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

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03958877
• Other study ID #: 105MS306
• Secondary ID: 2018-003008-3820
• Status: Recruiting
• Phase: Phase 3
• Start date: October 18, 2019
• Est. completion date: November 5, 2029

Study information

• Verified date: January 2024
• Source: Biogen
• Contact: US Biogen Clinical Trial Center
• Phone: 866-633-4636
• Email: clinicaltrials[@]biogen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 142
• Est. completion date: November 5, 2029
• Est. primary completion date: November 5, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 18 Years

Eligibility

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 ß-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"

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• BIIB017 (peginterferon beta-1a)
Administered as specified in the treatment arm
• Interferon beta type 1a
Administered as specified in the treatment arm

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autonoma de Buenos Aires	Buenos Aires
Australia	Royal Children's Hospital	Parkville	Victoria
Belgium	Universitair Ziekenhuis Gent	Gent	East Flanders
Belgium	Clinique CHC MontLégia	Liege	Wallonia
Bulgaria	MHATNP "Sv.Naum", EAD	Sofia
Croatia	University Hospital Centre Split	Split	Dalmatia
Croatia	Children's Hospital Zagreb	Zagreb
Croatia	Clinical Hospital 'Sestre Milosrdnice'	Zagreb
Croatia	University Hospital Centre Zagreb	Zagreb
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
France	Hôpital Bicêtre	Le Kremlin Bicêtre cedex	Val De Marne
France	Hopital Roger Salengro - CHU Lille	Lille	Nord
France	Hopital Gui de Chauliac	Montpellier	Herault
France	CHU Strasbourg - Hôpital Hautepierre	Strasbourg	Bas Rhin
France	Hopital Purpan	Toulouse cedex 9	Haute Garonne
Germany	Charité - Campus Virchow-Klinikum	Berlin
Germany	St. Josef-Hospital Universitaetsklinikum	Bochum	Nordrhein Westfalen
Germany	Universitaetsklinikum Freiburg	Freiburg	Baden Wuerttemberg
Germany	Universitaetsmedizin Goettingen	Gottingen	Niedersachsen
Greece	General Hospital of Larissa	Larissa	Thessaly
Greece	IASO Children's Hospital	Marousi
Greece	General Hospital of Thessaloniki 'Hippokration'	Thessaloniki
Hungary	Semmelweis Egyetem AOK	Budapest
Hungary	Debreceni Egyetem	Debrecen	Hajdú-Bihar
Hungary	Pecsi Tudomanyegyetem	Pecs	Baranya
Israel	Hadassah University Hospital - Ein Kerem	Jerusalem	Levant
Israel	Schneider Children's Medical Center	Petach-Tikva	Tel Aviv
Italy	Azienda Ospedaliero Universitaria Ospedale Pediatrico Meyer	Firenze
Italy	Azienda Ospedaliera Universitaria 'Federico II'	Napoli
Italy	Azienda Ospedaliera Universitaria- Università degli Studi della Campania "Luigi Vanvitelli"	Napoli	Campania
Kuwait	Ibn Sina Hospital	Shuwaikh
Portugal	Hospital de Braga	Braga	Minho
Portugal	Centro Hospitalar e Universitário de Coimbra E.P.E. - Hospital Pediátrico	Coimbra
Portugal	Centro Hospitalar e Universitário Lisboa Norte E.P.E.	Lisboa	Lisbon
Portugal	Hospital Beatriz Ângelo	Loures	Lisbon
Portugal	Centro Hospitalar do Porto, E.P.E. - Hospital de Santo António	Porto
Russian Federation	RSBIH 'Belgorod Regional Clinical Hospital of Saint Ioasaf'	Belgorod
Russian Federation	SAIH 'Kemerovo Regional Clinical Hospital'	Kemerovo	Siberia
Russian Federation	FSBI "Federal Siberian Scientific-Clinical Center of FMBA"	Krasnoyarsk	Krasnoyarsk Krai
Russian Federation	SBHI	Moscow
Russian Federation	SBIH of Moscow region "Moscow Regional Scientific & Research	Moscow
Russian Federation	SBEI HPE 'Rostov State Medical University' of the MoH of the RF	Rostov-on-Don
Russian Federation	LLC National center for socially significan disease	St. Petersburg	Leningrad
Russian Federation	Nebbiolo LLC	Tomsk	Oblast
Russian Federation	SBEI HPE 'Bashkir State Medical University' of the MoH of the RF	Ufa	Bashkortostan
Russian Federation	State Budgetary Institution of Healthcare of Yaroslavl region 'Clinical Hospital # 2'	Yaroslavl
Saudi Arabia	King Faisal Specialist Hospital & Research Center	Jeddah	Makkah
Saudi Arabia	King Saud University	Riyadh
Serbia	Clinic of Neurology and Psychiatry for Children and Youth	Belgrade	Balkans
Serbia	Mother and Child Health Care Institute of Serbia ''Dr Vukan Cupic''	Belgrade	Balkans
Serbia	University Children's Hospital	Belgrade	Balkans
Slovakia	Narodny ustav detskych chorob	Bratislava
Spain	Hospital Universitario Reina Sofia	Cordoba
Spain	Hospital Universitario Virgen de la Arrixaca	El Palmar	Murcia
Spain	Hospital Sant Joan de Deu	Esplugues de Llobregat	Barcelona
Spain	Hospital Universitario Ramon y Cajal	Madrid
Tunisia	Hopital Razi	Manouba	Mannouba
Tunisia	Hôpital Fattouma Bourghiba	Monastir
Tunisia	Hôpital Habib Bourguiba	Sfax
Turkey	Gazi University Medical Faculty Clinical Research Unit	Ankara
Turkey	Akdeniz University Medical Faculty	Antalya
Turkey	Izmir Dr. Behcet Uz Cocuk Hastaliklari ve Cerrahisi Egitim ve Arastirma Hastanesi	Izmir
Turkey	Ondokuz Mayis Univ. Med. Fac.	Samsun
United States	UNC Hospitals	Chapel Hill	North Carolina
United States	Meridian Clinical Research	Norfolk	Virginia
United States	UC San Diego Health	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Bulgaria,  Croatia,  Czechia,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Kuwait,  Portugal,  Russian Federation,  Saudi Arabia,  Serbia,  Slovakia,  Spain,  Tunisia,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Week 48
Primary	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.	From Week 96 to Week 196
Secondary	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.	Week 96
Secondary	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		Weeks 24, 48, and 96
Secondary	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		Weeks 24, 48, and 96
Secondary	Part 1: Number of New or Newly Enlarging T2 Hyperintense Lesions on Brain MRI Scans at Weeks 24, 48, and 96		Weeks 24, 48, and 96
Secondary	Part 1: Number of Gd-Enhancing Lesions on Brain MRI Scans at Weeks 24, 48, and 96		Weeks 24, 48, and 96
Secondary	Part 1: Time to First Relapse		Up to Week 96
Secondary	Part 1: Percentage of Participants Free of Relapse at Weeks 48 and 96		Weeks 48 and 96
Secondary	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.	Baseline, Weeks 24, 48, 72, and 96
Secondary	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).	Baseline, Weeks 48, and 96
Secondary	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.	Baseline, Weeks 24, 48, 72 and 96
Secondary	Part 1: Area Under the Plasma Concentration-Time Curve from Time Zero to End of Dosing Interval (AUCtau) 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
Secondary	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
Secondary	Part 1: 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
Secondary	Part 1: 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.	Up to Week 100
Secondary	Part 1: Change from Baseline in Height at Weeks 24, 48, 72, 96, and 100		Baseline, Weeks 24, 48, 72, 96, and 100
Secondary	Part 1: Change from Baseline in Weight at Weeks 24, 48, 72, 96, and 100		Baseline, Weeks 24, 48, 72, 96, and 100
Secondary	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.	Baseline, Weeks 24, 48, 72, 96, and 100
Secondary	Part 1: Number of Participants With Binding and Neutralizing Antibodies to Interferon Beta Type 1a (IFN ß-1a) [All Participants]	Presence of IFN ß-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.	Up to Week 96
Secondary	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.	Up to Week 96
Secondary	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.	Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, and 100
Secondary	Part 1: Change from Baseline in Blood Pressure at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100		Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
Secondary	Part 1: Change from Baseline in Pulse Rate at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100		Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
Secondary	Part 1: Change from Baseline in Body Temperature at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100		Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
Secondary	Part 1: Change from Baseline in Respiratory Rate at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100		Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
Secondary	Part 1: Change from Baseline in 12-Lead Electrocardiogram (ECG) Parameters at Weeks 48, 96, and 100		Baseline (Before dosing), Weeks 48, 96, and 100
Secondary	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.	Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, and 100
Secondary	Part 2: ARR at 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.	Weeks 144 and 192
Secondary	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).	Baseline (Week 96), Weeks 120, 144, 168, 192, and 196
Secondary	Part 2: Change from Baseline in Height at Weeks 120, 144, 168, 192, and 196		Baseline (Week 96), Weeks 120, 144, 168, 192, and 196
Secondary	Part 2: Change from Baseline in Weight at Weeks 120, 144, 168, 192, and 196		Baseline (Week 96), Weeks 120, 144, 168, 192, and 196
Secondary	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.	Baseline (Week 96), Weeks 120, 144, 168, 192, and 196
Secondary	Part 2: Number of Participants With Binding and Neutralizing Antibodies to IFN ß-1a (All Participants)	Presence of IFN ß-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.	Up to Week 192
Secondary	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.	Up to Week 192
Secondary	Part 2: Change from Baseline in Blood Pressure at Weeks 120,144,168, 192, and 196		Baseline (Week 96), Weeks 120, 144, 168, 192, and 196
Secondary	Part 2: Change from Baseline in Pulse Rate at Weeks 120, 144, 168, 192, and 196		Baseline (Week 96), Weeks 120, 144, 168, 192, and 196
Secondary	Part 2: Change from Baseline in Body Temperature at Weeks 120, 144, 168, 192, and 196		Baseline (Week 96), Weeks 120, 144, 168, 192, and 196
Secondary	Part 2: Change from Baseline in Respiratory Rate at Weeks 120, 144, 168, 192, and 196		Baseline (Week 96), Weeks 120, 144, 168, 192, and 196
Secondary	Part 2: Change from Baseline in 12-Lead ECG Parameters at Weeks 144, 192, and 196		Baseline (Week 96), Weeks 144, 192, and 196
Secondary	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.	Baseline (Week 96), Weeks 108, 120, 132, 144,156, 168, 180, 192, and 196
Secondary	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.	Baseline (Week 96), Weeks 108, 120, 132, 144, 156, 168, 180, 192, and 196