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    Summary
    EudraCT Number:2020-000207-36
    Sponsor's Protocol Code Number:275AS101
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2020-12-04
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2020-000207-36
    A.3Full title of the trial
    A Phase 1/2 Multiple-Ascending-Dose Study With a Long-Term Open-Label
    Extension to Assess the Safety, Tolerability, Pharmacokinetics,
    Pharmacodynamics, and Effect on Disease Progression of BIIB105
    Administered Intrathecally to Adults With Amyotrophic Lateral Sclerosis
    With or Without Poly-CAG Expansion in the Ataxin-2 Gene
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Assess the Safety, Tolerability, Pharmacokinetics,
    Pharmacodynamics, and Effect on Disease Progression of BIIB105 in
    Participants With Amyotrophic Lateral Sclerosis With or Without Polycytosine- adenine-guanine (CAG) Expansion in the Ataxin-2 Gene
    A.3.2Name or abbreviated title of the trial where available
    ALSpire
    A.4.1Sponsor's protocol code number275AS101
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorBiogen Idec Research Limited
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportBiogen Idec Research Limited
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBiogen
    B.5.2Functional name of contact pointMedical Director/Monitor
    B.5.3 Address:
    B.5.3.1Street AddressInnovation house, 70 Norden Road
    B.5.3.2Town/ cityMaidenhead
    B.5.3.3Post codeSL6 4AY
    B.5.3.4CountryUnited Kingdom
    B.5.6E-mailclinicialTrials@biogen.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code BIIB105
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntrathecal use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBIIB105
    D.3.9.2Current sponsor codeBIIB105
    D.3.9.3Other descriptive nameBIIB105
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboIntrathecal use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    ALS and ALS associated with ataxin-2 (ATXN2) poly-CAG expansion (polyQ-ALS)
    E.1.1.1Medical condition in easily understood language
    Amyotrophic Lateral Sclerosis
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10002026
    E.1.2Term Amyotrophic lateral sclerosis
    E.1.2System Organ Class 10029205 - Nervous system disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10052653
    E.1.2Term Amyotrophic lateral sclerosis gene carrier
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Part 1: The primary objective is to evaluate the safety and tolerability of
    BIIB105 in participants with amyotrophic lateral sclerosis (ALS) or poly-
    CAG expansion (polyQ)-ALS.
    Part 2: The primary objective is to evaluate the long-term safety and
    tolerability of BIIB105 in participants with ALS or polyQ-ALS.
    Parts 1 and 2: The primary objective is to evaluate the long-term safety
    and tolerability of BIIB105 in participants with ALS or polyQ-ALS.
    E.2.2Secondary objectives of the trial
    Part 1: The secondary objectives are to assess the pharmacokinetic (PK)
    profile in serum and cerebrospinal fluid (CSF), and to evaluate the
    biomarker effect of BIIB105 in participants with ALS or polyQ-ALS.
    Parts 1 and 2: The secondary objectives are to assess the long-term PK
    profile of BIIB105 in serum and CSF of participants with ALS or polyQALS;
    to evaluate the long-term biomarker effect of BIIB105 in
    participants with ALS or polyQ-ALS; to assess the impact of earlier
    initiation of BIIB105 (i.e., at start of Part 1) compared with delayed
    initiation of BIIB105 (i.e., at start of Part 2) on biomarkers; to evaluate
    the long-term effect of BIIB105 on measures of clinical function and to
    assess the impact of earlier initiation of BIIB105 (i.e., at start of Part 1)
    compared with delayed initiation of BIIB105 (i.e., at start of Part 2) on
    measures of clinical function.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Key Inclusion Criteria:
    Part 1:
    - Ability of the participant to understand the purpose and risks of the
    study and indicate informed consent, and the ability of the participant or the participant's legally authorized representative to provide signed and dated informed consent and authorization to use protected health
    information in accordance with national and local privacy regulations.
    - All women of childbearing potential and all men must ensure that highly effective contraception is used during the study and for at least 6 months for female participants and 8 months for male participants after their last dose of study treatment.
    - No known presence or family history of mutations in the the
    superoxide dismutase 1 (SOD1) or fused in sarcoma (FUS) genes.
    - Participants in Cohorts A, B, C1 and D1, must meet the laboratory-supported probable, probable, or definite criteria for diagnosing ALS according to the World Federation of Neurology El Escorial criteria (revised according to the Airlie House Conference 1998 [Brooks
    2000]). Participants in Cohort C2 and D2, must meet any of the prior conditions, but may also only meet clinically possible criteria for diagnosing ALS, or exhibit weakness attributable to ALS in the presence of ataxin-2 protein (ATXN2) intermediate repeats.
    - In participants in Cohorts C2 and D2, confirmed intermediate cytosine-adenine-guanine/cytosineadenine-adenine (CAG/CAA) repeat expansion in the ataxin-2 gene or RNA (ATXN2) gene as defined by at least 1 allele carrying 30 to 33 CAG/CAA repeats.
    - No known presence or family history of mutations in the SOD1 or FUS genes.
    - Slow vital capacity (SVC) criteria:
    - In participants in Cohorts A, B, C1, and D1, SVC ≥60% of predicted value as adjusted for sex, age, and height (from the sitting position).
    - In participants in Cohorts C2 and D2, SVC ≥50% of predicted value as adjusted for sex, age, and height (from the sitting position).
    - If taking riluzole, participant must be on a stable dose for ≥30 days prior to Day 1 and expected to remain at that dose until the final study visit, unless the Investigator determines that it should be discontinued for medical reasons, in which case it may not be restarted during the study.
    - Participants taking concomitant edaravone at study entry must be on a stable dose for ≥60 days prior to the first dose of study treatment (Day 1).
    - Participants taking concomitant edaravone must be willing to continue with the same dose regimen throughout the study, unless the Investigator determines that edaravone should be discontinued for medical reasons, in which case it may not be restarted during the study. Edaravone may not be administered on dosing days of this study.
    - Screening values of coagulation parameters including platelet count, international normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) should be within normal ranges.
    - Has an informant/caregiver who, in the Investigator’s judgment, has frequent and sufficient contact with the participant as to be able to provide accurate information about the participant’s cognitive and functional abilities at screening.

    Part 2:
    -Ability of the participant to understand the purpose and risks of the study and indicate informed consent, and the ability of the participant or the participant's legally authorized representative to provide signed and dated informed consent and authorization to use protected health information in accordance with national and local privacy regulations
    - Participants must have completed Study 275AS101 Part 1 through Week 25 (Day 175 Visit for Cohorts A, B, C1, C2; Day 176 Visit for
    Cohorts D1, D2).
    - Participants from Cohorts A, B, C1, and C2 must have a washout of ≥16 weeks between the last dose of study treatment received in study
    275AS101 Part 1 and the first dose of BIIB105 received in Study
    275AS101 Part 2. Participants from Cohorts D1 and D2 do not require a washout period.
    - If taking riluzole, participant must be on a stable dose for ≥ 30 days
    prior to Day 1 and expected to remain at that dose until the final study visit, unless the Investigator determines that it should be discontinued for medical reasons, in which case it may not be restarted during the study.
    - Participants taking concomitant edaravone at study entry must be on a stable dose for ≥ 60 days prior to the first dose of study treatment (Day 1).
    - Screening values of coagulation parameters including platelet count,
    INR, PT, and aPTT should be within normal ranges.

    NOTE: Other protocol defined Inclusion criteria may apply.
    E.4Principal exclusion criteria
    Key Exclusion Criteria:
    Part 1:
    - History or positive test result at Screening for HIV.
    - Current hepatitis C infection.
    - Current hepatitis B infection.
    - History of alcohol or substance abuse ≤6 months of Screening that would limit participation in the study, as determined by the Investigator.
    - Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system during the study period.
    - Presence of tracheostomy.
    - In participants from Cohorts A, B, C1, and D1, history of myocardial infarction, as determined by the Investigator.
    - In participants from Cohorts A, B, C1, and D1, poorly controlled type 1 or 2 diabetes mellitus defined as HbA1c ≥8% during Screening.
    - In participants in Cohorts A, B, and C1, prescreening ALSFRS-R slope >-
    0.4 points/month, where prescreening ALSFRS-R slope is defined as:
    (ALSFRS-R score at Screening - 48) / (months from date of symptom onset to date of Screening). This criterion is not applicable for Cohorts C2, D1, and D2.
    - Treatment with another investigational drug (including investigational
    drugs for ALS through compassionate use programs) or biological agent
    within 1 month or 5 half-lives of study agent, whichever is longer, before
    Screening.
    -Treatment with an approved disease-modifying therapy for ALS other
    than riluzole or edaravone within 1 month or 5 half-lives of therapy,
    whichever is longer, before screening.
    - Treatment with an antiplatelet or anticoagulant therapy that cannot
    safely be interrupted for lumbar puncture (LP) according to local
    standard of care and/or institutional guidelines, in the opinion of the
    Investigator or Prescriber.
    - Female participants who are pregnant or currently breastfeeding and
    those intending to become pregnant during the study.
    Part 2:
    - History or positive test result at Screening for HIV. If participants from
    Cohorts D1 and D2 who would seamlessly roll from Part 1 into Part 2 test
    positive for HIV during screening for Part 2 but are clinically
    asymptomatic, they may enroll in Part 2 at the discretion of the
    Investigator.
    -Current hepatitis C infection. If participants from Cohorts D1 and D2
    who would seamlessly roll from Part 1 into Part 2 test positive for
    hepatitis C during screening for Part 2 but are clinically asymptomatic,
    they may enroll in Part 2 at the discretion of the Investigator.
    - Current hepatitis B infection. If participants from Cohorts D1 and D2
    who would seamlessly roll from Part 1 into Part 2 test positive for
    hepatitis B during screening for Part 2 but are clinically asymptomatic,
    they may enroll in Part 2 at the discretion of the Investigator.
    - History of alcohol or substance abuse ≤ 6 months of Screening that
    would limit participation in the study, as determined by the Investigator.
    - Current or anticipated need, in the opinion of the Investigator, of a
    diaphragm pacing system during the study period.
    - In participants from Cohorts A, B, C1, and D1, history of myocardial
    infarction, as determined by the Investigator.
    - In participants from Cohorts A, B, C1, and D1, poorly controlled type 1
    or 2 diabetes mellitus defined as HbA1c ≥ 8% during Screening.
    -Treatment with another investigational drug (including investigational
    drugs for ALS through compassionate use programs; excluding BIIB105)
    or biological agent within 1 month or 5 half-lives of study agent,
    whichever is longer, before Screening.
    - Treatment with an antiplatelet or anticoagulant therapy that cannot
    safely be interrupted for LP according to local standard of care and/or
    institutional guidelines, in the opinion of the Investigator or Prescriber.
    - Female participants who are pregnant or currently breastfeeding and
    those intending to become pregnant during the study.
    NOTE: Other protocol defined Exclusion criteria may apply.


    E.5 End points
    E.5.1Primary end point(s)
    Part 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
    Part 2: Number of Participants with AEs and SAEs
    E.5.1.1Timepoint(s) of evaluation of this end point
    Part 1: Up to Day 260
    Part 2: Up to Day 820
    E.5.2Secondary end point(s)
    Part 1:
    1. Serum Concentration of BIIB105
    2. CSF Concentrations of BIIB105
    3. Area Under the Serum Concentration-Time Curve from Time Zero to
    Infinity (AUCinf)
    4. Area Under the Serum Concentration-Time Curve From Time Zero to
    Time of the Last Measurable Concentration (AUClast)
    5. Maximum Observed Serum Concentration (Cmax)
    6. Time to Reach Maximum Observed Serum Concentration (Tmax)
    7. Elimination Half-Life (t1/2) in Serum
    8. Change From Baseline in Plasma Levels of Neurofilament Light Chain
    (NfL)
    Integrated Parts 1 and 2:
    1.CSF Through PK Concentration of BIIB105
    2.Serum PK Concentration of BIIB105
    3.Change From Part 1 Baseline in Plasma Levels of NfL
    4.Change From Part 1 Baseline in Slow Vital Capacity (SVC)
    5.Change From Part 1 Baseline in Amyotrophic Lateral Sclerosis
    Functional Rating Scale – Revised (ALSFRS-R) Score
    6.Change From Part 1 Baseline in Muscle Strength, as Measured by
    Handheld Dynamometry (HHD)
    7.Time to Death or Permanent Ventilation
    8.Time to Death
    9.Time to Death, Incorporating Post-Study Withdrawal or Study
    Completion Vital Status Data
    E.5.2.1Timepoint(s) of evaluation of this end point
    Part 1:
    1.Up to Day 176
    2.Up to Day 259
    3.Up to Day 176
    4.Up to Day 176
    5.Up to Day 176
    6.Up to Day 176
    7.Up to Day 176
    8.Up to Day 259
    Integrated Parts 1 and 2:
    1.Up to Day 819
    2.Up to Day 673
    3.Up to Day 819
    4.Up to Day 819
    5.Up to Day 819
    6.Up to Day 819
    7.Up to Day 820
    8.Up to Day 820
    9.Up to Day 820
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Part 2 is an unblinded long term extension
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial9
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA3
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    United States
    Netherlands
    Spain
    Italy
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 69
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 29
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 12
    F.4.2.2In the whole clinical trial 98
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-06-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-11-18
    P. End of Trial
    P.End of Trial StatusOngoing
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