and 100
measure: Part 1: Change from Baseline in Tanner Score at Weeks 24, 48, 72, 96, and 100
timeFrame: Baseline, Weeks 24, 48, 72, 96, and 100
measure: Part 1: Number of Participants With Binding and Neutralizing Antibodies to Interferon Beta Type 1a (IFN β-1a) [All Participants]
timeFrame: Up to Week 96
measure: Part 1: Number of Participants With Binding Antibodies to Peginterferon (PEG) [BIIB017-Treated Participants]
timeFrame: Up to Week 96
measure: Part 1: 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
timeFrame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, and 100
measure: Part 1: Change from Baseline in Blood Pressure at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
measure: Part 1: Change from Baseline in Pulse Rate at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
measure: Part 1: Change from Baseline in Body Temperature at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
measure: Part 1: Change from Baseline in Respiratory Rate at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
measure: Part 1: Change from Baseline in 12-Lead Electrocardiogram (ECG) Parameters at Weeks 48, 96, and 100
timeFrame: Baseline (Before dosing), Weeks 48, 96, and 100
measure: Part 1: Percentage of Participants with Changes Over Time in Clinical Laboratory Values
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
measure: Part 2: ARR at Weeks 144 and 192
timeFrame: Weeks 144 and 192
measure: Part 2: Change from Baseline in EDSS Score at Weeks 120, 144, 168, 192, and 196
timeFrame: Baseline (Week 96), Weeks 120, 144, 168, 192, and 196
measure: Part 2: Change from Baseline in Height at Weeks 120, 144, 168, 192, and 196
timeFrame: Baseline (Week 96), Weeks 120, 144, 168, 192, and 196
measure: Part 2: Change from Baseline in Weight at Weeks 120, 144, 168, 192, and 196
timeFrame: Baseline (Week 96), Weeks 120, 144, 168, 192, and 196
measure: Part 2: Change from Baseline in Tanner Score at Weeks 120, 144, 168, 192, and 196
timeFrame: Baseline (Week 96), Weeks 120, 144, 168, 192, and 196
measure: Part 2: Number of Participants With Binding and Neutralizing Antibodies to IFN β-1a (All Participants)
timeFrame: Up to Week 192
measure: Part 2: Number of Participants With Binding Antibodies to PEG (BIIB017-Treated Participants)
timeFrame: Up to Week 192
measure: Part 2: Change from Baseline in Blood Pressure at Weeks 120,144,168, 192, and 196
timeFrame: Baseline (Week 96), Weeks 120, 144, 168, 192, and 196
measure: Part 2: Change from Baseline in Pulse Rate at Weeks 120, 144, 168, 192, and 196
timeFrame: Baseline (Week 96), Weeks 120, 144, 168, 192, and 196
measure: Part 2: Change from Baseline in Body Temperature at Weeks 120, 144, 168, 192, and 196
timeFrame: Baseline (Week 96), Weeks 120, 144, 168, 192, and 196
measure: Part 2: Change from Baseline in Respiratory Rate at Weeks 120, 144, 168, 192, and 196
timeFrame: Baseline (Week 96), Weeks 120, 144, 168, 192, and 196
measure: Part 2: Change from Baseline in 12-Lead ECG Parameters at Weeks 144, 192, and 196
timeFrame: Baseline (Week 96), Weeks 144, 192, and 196
measure: 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
timeFrame: Baseline (Week 96), Weeks 108, 120, 132, 144,156, 168, 180, 192, and 196
measure: Part 2: Percentage of Participants with Changes Over Time in Clinical Laboratory Values
timeFrame: Baseline (Week 96), Weeks 108, 120, 132, 144, 156, 168, 180, 192, and 196
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Health
state: California
city: Chapel Hill
country: United States
facility: UNC Hospitals
state: North Carolina
city: Norfolk
country: United States
facility: Meridian Clinical Research
state: Virginia
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
state: Buenos Aires
city: Parkville
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Ghent
state: East Flanders
city: Liege
country: Belgium
facility: Clinique CHC MontLégia
state: Wallonia
city: Sofia
country: Bulgaria
facility: MHATNP 'Sv.Naum', EAD
city: Split
country: Croatia
facility: University Hospital Centre Split
state: Dalmatia
city: Zagreb
country: Croatia
facility: Children's Hospital Zagreb
city: Zagreb
country: Croatia
facility: Clinical Hospital Center 'Sestre Milosrdnice'
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Strasbourg
country: France
facility: CHU Strasbourg - Hôpital Hautepierre
state: Bas Rhin
city: Toulouse cedex 9
country: France
