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The European Union Clinical Trials Register allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   41232   clinical trials with a EudraCT protocol, of which   6757   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
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    Summary
    EudraCT Number:2020-004590-51
    Sponsor's Protocol Code Number:233AS303
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-03-19
    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 ConcernedGermany - BfArM
    A.2EudraCT number2020-004590-51
    A.3Full title of the trial
    A Phase 3 Randomized, Placebo-Controlled Trial With a Longitudinal Natural History Run-In and Open-Label Extension to Evaluate BIIB067 Initiated in Clinically Presymptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of BIIB067 When Initiated in Clinically Presymptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation
    A.3.2Name or abbreviated title of the trial where available
    ATLAS
    A.4.1Sponsor's protocol code number233AS303
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04972487
    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
    B.5.3 Address:
    B.5.3.1Street AddressInnovation House, 70 Norden Road
    B.5.3.2Town/ cityMaidenhead, Berkshire
    B.5.3.3Post codeSL6 4AY
    B.5.3.4CountryUnited Kingdom
    B.5.6E-mailclinicaltrials@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 BIIB067 (ISIS666853)
    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 INNtofersen
    D.3.9.1CAS number 2088232-70-4
    D.3.9.2Current sponsor codeBIIB067 (ISIS 666853)
    D.3.9.3Other descriptive nameBIIB067
    D.3.9.4EV Substance CodeSUB179869
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number6.7
    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 Yes
    D.3.11.13.1Other medicinal product typesecond-generation chimeric 2′ methoxyethyl mixed backbone antisense oligonucleotide (ASO) inhibitor of human SOD1 messenger ribonucleic acid (mRNA).
    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
    Amyotrophic Lateral Sclerosis (ALS)
    E.1.1.1Medical condition in easily understood language
    Lou Gehrig's disease
    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 20.0
    E.1.2Level PT
    E.1.2Classification code 10077024
    E.1.2Term Familial amyotrophic lateral sclerosis
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    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 Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is to evaluate the efficacy of BIIB067 when initiated in presymptomatic adult carriers of a superoxide dismutase 1 (SOD1) mutation with elevated neurofilament (NF).
    E.2.2Secondary objectives of the trial
    The secondary objectives of this study are to evaluate the safety and tolerability of BIIB067 and to evaluate the effect of BIIB067 on pharmacodynamics (PD)/treatment response biomarkers when initiated prior to versus at the time of emergence of clinically manifest amyotrophic lateral sclerosis (ALS).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Key Part A Inclusion Criteria:
    - Participants should have a protocol-defined rapidly progressive SOD1 mutation, confirmed by a central reader, or a SOD1 mutation that is approved for inclusion by an external mutation adjudication committee.
    - Participants with plasma NfL level less than the protocol-defined threshold.
    - Participants who are clinically presymptomatic for ALS (i.e., must not have clinically manifest ALS).
    E.4Principal exclusion criteria
    Key Part A Exclusion Criteria:
    - History or positive test result at screening for human immunodeficiency
    virus (HIV). The requirement for testing at Screening may be omitted if
    it is not permitted by local regulations.
    - Current hepatitis C infection (defined as positive Hepatitis C Virus
    (HCV) antibody and detectable HCV RNA). Participants with positive HCV
    antibody and undetectable HCV Ribonucleic Acid (RNA) are eligible to
    participate in the study (United States Centers for Disease Control and
    Prevention).
    - Current hepatitis B infection (defined as positive for hepatitis B surface
    antigen (HBsAg) and/or anti-Hepatitis B Core antibody (HBc)).
    Participants with immunity to hepatitis B from previous natural infection
    (defined as negative HBsAg, positive anti-HBc, and positive antihepatitis
    B surface antibody (HBs) or vaccination (defined as negative
    HBsAg, negative anti-HBc, and positive anti- HBs) are eligible to
    participate in the study.
    - History of systemic hypersensitivity reaction to tofersen, the excipients
    contained in the formulation, and if appropriate, any diagnostic agents to
    be administered during the study.
    - History of confounding neuromuscular or neurological disorder that is
    expected to have a progressive (i.e., worsening) course during the
    study, and/or is expected to be associated with elevations in NF, in the
    opinion of the Investigator.
    - Presence of risk for increased or uncontrolled bleeding and/or risk of
    bleeding that if not managed optimally could place a participant at an
    increased risk for intraoperative or postoperative bleeding.
    - Significant cognitive impairment, clinical dementia, or unstable
    psychiatric illness, including psychosis, suicidal ideation, suicide
    attempt, or untreated major depression ≤ 90 days of Screening, which in
    the opinion of the Investigator would interfere with the study
    procedures.
    - Treatment with riluzole and/or edaravone. Of the participant has been
    on riluzole and/or edaravone, the medication(s) must be discontinued
    for at least 5 half-lives prior to screening.
    - Use of-label treatments for ALS.
    - Treatment with another investigational drug (including investigational
    drugs for ALS through compassionate use programs), biological agent, or
    device within 1 month or 5 half-lives of study agent, whichever is longer.
    Specifically, no prior treatment with small interfering RNA, stem cell
    therapy, or gene therapy is allowed.
    - Anticipated need, in the opinion of the Investigator, for administration
    of any antiplatelet or anticoagulant medication (e.g., clopidogrel) that
    cannot be safely continued or held for an LP procedure, if necessary,
    according to local or institutional guidelines and/or Investigator
    determination.
    - Current enrollment or a plan to enroll in any interventional clinical
    study in which an investigational treatment, biological agent, device, or
    approved therapy for investigational use. Participation in a
    noninterventional study focused on ALS natural history may be allowed
    at the discretion of the Investigator.

    NOTE: Other protocol defined Inclusion/Exclusion criteria will apply.
    E.5 End points
    E.5.1Primary end point(s)
    Parts B and C: Percentage of Participants with Emergence of Clinically Manifested ALS Within 12 Months of Part B Baseline
    E.5.1.1Timepoint(s) of evaluation of this end point
    Up to 12 months
    E.5.2Secondary end point(s)
    1. Parts B and C: Percentage of Participants with Emergence of Clinically Manifested ALS Within 24 months of Part B Baseline
    2. Parts B and C: Time to Emergence of Clinically Manifest ALS
    3. Parts B and C: Change in ALS Functional Rating Scale (ALSFRS-R) Total Score
    4. Parts B and C: Change from Baseline in Percent Predicted Slow Vital Capacity (SVC)
    5. Parts B and C: Percentage of Participants with Outcome as Death or
    Permanent Ventilation Based on time to Death or Permanent Ventilation
    Analysis
    6. Parts B and C: Percentage of Participants with Outcome as Deaths
    Based on Time to Death Analysis
    7. Parts B, C and D: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) during the Treatment Period
    8. Parts B, C and D: Change from Baseline in Plasma NfL Concentrations
    9. Parts B, C and D: Change in Total Cerebrospinal Fluid (CFL) SOD1 Concentrations
    E.5.2.1Timepoint(s) of evaluation of this end point
    Part B, C and D: Up to 2 years
    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 No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 A: Natural History Run-in: blood draws approx. every 28 days to access NfL levels
    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 trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA10
    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
    Australia
    Belgium
    Brazil
    Canada
    France
    Germany
    Italy
    Japan
    Korea, Republic of
    Poland
    Russian Federation
    Spain
    Sweden
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    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
    The end of study is last protocol-specified contact with the last participant.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months3
    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 months3
    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: 105
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 45
    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 state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 48
    F.4.2.2In the whole clinical trial 150
    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)
    The plan for treatment or care after the subject has ended the participation in the trial is to be defined on case-by-case basis, as the usual treatment will be administered, if required, in accordance with the trial site’s standard of care and generally accepted medical practice, and depending on the subject’s individual medical needs.
    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 Decision2021-07-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-09-15
    P. End of Trial
    P.End of Trial StatusOngoing
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