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

Phase 3Active Not RecruitingNCT03958877

Biogen152 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

152

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

BIIB017 (peginterferon beta-1a)

Eligibility

Sex: ALLMin age: 10 YearsMax age: 18 Years

Medical Language ↔ Plain English

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 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 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.

Locations (65)

UC San Diego Health

La Jolla, California, United States

UNC Hospitals

Chapel Hill, North Carolina, United States

Meridian Clinical Research

Norfolk, Virginia, United States

Hospital Italiano de Buenos Aires

Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina

Royal Children's Hospital

Parkville, Victoria, Australia

Outcomes

Primary Outcomes

Part 1: Annualized Relapse Rate (ARR) at Week 48

A multiple sclerosis (MS) relapse is defined as the onset of new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings. ARR is calculated as the total number of relapses in each treatment group adjusted for the duration of study treatment in person-years.

Time frame: Week 48

Part 2: Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Treatment Discontinuation

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, or is a medically important event.

Time frame: From Week 96 to Week 196

Secondary Outcomes

Part 1: ARR at Week 96

An MS relapse is defined as the onset of new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings. ARR is calculated as the total number of relapses in each treatment group adjusted for the duration of study treatment in person-years.

Time frame: Week 96

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

Time frame: Weeks 24, 48, and 96

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

Time frame: Weeks 24, 48, and 96

Part 1: Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans at Weeks 24, 48, and 96

Time frame: Weeks 24, 48, and 96

Part 1: Number of Gd-Enhancing Lesions on Brain MRI Scans at Weeks 24, 48, and 96

Time frame: Weeks 24, 48, and 96

Part 1: Time to First Relapse

Time frame: Up to Week 96

Part 1: Percentage of Participants Free of Relapse at Weeks 48 and 96

Time frame: Weeks 48 and 96

Part 1: Change from Baseline in Cognition at Weeks 24, 48, 72, and 96 as Measured by the Symbol Digit Modality Test (SDMT)

The SDMT measures the time to pair abstract symbols with specific numbers. The test requires elements of attention, visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items from 0 (worst) to 110 (best) in 90 seconds. The total score provides a measure of the speed and accuracy of symbol-digit substitution. Higher scores indicate better performance.

Time frame: Baseline, Weeks 24, 48, 72, and 96

Part 1: Change from Baseline in the Expanded Disability Status Scale (EDSS) Score at Weeks 48 and 96

EDSS is based on a standardized neurological exam and focuses on symptoms that commonly occur in MS. Scores range from 0.0 (normal) to 10.0 (death due to MS).

Time frame: Baseline, Weeks 48, and 96

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

The PedsQL consists of 23 items in four generic score scales: physical functioning, emotional functioning, social functioning, and school functioning that measures health related quality of life. The questionnaire asks how much of a problem each item has been during the past month. Each item is answered on a scale of 0 (never) to 4 (almost always) then the scores are transformed to a 0 to 100 scale, so that higher scores indicate better heath related quality of life.

Time frame: Baseline, Weeks 24, 48, 72 and 96

Part 1: 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

Part 1: Maximum Observed Plasma Concentration (Cmax) at Steady State 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

Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) at Steady State 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

Part 1: Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Treatment Discontinuation

Time frame: Up to Week 100

Part 1: Change from Baseline in Height at Weeks 24, 48, 72, 96, and 100

Time frame: Baseline, Weeks 24, 48, 72, 96, and 100

Part 1: Change from Baseline in Weight at Weeks 24, 48, 72, 96, and 100

Time frame: Baseline, Weeks 24, 48, 72, 96, and 100

Part 1: Change from Baseline in Tanner Score at Weeks 24, 48, 72, 96, and 100

Assessment of Tanner stages (a scale of physical development) will be performed by a medical doctor experienced with this assessment. Tanner score ranges from Stage 1 (childhood) to Stage 5 (full physical maturity). Information regarding Tanner staging will be collected for all male participants with bone age less than (\<) 16 years and for female participants who are pre-menarche and have a bone age \< 16 years and will be stopped once the participant's bone age reaches greater than or equal to (\>=) 16 years or (once the participant is post-menarche. Tanner Score can be omitted if required by country-specific regulations and/or local ethics committees.

Time frame: Baseline, Weeks 24, 48, 72, 96, and 100

Part 1: Number of Participants With Binding and Neutralizing Antibodies to Interferon Beta Type 1a (IFN β-1a) [All Participants]

Presence of IFN β-1a antibodies in human serum will be determined using enzyme-linked immunosorbent assay (ELISA) followed by further characterization and titration of positive samples in a cell-based neutralizing antibody assay.