facility: Hopital Purpan
state: Haute Garonne
city: Montpellier
country: France
facility: Hopital Gui de Chauliac
state: Herault
city: Lille Cedex
country: France
facility: Hopital Roger Salengro - CHU Lille
state: Nord
city: Le Kremlin Bicêtre cedex
country: France
facility: Hôpital Bicêtre
state: Val De Marne
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
state: Baden Wuerttemberg
city: Gottingen
country: Germany
facility: Universitaetsmedizin Goettingen
state: Niedersachsen
city: Bochum
country: Germany
facility: St. Josef-Hospital Universitaetsklinikum
state: Nordrhein Westfalen
city: Berlin
country: Germany
facility: Charité - Campus Virchow-Klinikum
city: Larissa
country: Greece
facility: General Hospital of Larissa
state: Thessaly
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki 'Hippokration'
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem KK
state: Baranya
city: Debrecen
country: Hungary
facility: Debreceni Egyetem
state: Hajdú-Bihar
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Jerusalem
country: Israel
facility: Hadassah University Hospital - Ein Kerem
state: Levant
city: Petach-Tikva
country: Israel
facility: Schneider Children's Medical Center
state: Tel Aviv
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria 'Federico II'
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria- Università degli Studi della Campania "Luigi Vanvitelli"
city: Shuwaikh
country: Kuwait
facility: Ibn Sina Hospital
city: Lisboa
country: Portugal
facility: Centro Hospitalar e Universitário Lisboa Norte E.P.E.
state: Lisbon
city: Loures
country: Portugal
facility: Hospital Beatriz Ângelo
state: Lisbon
city: Braga
country: Portugal
facility: Hospital de Braga
state: Minho
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitário de Coimbra E.P.E. - Hospital Pediátrico
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto, E.P.E. - Hospital de Santo António
city: Ufa
country: Russian Federation
facility: SBEI HPE 'Bashkir State Medical University' of the MoH of the RF
state: Bashkortostan
city: Krasnoyarsk
country: Russian Federation
facility: FSBI "Federal Siberian Scientific-Clinical Center of FMBA"
state: Krasnoyarsk Krai
city: St. Petersburg
country: Russian Federation
facility: LLC National center for socially significan disease
state: Leningrad
city: Tomsk
country: Russian Federation
facility: Nebbiolo LLC
state: Oblast
city: Kemerovo
country: Russian Federation
facility: SAIH 'Kemerovo Regional Clinical Hospital'
state: Siberia
city: Belgorod
country: Russian Federation
facility: RSBIH 'Belgorod Regional Clinical Hospital of Saint Ioasaf'
city: Moscow
country: Russian Federation
facility: SBHI
city: Moscow
country: Russian Federation
facility: SBIH of Moscow region "Moscow Regional Scientific & Research
city: Rostov-on-Don
country: Russian Federation
facility: SBEI HPE 'Rostov State Medical University' of the MoH of the RF
city: Yaroslavl
country: Russian Federation
facility: State Budgetary Institution of Healthcare of Yaroslavl region 'Clinical Hospital # 2'
city: Jeddah
country: Saudi Arabia
facility: King Faisal Specialist Hospital & Research Center
state: Makkah
city: Riyadh
country: Saudi Arabia
facility: King Saud University
city: Belgrade
country: Serbia
facility: Clinic of Neurology and Psychiatry for Children and Youth
state: Balkans
city: Belgrade
country: Serbia
facility: University Children Hospital
state: Balkans
city: Belgrade
country: Serbia
facility: Mother and Child Health Care Institute of Serbia ,,Dr Vukan Cupic''
state: Balkans
city: Bratislava
country: Slovakia
facility: Narodny ustav detskych chorob
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu
state: Barcelona
city: El Palmar
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
state: Murcia
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Manouba
country: Tunisia
facility: Hopital Razi
state: Mannouba
city: Monastir
country: Tunisia
facility: Hôpital Fattouma Bourghiba
city: Sfax
country: Tunisia
facility: Hôpital Habib Bourguiba
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty Clinical Research Unit
city: Antalya
country: Turkey
facility: Akdeniz University Medical Faculty
city: Izmir
country: Turkey
facility: Izmir Dr. Behcet Uz Cocuk Hastaliklari ve Cerrahisi Egitim ve Arastirma Hastanesi
city: Samsun
country: Turkey
facility: Ondokuz Mayis Univ. Med. Fac.
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: