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    Summary
    EudraCT Number:2021-003417-19
    Sponsor's Protocol Code Number:BN42644
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-10-25
    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 ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2021-003417-19
    A.3Full title of the trial
    A TWO-PART, SEAMLESS, MULTI-CENTER, RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS AND EFFICACY OF RO7204239 IN COMBINATION WITH RISDIPLAM (RO7034067) IN PATIENTS WITH SPINAL MUSCULAR ATROPHY
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of RO7204239 in Combination with Risdiplam (RO7034067) in Patients with Spinal Muscular Atrophy
    A.4.1Sponsor's protocol code numberBN42644
    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 SponsorF.Hoffmann-La Roche Ltd
    B.1.3.4CountrySwitzerland
    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 supportF. Hoffmann-La Roche Ltd
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF. Hoffmann-La Roche Ltd
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.6E-mailglobal.rochegenentechtrials@roche.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.3.1Product nameN/A
    D.3.2Product code RO7204239/F01-01
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNN/A
    D.3.9.1CAS number N/A
    D.3.9.2Current sponsor codeRO7204239
    D.3.9.3Other descriptive nameGYM329
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number80
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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.IMP: 2
    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 Yes
    D.2.1.1.1Trade name Evrysdi
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH, Germany
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/19/2145
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Powder for oral solution
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRisdiplam
    D.3.9.2Current sponsor codeRO7034067
    D.3.9.4EV Substance CodeSUB193759
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    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.IMP: 3
    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.3.1Product nameN/A
    D.3.2Product code RO7204239/F03-01
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNN/A
    D.3.9.1CAS number N/A
    D.3.9.2Current sponsor codeRO7204239
    D.3.9.3Other descriptive nameGYM329
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number90 to 0.75
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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 placeboSubcutaneous use
    D.8 Placebo: 2
    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 placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Spinal Muscular Atrophy (SMA)
    E.1.1.1Medical condition in easily understood language
    SMA is a group of hereditary diseases that destroys nerve cells in the spinal cord that control essential skeletal muscle activity such as speaking, walking, breathing, and swallowing.
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10051203
    E.1.2Term Spinal muscular atrophy congenital
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10041583
    E.1.2Term Spinal muscular atrophy, unspecified
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10079413
    E.1.2Term Spinal muscular atrophy type I
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10079415
    E.1.2Term Spinal muscular atrophy type III
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10079416
    E.1.2Term Spinal muscular atrophy type II
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10079417
    E.1.2Term Spinal muscular atrophy infantile onset
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10079418
    E.1.2Term Spinal muscular atrophy later onset
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10079419
    E.1.2Term Spinal muscular atrophy pre-symptomatic
    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
    Part 1 Ambulant Cohorts A-C
    • Evaluation of the safety of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam
    • Evaluation of pharmacokinetic (PK) parameters for RO7204239 when administered in combination with risdiplam
    • Evaluation of PK parameters for risdiplam when administered in combination with RO7204239
    • Evaluation of the immune response to RO7204239 in combination with risdiplam
    • Evaluation of the pharmacodynamic (PD) effects of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam
    • Evaluation of RO7204239 PK/PD effects
    Part 2
    • Evaluation of the efficacy of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam
    E.2.2Secondary objectives of the trial
    Part 2
    • Evaluation of the efficacy and PD of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam
    • Evaluation of the safety of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam
    • Evaluation of PK parameters for RO7204239 when administered in combination with risdiplam
    • Evaluation of PK parameters for risdiplam when administered in combination with RO7204239
    • Evaluation of immune response to RO7204239 in combination with risdiplam
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Confirmed genetic diagnosis of 5q-autosomal recessive SMA
    • Part 2 only: available survival of motor neuron 2 gene copy number as previously determined by genetic testing and recorded in the participant's medical history
    • Symptomatic SMA disease, as per investigator’s clinical judgement
    • Age at screening:
    o Part 1 Cohorts A, B, and D: 5-10 years, inclusive
    o Part 1 Cohort C: 2-4 years, inclusive
    o Part 2: 2-25 years, inclusive
    • For Part 1 Cohorts A, B, and C and Part 2 only: Participants who are ambulant, where ambulant is defined as able to walk/run unassisted (i.e., without the use of assistive devices such as canes, walking sticks, crutches, walkers, person/hand held assistance, braces, orthoses, over the malleoli insoles or any other type of support) 10 meters in <= 30 seconds as measured by the Timed 10-Meter Walk/Run Test [10MWRT]) at screening
    • For Part 1 Cohort D only: Participants who are able to sit, defined by:
    o A score of 3 on Item 9 of the Motor Function Measure-32 item (MFM32)
    o A score of at least 2 on Item 10 of the MFM32
    • For Part 1 Cohort D only: Participants who are able to raise a standardized plastic cup with a 200 g weight in it to the mouth, using both hands if necessary, defined by a score of 3 on the entry item of the Revised Upper Limb Module (RULM)
    • Participants who have received previous SMA disease-modifying therapies may be included provided that
    o Onasemnogene abeparvovec was received at least 90 days prior to screening. Participants should be tapered off steroids prior to receiving risdiplam. In addition, participants should have normal levels of liver function tests, coagulation parameters, platelets, and troponin-I at 90 days after administration of onasemnogene abeparvovec or at least 1 month after tapering off corticosteroids, whichever comes later
    o Nusinersen last dose was received at least 90 days prior to screening
    o Risdiplam is switched to the investigational medicinal product (IMP) provided by the site
    • Able and willing to comply with the study protocol and to complete all study procedures, measurements, and visits
    • Negative pregnancy test at screening for females of childbearing potential
    • Females of childbearing potential or who may reach childbearing potential during the study: must agree to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for both 17 months after the final dose of RO7204239 and 28 days after the final dose of risdiplam
    • For males who are expected to reach sexual maturity during the study: participants must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agree to refrain from donating sperm during the treatment period and for 28 days after the final dose of risdiplam and 4 months after the final dose of RO7204239
    E.4Principal exclusion criteria
    • For Part 1 Cohorts A and B only: Participants with contraindications for magnetic resonance imaging (MRI) scan, difficulties maintaining a prolonged supine position, or any other clinical history or examination finding that would pose a potential hazard in combination with MRI
    • Part 1 Cohort D only:
    o Participants who are unable to adopt the correct position to ensure adequate quality of dual-energy X-ray absorptiometry (DXA) scan acquisition, as determined by the DXA scan technologist
    o Participants who have contractures at screening that would interfere with DXA scan acquisition or functional assessments, as confirmed by the DXA scan technologist and clinical evaluator
    o For participants able to take steps only: Able to walk unassisted 10 meters in <= 30 seconds as measured by the timed 10MWRT at screening
    o Participants who have severe scoliosis (curvature > 40°) at screening based on the participant's most recent X ray as performed per standard of care or scoliosis that would interfere with functional assessments, as confirmed by the clinical evaluator. An X-ray is not required if it is not clinically indicated
    o Participants who require invasive ventilation, tracheostomy, or the use of non-invasive ventilation during the daytime
    • For Part 2 only: Participants who recently initiated treatment (within 6 months prior to screening) with oral salbutamol or another β2-adrenergic agonist taken orally
    • Concomitant or previous participation in any investigational drug or device study within 90 days prior to screening, or 5 half-lives of the drug, whichever is longer. For those who have completed a risdiplam study, or participated in a nusinersen or onasemnogene abeparvovec study, the same as described under inclusion criteria apply
    • Received previous administration of anti-myostatin therapies
    • Any history of cell therapy
    • Hospitalized for a pulmonary event within the last 2 months or planned hospitalization at the time of screening
    • Previous surgery for scoliosis or hip fixation in the 6 months preceding screening or planned within the next 9 months (Part 1) or 21 months (Part 2)
    • Unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular system diseases considered to be clinically significant
    • Clinically significant electrocardiography (ECG) abnormalities at screening
    • Clinically significant abnormal findings at echocardiography at screening from average of triplicate measurement or cardiovascular disease indicating a safety risk for participants
    • Any major illness within 1 month before screening
    • Received any multidrug and toxin extrusion1/2K (MATE) substrates within 2 weeks before screening
    • Hereditary fructose intolerance
    • Use of any of the following medications within 90 days prior to screening: riluzole, valproic acid, hydroxyurea, sodium phenylbutyrate, butyrate derivatives, creatine, carnitine, growth hormone, anabolic steroids, probenecid, acetyl cholinesterase inhibitors, agents that could potentially increase or decrease muscle strength, and agents with known or presumed histone deacetylase (HDAC) inhibitory effect
    • Clinically significant abnormalities in laboratory test results
    • Ascertained or presumptive hypersensitivity to RO7204239 or risdiplam, or to the constituents of their formulations
    • Concomitant disease or a condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would pose an unacceptable risk to the participant in this study
    • History of any malignancy
    • Any clinically relevant history of anaphylactic reaction requiring inotropic support
    • Any abnormal skin conditions, pigmentation or lesions in the area intended for subcutaneous (SC) injection (abdomen) and that would prevent visualization of potential injection site reactions to RO7204239
    • Immobilization, surgical procedures, fracture, or trauma to the upper or lower limbs within 90 days prior to screening
    • Female participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within either 17 months after the final dose of RO7204239 or 28 days after the final dose of risdiplam
    E.5 End points
    E.5.1Primary end point(s)
    Part 1 Ambulant Cohorts A-C
    1. Incidence, severity, and causal relationship of adverse events (AEs), with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0)
    2. Change from baseline in vital signs, physical findings, ECG, echocardiogram, relevant echocardiographic parameters and clinical laboratory results
    3. Incidence of local and systemic injection reactions
    4. Incidence of abnormal laboratory findings
    5. Incidence of abnormal ECG parameters
    6. Incidence of relevant echocardiographic parameter z scores >2
    7. Incidence of abnormal vital signs
    8. Serum concentration of RO7204239 at specified timepoints
    9. Maximum observed concentration (Cmax) of RO7204239 at specified timepoints
    10. Area under the concentration-time curve (AUC) of RO7204239 at specified timepoints
    11. Trough concentration (Ctrough) of RO7204239 at specified timepoints
    12. Plasma concentration of risdiplam (and its metabolite M1) at specified timepoints
    13. Cmax of risdiplam (and its metabolite M1) at specified timepoints
    14. AUC of risdiplam (and its metabolite M1) at specified timepoints
    15. Ctrough of risdiplam (and its metabolite M1) at specified timepoints
    16. Prevalence of anti-drug antibodies (ADAs) against RO7204239 at baseline and incidence of ADAs during the study
    17. Change from baseline in serum concentrations of total and free latent myostatin, and mature myostatin
    18. Percentage change from baseline in the contractile area of skeletal muscle in the dominant thigh as assessed by MRI (participants >=5 years) at Week 24 of combination treatment
    19. Percentage change from baseline in the contractile area of skeletal muscle in the dominant calf as assessed by MRI (participants >=5 years) at Week 24 of combination treatment
    20. Relationship between PK/PD endpoints, ADA status, and safety or efficacy
    Part 2
    21. Change from baseline in the Revised Hammersmith Scale (RHS) total score at Week 72 of combination treatment (Study Week 80)
    E.5.1.1Timepoint(s) of evaluation of this end point
    1-11. Throughout the study at specified timepoints
    12-15. At Week 21
    16. Throughout the study at specified timepoints
    17. Up to Week 85
    18-19. At Week 24
    20. Up to Week 96
    21. At Week 72
    E.5.2Secondary end point(s)
    Part 2
    1. Change from baseline in MFM Domain 1 + Domain 2 (D1 + D2) score at Week 72 of combination treatment (Study Week 80)
    2. Change from baseline in MFM-32 item total score at Week 72 of combination treatment (Study Week 80)
    3. Change from baseline in the time taken to rise from floor as measured by RHS Item 25 at Week 72 of combination treatment (Study Week 80)
    4. Change from baseline in the time taken to walk/run 10 meters as measured by RHS Item 19 at Week 72 of combination treatment (Study Week 80)
    5. Percent change from baseline in lean mass as assessed by full-body DXA scan (participants >=5 years) at Week 72 of combination treatment (Study Week 80)
    6. Incidence, severity, and causal relationship of AEs, with severity determined according to NCI CTCAE v5.0
    7. Change from baseline in vital signs, physical findings, ECG, echocardiogram, relevant echocardiographic parameters and clinical laboratory results
    8. Incidence of local and systemic injection reactions
    9. Incidence of abnormal laboratory findings
    10. Incidence of abnormal ECG parameters
    11. Incidence of relevant echocardiographic parameter z scores >2
    12. Incidence of abnormal vital signs
    13. Serum concentration of RO7204239 at specified timepoints
    14. Cmax of RO7204239 at specified timepoints
    15. AUC of RO7204239 at specified timepoints
    16. Ctrough of RO7204239 at specified timepoints
    17. Plasma concentration of risdiplam (and its metabolite M1) at specified timepoints
    18. Cmax of risdiplam (and its metabolite M1) at specified timepoints
    19. AUC of risdiplam (and its metabolite M1) at specified timepoints
    20. Ctrough of risdiplam (and its metabolite M1) at specified timepoints
    21. Prevalence of ADAs at baseline and incidence of ADAs during the study; Impact of ADA on PK, PD, safety and efficacy parameters
    E.5.2.1Timepoint(s) of evaluation of this end point
    1-5. At week 72
    6-16. Throughout the study at specified timepoints
    17-20. At week 24
    21. Throughout the study at specified timepoints
    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 Yes
    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 No
    E.6.11Pharmacogenomic No
    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) Yes
    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 No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Placebo + Risdiplam
    E.8.2.4Number of treatment arms in the trial8
    E.8.3 The trial involves single site in the Member State concerned Information not present in EudraCT
    E.8.4 The trial involves multiple sites in the Member State concerned Information not present in EudraCT
    E.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA23
    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
    United Kingdom
    United States
    Belgium
    Germany
    Italy
    Netherlands
    Poland
    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 this study is defined as the date of the last visit of the last participant in the study or the date at which the last data point required for statistical analysis (i.e., for the final analysis) or safety follow-up is received from the last participant in the study, whichever occurs later.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days21
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months9
    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 Yes
    F.1.1Number of subjects for this age range: 180
    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) Yes
    F.1.1.5.1Number of subjects for this age range: 180
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Informed consent for study participation will be obtained from parents or legal guardian
    F.3.3.7Others Yes
    F.3.3.7.1Details of other specific vulnerable populations
    Pediatric population
    F.4 Planned number of subjects to be included
    F.4.1In the member state13
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 90
    F.4.2.2In the whole clinical trial 180
    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 Sponsor will offer continued access to Roche IMP RO7204239 or Risdiplam free of charge to eligible participants in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product. For detailed information refer to protocol BN42644, section 6.7 Continued access to study treatment after the end of the study.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Signant Health
    G.4.3.4Network Country United States
    G.4 Investigator Network to be involved in the Trial: 2
    G.4.1Name of Organisation IQVIA
    G.4.3.4Network Country United Kingdom
    G.4 Investigator Network to be involved in the Trial: 3
    G.4.1Name of Organisation W&G Linney Limited
    G.4.3.4Network Country United Kingdom
    G.4 Investigator Network to be involved in the Trial: 4
    G.4.1Name of Organisation Greenphire, Inc.
    G.4.3.4Network Country United States
    G.4 Investigator Network to be involved in the Trial: 5
    G.4.1Name of Organisation Marken LLC
    G.4.3.4Network Country United States
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-01-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-11-04
    P. End of Trial
    P.End of Trial StatusOngoing
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