Time frame: Up to Week 96

Part 1: 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.

Time frame: Up to Week 96

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

MINI-KID is a short (approximately 15 minute) structured diagnostic interview used to assess the presence of 20 diagnostic and statistical manual of mental disorders, 4th Edition (DSM-IV) child and adolescent psychiatric disorders as well as the risk of suicide. The MINI-Kid frames questions in language that is easy for children and adolescents. It consists of 137 questions across 24 modules.

Time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, and 100

Part 1: Change from Baseline in Blood Pressure at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100

Time frame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100

Part 1: Change from Baseline in Pulse Rate at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100

Time frame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100

Part 1: Change from Baseline in Body Temperature at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100

Time frame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100

Part 1: Change from Baseline in Respiratory Rate at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100

Time frame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100

Part 1: Change from Baseline in 12-Lead Electrocardiogram (ECG) Parameters at Weeks 48, 96, and 100

Time frame: Baseline (Before dosing), Weeks 48, 96, and 100

Part 1: 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.

Time frame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100

Part 2: ARR at Weeks 144 and 192

Time frame: Weeks 144 and 192

Part 2: Change from Baseline in EDSS Score at Weeks 120, 144, 168, 192, and 196

EDSS is based on a standardized neurological exam and focuses on symptoms that commonly occur in MS. Scores range from 0.0 (normal) to 10.0 (death due to MS).

Time frame: Baseline (Week 96), Weeks 120, 144, 168, 192, and 196

Part 2: Change from Baseline in Height at Weeks 120, 144, 168, 192, and 196

Time frame: Baseline (Week 96), Weeks 120, 144, 168, 192, and 196

Part 2: Change from Baseline in Weight at Weeks 120, 144, 168, 192, and 196

Time frame: Baseline (Week 96), Weeks 120, 144, 168, 192, and 196

Part 2: Change from Baseline in Tanner Score at Weeks 120, 144, 168, 192, and 196

Assessment of Tanner stages (a scale of physical development) will be performed by a medical doctor experienced with this assessment. Tanner score ranges from Stage 1 (childhood) to Stage 5 (full physical maturity). Information regarding Tanner staging will be collected for all male participants with bone age \< 16 years and for female participants who are pre-menarche and have a bone age \<16 years and will be stopped once the participant's bone age reaches \>= 16 years or (once the participant is post-menarche. Tanner Score can be omitted if required by country-specific regulations and/or local ethics committees.

Time frame: Baseline (Week 96), Weeks 120, 144, 168, 192, and 196

Part 2: Number of Participants With Binding and Neutralizing Antibodies to IFN β-1a (All Participants)

Presence of IFN β-1a antibodies in human serum will be determined using ELISA followed by further characterization and titration of positive samples in a cell-based neutralizing antibody assay.

Time frame: Up to Week 192

Part 2: Number of Participants With Binding Antibodies to PEG (BIIB017-Treated Participants)

Anti-PEG binding antibodies in human serum will be determined using an ELISA.

Time frame: Up to Week 192

Part 2: Change from Baseline in Blood Pressure at Weeks 120,144,168, 192, and 196

Time frame: Baseline (Week 96), Weeks 120, 144, 168, 192, and 196

Part 2: Change from Baseline in Pulse Rate at Weeks 120, 144, 168, 192, and 196

Time frame: Baseline (Week 96), Weeks 120, 144, 168, 192, and 196

Part 2: Change from Baseline in Body Temperature at Weeks 120, 144, 168, 192, and 196

Time frame: Baseline (Week 96), Weeks 120, 144, 168, 192, and 196

Part 2: Change from Baseline in Respiratory Rate at Weeks 120, 144, 168, 192, and 196

Time frame: Baseline (Week 96), Weeks 120, 144, 168, 192, and 196

Part 2: Change from Baseline in 12-Lead ECG Parameters at Weeks 144, 192, and 196

Time frame: Baseline (Week 96), Weeks 144, 192, and 196

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

MINI-KID is a structured diagnostic interview instrument for psychiatric evaluation and outcome tracking. All questions are answered Yes or No.

Time frame: Baseline (Week 96), Weeks 108, 120, 132, 144,156, 168, 180, 192, and 196

Part 2: 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.

Time frame: Baseline (Week 96), Weeks 108, 120, 132, 144, 156, 168, 180, 192, and 196