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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03958877
Recruitment Status : Recruiting
First Posted : May 22, 2019
Last Update Posted : March 26, 2020
Sponsor:
Information provided by (Responsible Party):
Biogen

Tracking Information
First Submitted Date  ICMJE May 20, 2019
First Posted Date  ICMJE May 22, 2019
Last Update Posted Date March 26, 2020
Actual Study Start Date  ICMJE October 18, 2019
Estimated Primary Completion Date March 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 20, 2019)
  • Part 1: Annualized Relapse Rate (ARR) at Week 96 [ Time Frame: Week 96 ]
    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.
  • Part 2: Percentage of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Study Treatment Discontinuation [ Time Frame: From Week 96 to Week 196 ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2019)
  • Part 1: ARR at Week 48 [ Time Frame: Week 48 ]
    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.
  • 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 Up to Week 96 [ Time Frame: Up to Week 96 ]
  • Part 1: Change from Baseline in Cognition at Weeks 24, 48, 72 and 96 as Measured by the Symbol Digit Modality Test (SDMT) [ Time Frame: Baseline, Weeks 24, 48, 72 and 96 ]
    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.
  • Part 1: Change from Baseline in the Expanded Disability Status Scale (EDSS) Score at Weeks 48 and 96 [ Time Frame: Baseline, 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).
  • 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, 96 and 100 [ Time Frame: Baseline, Weeks 24, 48, 72, 96 and 100 ]
    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.
  • 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 ]
    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.
  • 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 [ Time Frame: Baseline, 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.
  • Part 1: Number of Participants With Binding and Neutralizing Antibodies to Interferon Beta Type 1a (IFN β-1a) [All Participants] [ Time Frame: Up to Week 96 ]
    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.
  • Part 1: Number of Participants With Binding Antibodies to Peginterferon (PEG) [BIIB017-Treated Participants] [ Time Frame: Up to Week 96 ]
    Anti-PEG binding antibodies in human serum will be determined using an ELISA.
  • 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 [ Time Frame: Baseline, 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.
  • 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 Heart 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 [ Time Frame: Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96 and 100 ]
    Clinical laboratory tests include: hematology, chemistry (including liver, renal and thyroid function), and coagulation tests.
  • Part 2: ARR at Weeks 144 and 192 [ Time Frame: Weeks 144 and 192 ]
    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.
  • Part 2: Change from Baseline in EDSS Score at Weeks 120, 144, 168, 192 and 196 [ Time Frame: Baseline (Week 96), 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).
  • 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 [ Time Frame: Baseline (Week 96), 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.
  • Part 2: Number of Participants With Binding and Neutralizing Antibodies to IFN β-1a (All Participants) [ Time Frame: Up to Week 192 ]
    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.
  • Part 2: Number of Participants With Binding Antibodies to PEG (BIIB017-Treated Participants) [ Time Frame: Up to Week 192 ]
    Anti-PEG binding antibodies in human serum will be determined using an ELISA.
  • 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 Heart 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 [ Time Frame: Baseline (Week 96), 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.
  • Part 2: Percentage of Participants with Changes Over Time in Clinical Laboratory Values [ Time Frame: Baseline (Week 96), Weeks 108, 120, 132, 144, 156, 168, 180, 192 and 196 ]
    Clinical laboratory tests include: hematology, chemistry (including liver, renal and thyroid function), and coagulation tests.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis, Relapsing-Remitting
Intervention  ICMJE
  • Drug: BIIB017 (peginterferon beta-1a)
    Administered as specified in the treatment arm
    Other Name: PLEGRIDY
  • Drug: Interferon beta type 1a
    Administered as specified in the treatment arm
    Other Name: Avonex
Study Arms  ICMJE
  • Experimental: BIIB017 (peginterferon beta-1a)
    Participants will receive subcutaneous (SC) injection of BIIB017 (peginterferon beta-1a) 63 microgram (μg) on Day 1, followed by 94 μg at Week 2, followed by 125 μg at Week 4, and then 125 μg SC injection every 2 weeks up to Week 96 in Part 1 of the study. Participants who enter optional Part 2 of the study will receive 125 μg SC injections of BIIB017 every 2 weeks for 96 Weeks.
    Intervention: Drug: BIIB017 (peginterferon beta-1a)
  • Active Comparator: Avonex
    Participants will receive Avonex (interferon beta type 1a) starting at a dose of 7.5 μg on Day 1, followed by an increase of 7.5 μg each week for 3 weeks, followed by 30 μg intramuscular (IM) injections every week up to Week 96 in Part 1 of the study. Participants who enter optional Part 2 of the study will receive 125 μg SC injections of BIIB017 every 2 weeks for 96 Weeks.
    Intervention: Drug: Interferon beta type 1a
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 20, 2019)
142
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2023
Estimated Primary Completion Date March 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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"

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 10 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US Biogen Clinical Trial Center 866-633-4636 clinicaltrials@biogen.com
Contact: Global Biogen Clinical Trial Center clinicaltrials@biogen.com
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Bulgaria,   Croatia,   Czechia,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Kuwait,   Portugal,   Russian Federation,   Saudi Arabia,   Serbia,   Slovakia,   Spain,   Tunisia,   Turkey,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03958877
Other Study ID Numbers  ICMJE 105MS306
2018-003008-38 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on http://clinicalresearch.biogen.com/
URL: http://www.biogenclinicaldatarequest.com
Responsible Party Biogen
Study Sponsor  ICMJE Biogen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Biogen
PRS Account Biogen
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP