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A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Risdiplam (RO7034067) in Type 2 and 3 Spinal Muscular Atrophy (SMA) Participants (SUNFISH)

Primary Purpose

Muscular Atrophy, Spinal

Status

Active

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Placebo

Risdiplam

About this trial

This is an interventional treatment trial for Muscular Atrophy, Spinal

Eligibility Criteria

2 Years - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Confirmed diagnosis of 5q-autosomal recessive SMA
Negative blood pregnancy test at screening and agreement to comply with measures to prevent pregnancy and restrictions on sperm donation
For Part 1: Type 2 or 3 SMA ambulant or non-ambulant
For Part 2: 1) Type 2 or 3 SMA non-ambulant; 2) RULM entry item A greater than or equal to 2; 3) ability to sit independently as assessed by item 9 of the MFM

Exclusion Criteria:

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
Concomitant or previous administration of a SMN2-targeting antisense oligonucleotide, SMN2 splicing modifier or gene therapy either in a clinical study or as part of medical care
Any history of cell therapy
Hospitalization for a pulmonary event within the last 2 months or planned at time of screening
Surgery for scoliosis or hip fixation in the one year preceding screening or planned within the next 18 months
Unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular system diseases as considered to be clinically significant by the Investigator
Presence of clinically significant electrocardiogram abnormalities before study drug administration from average of triplicate measurement or cardiovascular disease indicating a safety risk for participants as determined by the Investigator
Any major illness within one month before the screening examination or any febrile illness within one week prior to screening and up to first dose administration
Recently initiated treatment (within less than [<] 6 months prior to randomization) with oral salbutamol or another beta 2-adrenergic agonist taken orally
Any prior use of chloroquine, hydroxychloroquine, retigabin, vigabatrin or thioridazine, is not allowed
Ascertained or presumptive hypersensitivity (e.g., anaphylactic reaction) to Risdiplam or to the constituents of its formulation
Recent history (less than one year) of ophthalmological diseases
Participants requiring invasive ventilation or tracheostomy

Sites / Locations

Stanford University Medical Center
Columbia University Medical Center; The Neurological Institute of New York
UZ Gent
UZ Leuven Gasthuisberg
Chr de La Citadelle
Instituto de Puericultura E Pediatria Martagão Gesteira
Alberta Children's Hospital Division of Pediatric Neurology
London Health Sciences Centre; Children's Hospital; Pediatrics
McGill University Health Centre - Glen Site
Peking University First Hospital
Children's Hospital of Fudan University
Clinical Medical Center Zagreb; University Hospital Rebro Department of Paediatrics
Hopital Femme Mere Enfant; Medecine Physique et Readaptation Pediatrique ? L?ESCALE
Hopital Roger Salengro
CHU de Nantes - Hotel Dieu
Hôpital Necker-Enfants Malades; Service de neuropédiatrie
Hopital Armand Trousseau
Universitätsklinikum Freiburg; Klinik für Neuropädiatrie und Muskelerkrankungen
IRCCS Ospedale Pediatrico Bambino Gesù; U.O. Malattie Neuromuscolari e Neurodegenerative
Policlinico Agostino Gemelli; Dipartimento di Neuropsichiatria Infantile
IRCCS Istituto Giannina Gaslini; U.O.S.D. Centro di Miologia e Patologie Neurodegenerative
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Unità Operativa Complessa di Neurologia
Fondazione IRCCS Istituto Neurologico ?Carlo Besta?; UO di Neurologia dello Sviluppo
Fukuoka Children's Hospital
Hiroshima University Hospital
Hyogo Medical University Hospital
Minami Kyushu National Hospital
Miyagi Children's Hospital
Shiga Medical Center for Children
Shizuoka Children's Hospital
Jichi Medical University Hospital
Center Hospital of the National Center for Global Health and Medicine
National Center Of Neurology And Psychiatry Hospital
Szpital Gdanskiego Uniwersytetu Medycznego; Clinic of developmental neurology
Uniwersytecki Szpital Kliniczny w Poznaniu; Od. Kliniczny Neurologii Dzieci i M?odziezy
Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie
Russian Children Neuromuscular Center of Veltischev
Clinic for Neurology and Psychiatry for Children and Youth
Hospital Sant Joan De Deu
Hospital Universitari Vall d'Hebron; Servicio de Reumatologia
Hospital Universitario La Paz
Hospital Universitario Virgen del Rocío
Hacettepe University, School of Medicine; Pediatrics Department; Pediatrics Child Neurology Unit
Hospital Yeditepe University Kozyatagi; Pediatry
University of Oxford; Department of Paediatrics

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Arm Label

Part 1 Group A: Adolescents and Adults (Risdiplam)

Part 1 Group A: Adolescents and Adults (Placebo)

Part 1 Group B: Children (Placebo)

Part 1 Group B: Children (Risdiplam)

Part 2: Placebo

Part 2: Risdiplam

Arm Description

Adolescent and adult participants aged 12-25 years will receive risdiplam for at least 12 weeks. Once the placebo-controlled period is completed and Part 2 dose is selected, participants will be switched to Part 2 dose and will be treated in an open-label phase.

Adolescent and adult participants aged 12-25 years will receive placebo matching to risdiplam for at least 12 weeks. Once placebo-controlled period is completed, participants will be first switched to their cohort risdiplam dose. After the Part 2 dose is selected, participants will be switched to Part 2 dose and will be treated in an open-label phase.

Children aged 2-11 years will receive placebo matching to risdiplam for at least 12 weeks. Once placebo-controlled period is completed, participants will be first switched to their cohort risdiplam dose. After the Part 2 dose is selected, participants will be switched to Part 2 dose and will be treated in an open-label phase.

Children aged 2-11 years will receive risdiplam for at least 12 weeks. Once the placebo-controlled period is completed and Part 2 dose is selected, participants will be switched to Part 2 dose and will be treated in an open-label phase.

Participants aged 2-25 years will receive placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants will be switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment until Month 24. After Month 24, participants will be offered the opportunity to enter the open-label phase.

Participants aged 2-25 years will receive risdiplam at the dose selected based on the results from Part 1 of the study (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg), for 24 months. After 24-month treatment, participants will be offered the opportunity to enter the open-label phase.

Outcomes

Primary Outcome Measures

Part 1: Selected Part 2 Dose of Risdiplam for Participants With a Body Weight (BW) of >/=20kg

The Internal Monitoring Committee (IMC) was responsible for selecting the dose for Part 2 of the study (pivotal dose). An external Independent Data Monitoring Committee (iDMC) reviewed data from Part 1 and confirmed the dose-selection decision of the IMC. The dose for Part 2 selected by the IMC was a dose that: 1.Was judged to be safe and well-tolerated, based on all available safety data from Part 1 and as confirmed by the iDMC; 2. Resulted in an exposure at steady-state below the exposure cap (mean value) of AUC0-24h,ss 2000 ng*h/mL (adjusted for free-fraction, if required); 3. Resulted in an SMN protein increase that was expected to be clinically relevant.

Part 1: Selected Part 2 Dose of Risdiplam for Participants With BW of <20kg

Part 2: Change From Baseline in the Total Motor Function Measure 32 (MFM-32) Total Score at Month 12

The Motor Function Measure 32 (MFM32) is a scale constructed for use in neuromuscular disorders. It comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The 32 scores are summed and expressed on a 0-100 scale for the MFM32 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on primary efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Secondary Outcome Measures

Part 2: Percentage of Participants With Marked Improvement (Defined as >= 3) in the Total Motor Function Measure (MFM32) Score at Month 12

The MFM32 comprises 32 items that evaluate physical function. The scoring of each task uses a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The 32 scores are summed and expressed on a 0-100 scale for the MFM32 total score. A change in MFM32 total score of threshold >/=3 represents marked improvement in this measure. Logistic regression analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Change From Baseline in the Total Score of the Revised Upper Limb Module (RULM) at Month 12

The RULM is a 20 items scale that assesses the proximal and distal motor functions of the arm. There is an entry item and the remaining 18 items are scored on the 3 point scale of: 0: cannot complete task independently; 1: modified method but can complete task independently; 2: completes task without any assistance, and with 1 item scored on a 2 point scale of as a can/cannot score with 1 as the highest score. The RULM total score is the sum of 19 items scores with range of 0-37, and the entry item does not contribute to the total score. Higher scores indicate greater upper limb function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on the efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Change From Baseline in Total Score of Hammersmith Functional Motor Scale Expanded (HFMSE) at Month 12

The HFMSE scale contains 33 items, which are scored on a 3-point Likert-type scale (0-2) and summed to derive the total score, with lower scores indicating greater impairment. The HFMSE contains a series of assessments designed to assess important functional abilities, including standing, transfers, ambulation, and proximal and axial function. The overall score is the sum of the scores for all activities with a maximum achievable score of 66. Higher scores indicate greater motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on the efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Change From Baseline in Forced Vital Capacity (FVC) at Month 12 in Participants Aged 6-25 Years

Spirometry is a pulmonary function test that assesses how the lungs work by measuring how much air moves through the airways. Spirometry was performed by all participants aged 6 or older. Forced vital capacity (FVC) is the total volume that can be exhaled after inhaling maximally. The best % predicted value out of all attempts were used for the analysis. MMRM analysis was performed based on the efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Change From Baseline in the Caregiver-Reported SMA Independence Scale (SMAIS) Total Score at Month 12

The SMA Independence Scale (SMAIS) was developed specifically for SMA participants in order to assess function-related independence. The SMAIS contains 29 items, assessing the amount of assistance required from another individual to perform daily activities such as eating, or bathing. Each item is scored on a 0-4 scale (with an additional option to indicate that an item is non-applicable). The SMAIS total score ranging from 0-44 is obtained based on 22 items with each item on the 0-2 scale. Lower scores indicate greater dependence on another individual. The SMAIS was completed by participants aged 12 years or older and caregivers of participants aged 2-25 years. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Percentage of Participants Rated by Clinicians as Improved in the Clinical Global Impression of Change (CGI-C) Scale Ratings at Month 12

The Clinical Global Impression of Change (CGI-C) is used to score a clinician's impression of a participant's change in global health. The CGI-C is a single item measure of change in global health, using seven response options: "very much improved", "much improved", "minimally improved", "no change", "minimally worse", "much worse", and "very much worse". Participants considered as "improved" included responses of "very much improved, "much improved" and "minimally improved". Logistic regression analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Percentage of Participants Who Achieve Stabilization or Improvement (Defined as >= 0) in the Total Motor Function Measure (MFM-32) Score at Month 12

The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The 32 scores are summed and expressed on a 0-100 scale for the MFM32 total score. Higher scores indicate increased motor function. Logistic regression analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Percentage of Participants Who Achieve an Improvement of at Least One Standard Error of Measurement on the Total MFM-32 Score at Month 12

The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0-cannot initiate the task or maintain the starting position; 1-performs the task partially; 2-performs the task incompletely or imperfectly; 3-performs the task fully and "normally". The 32 scores are summed and expressed on a 0-100 scale for the total score. Higher scores indicate increased motor function. Standard error of measurement (SEM) is derived using 32 items scores and total scores at baseline. Change from baseline > = one SEM is equivalent to a change >= 4. Logistic regression analysis was performed based on efficacy hypothetical estimand included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Change From Baseline in the MFM-32 Domain 1 (D1) Score at Month 12

The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The D1 items score are summed and expressed on 0-100 scale for the MFM D1 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Change From Baseline in the MFM-32 Domain 2 (D2) Score at Month 12

The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The D2 items score are summed and expressed on 0-100 scale for the MFM D2 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Change From Baseline in the MFM-32 Domain 3 (D3) Score at Month 12

The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The D3 items score are summed and expressed on 0-100 scale for the MFM D3 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Change From Baseline in the Total Combined Scores of MFM-32 Domains 1 and 2 at Month 12

The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The D1+D2 items score are summed and expressed on 0-100 scale for the MFM D1+D2 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Change From Baseline in the Total Combined Scores of MFM-32 Domains 2 and 3 at Month 12

The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The D2+D3 items score are summed and expressed on 0-100 scale for the MFM D2+D3 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Month 12 in Participants Aged 6-25 Years

Spirometry is a pulmonary function test that assesses how the lungs work by measuring how much air moves through the airways. Spirometry was performed by all participants aged 6 or older. Forced expiratory volume (FEV1) is the volume forcefully exhaled in the first second of the forced vital capacity test. The best % predicted value out of all attempts were used for the analysis. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Change From Baseline in the Peak Cough Flow (PCF) at Month 12 in Participants Aged 6-25 Years

Spirometry is a pulmonary function test that assesses how the lungs work by measuring how much air moves through the airways. Spirometry was performed by all participants aged 6 or older. Peak cough flow (PCF) is an assessment of cough strength. The best % predicted value out of all attempts were used for the analysis MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Change From Baseline in the Best Sniff Nasal Inspiratory Pressure (SNIP) at Month 12

The Sniff Nasal Inspiratory Pressure (SNIP) is a volitional, non-invasive test of inspiratory muscle strength that has been successfully applied to children > 2 years of age. Advantages include the simplicity of the maneuver and the absence of a mouthpiece, which is particularly helpful for participants with SMA, who may have bulbar weakness. SNIP also has the advantage of measuring inspiratory pressure during a natural maneuver that is easily performed even by young children with neuromuscular disorders. The best % predicted value out of all attempts were used for the analysis. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Change From Baseline in Maximal Inspiratory Pressure (MIP) at Month 12 in Participants Aged 6-25 Years

The maximal inspiratory pressure (MIP) is a non-invasive test of muscle strength, which measures the maximum strength of the diaphragm and other inspiratory muscles. MIP was measured in participants aged 6 or older. Participants were asked to perform a forceful inspiration against an occluded mouth piece. The best % predicted value out of all attempts were used for the analysis. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Change From Baseline in Maximal Expiratory Pressure (MEP) at Month 12 in Participants Aged 6-25 Years

The maximal expiratory pressure (MEP) is a non-invasive test of muscle strength, which measures the maximum strength of the abdominal muscles and other expiratory muscles. MEP was measured in participants aged 6 or older. Participants were asked to perform a forceful inspiration against an occluded mouth piece. The best % predicted value out of all attempts were used for the analysis. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Change From Baseline in the Participant-Reported SMA Independence Scale (SMAIS) Total Score at Month 12

The SMAIS was developed specifically for SMA participants in order to assess function-related independence. It contains 29 items, assessing the amount of assistance required from another individual to perform daily activities such as eating, or bathing. Each item is scored on a 0-4 scale (with an additional option to indicate that an item is non-applicable). The SMAIS total score ranging from 0-44 is obtained based on 22 items with each item on the 0-2 scale. Lower scores indicate greater dependence on another individual. The SMAIS was completed by participants aged 12 years or older and caregivers of participants aged 2-25 years. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Percentage of Participants Rated by Clinicians as No Change or Improved in the Clinical Global Impression of Change (CGI-C) Scale Ratings at Month 12

The CGI-C is used to score a clinician's impression of a participant's change in global health. It is a single item measure of change in global health, using seven response options: "very much improved", "much improved", "minimally improved", "no change", "minimally worse", "much worse", and "very much worse". Participants considered as "no change or improved" included responses of "no change", "very much improved", "much improved" and "minimally improved". Logistic regression analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Part 2: Percentage of Participants Who Experience at Least One Disease-Related Adverse Event at Month 12

Disease-related adverse events (AEs) were identified by applying two different types of baskets to the AE dataset: Narrow prospectively defined baskets of MedDRA lowest level terms. This basket was defined based on a group of CDC terms selected from an age and gender matched case control study comparing CDC code rates observed in participants with and without SMA using commercially available insurance claim data (CLAIMS and Market scan data). The lowest level terms included in each basket, coded using the latest version of MedDRA; Broad prospectively defined basket with events selected at preferred term level from all AEs reported in ongoing clinical trials up to January 2019, i.e., prior to unblinding of Part 2 of Study BP39055.

Part 2: Number of Disease-related Adverse Events Per Patient-years at Month 12

Disease-related AEs were collected through the AE reporting of the study, and the disease-related AE rate was adjusted for patient years (AE rate per 100 patient-years). They were identified by applying two different types of baskets to the AE dataset: Narrow prospectively defined baskets of MedDRA lowest level terms and Broad prospectively defined basket with events selected at preferred term level from all AEs reported in ongoing clinical trials up to January 2019, i.e., prior to unblinding of Part 2 of Study BP39055.

Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An adverse event (AE) is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Part 2: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) in the Placebo-Controlled Period

Part 2: Percentage of Participants With Treatment Discontinuation Due to Adverse Events (AEs) and Serious Adverse Events (SAEs) in the Placebo-Controlled Period

Part 2: Number of Participants Aged 6-25 Years With Suicidal Ideation Based on Columbia-Suicide Severity Rating Scale (C-SSRS) in the Placebo-Controlled Period

The Columbia Suicide Severity Rating Scale (C-SSRS) is used to assess the lifetime suicidality of a participant (C-SSRS baseline) as well as any new instances of suicidality (C-SSRS since last visit). The structured interview prompts recollection of suicidal ideation, including the intensity of the ideation, behavior, and attempts with actual/potential lethality. The C-SSRS assessments results were collected for participants aged 6 years and older.

Part 2: Number of Participants Aged 6-25 Years With Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) in the Placebo-Controlled Period

Survival of Motor Neuron 2 (SMN2) Messenger Ribonucleic Acid (mRNA) Levels in Blood

Survival of Motor Neuron (SMN) Protein Levels in Blood

Part 1 and 2: Maximum Plasma Concentration (Cmax) of Risdiplam

Part 1 and 2: Area Under the Curve (AUC) of Risdiplam

Part 1 and 2: Concentration at the End of a Dosing Interval (Ctrough) of Risdiplam

Full Information

NCT ID

NCT02908685

First Posted

September 19, 2016

Last Updated

September 8, 2023

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT02908685

Brief Title

A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Risdiplam (RO7034067) in Type 2 and 3 Spinal Muscular Atrophy (SMA) Participants

Acronym

SUNFISH

Official Title

A Two Part Seamless, Multi-Center Randomized, Placebo-Controlled, Double-Blind Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Risdiplam (RO7034067) in Type 2 and 3 Spinal Muscular Atrophy Patients

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

October 20, 2016 (Actual)

Primary Completion Date

September 6, 2019 (Actual)

Study Completion Date

September 29, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary

Multi-center, randomized, double-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of Risdiplam in adult and pediatric participants with Type 2 and Type 3 SMA. The study consists of two parts, an exploratory dose finding part (Part 1) of Risdiplam for 12 weeks and a confirmatory part (Part 2) of Risdiplam for 24 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Muscular Atrophy, Spinal

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Sequential Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

231 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1 Group A: Adolescents and Adults (Risdiplam)

Arm Type

Experimental

Arm Description

Arm Title

Part 1 Group A: Adolescents and Adults (Placebo)

Arm Type

Placebo Comparator

Arm Description

Arm Title

Part 1 Group B: Children (Placebo)

Arm Type

Placebo Comparator

Arm Description

Arm Title

Part 1 Group B: Children (Risdiplam)

Arm Type

Experimental

Arm Description

Arm Title

Part 2: Placebo

Arm Type

Placebo Comparator

Arm Description

Arm Title

Part 2: Risdiplam

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo will be administered orally (via mouth) or through a feeding tube (naso-gastric or gastrostomy tube).

Intervention Type

Drug

Intervention Name(s)

Risdiplam

Other Intervention Name(s)

RO7034067

Intervention Description

Risdiplam will be administered orally (via mouth) or through a feeding tube (naso-gastric or gastrostomy tube).

Primary Outcome Measure Information:

Title

Part 1: Selected Part 2 Dose of Risdiplam for Participants With a Body Weight (BW) of >/=20kg

Description

Time Frame

Day 1 up to at least 4 weeks on study (Up to CCOD of 25 July 2017)

Title

Part 1: Selected Part 2 Dose of Risdiplam for Participants With BW of <20kg

Description

Time Frame

Day 1 up to at least 4 weeks on study (Up to CCOD of 25 July 2017)

Title

Part 2: Change From Baseline in the Total Motor Function Measure 32 (MFM-32) Total Score at Month 12

Description

Time Frame

Baseline (Day-1) and Month 12

Secondary Outcome Measure Information:

Title

Part 2: Percentage of Participants With Marked Improvement (Defined as >= 3) in the Total Motor Function Measure (MFM32) Score at Month 12

Description

Time Frame

At Month 12

Title

Part 2: Change From Baseline in the Total Score of the Revised Upper Limb Module (RULM) at Month 12

Description

Time Frame

Baseline (Day-1) and Month 12

Title

Part 2: Change From Baseline in Total Score of Hammersmith Functional Motor Scale Expanded (HFMSE) at Month 12

Description

Time Frame

Baseline (Day-1) and Month 12

Title

Part 2: Change From Baseline in Forced Vital Capacity (FVC) at Month 12 in Participants Aged 6-25 Years

Description

Time Frame

Baseline (Day-1) and Month 12

Title

Part 2: Change From Baseline in the Caregiver-Reported SMA Independence Scale (SMAIS) Total Score at Month 12

Description

Time Frame

Baseline (Day-1) and Month 12

Title

Part 2: Percentage of Participants Rated by Clinicians as Improved in the Clinical Global Impression of Change (CGI-C) Scale Ratings at Month 12

Description

Time Frame

At Month 12

Title

Part 2: Percentage of Participants Who Achieve Stabilization or Improvement (Defined as >= 0) in the Total Motor Function Measure (MFM-32) Score at Month 12

Description

Time Frame

At Month 12

Title

Part 2: Percentage of Participants Who Achieve an Improvement of at Least One Standard Error of Measurement on the Total MFM-32 Score at Month 12

Description

Time Frame

At Month 12

Title

Part 2: Change From Baseline in the MFM-32 Domain 1 (D1) Score at Month 12

Description

The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The D1 items score are summed and expressed on 0-100 scale for the MFM D1 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Time Frame

Baseline (Day-1) and Month 12

Title

Part 2: Change From Baseline in the MFM-32 Domain 2 (D2) Score at Month 12

Description

The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The D2 items score are summed and expressed on 0-100 scale for the MFM D2 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Time Frame

Baseline (Day-1) and Month 12

Title

Part 2: Change From Baseline in the MFM-32 Domain 3 (D3) Score at Month 12

Description

The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The D3 items score are summed and expressed on 0-100 scale for the MFM D3 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Time Frame

Baseline (Day-1) and Month 12

Title

Part 2: Change From Baseline in the Total Combined Scores of MFM-32 Domains 1 and 2 at Month 12

Description

The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The D1+D2 items score are summed and expressed on 0-100 scale for the MFM D1+D2 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Time Frame

Baseline (Day-1) and Month 12

Title

Part 2: Change From Baseline in the Total Combined Scores of MFM-32 Domains 2 and 3 at Month 12

Description

The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The D2+D3 items score are summed and expressed on 0-100 scale for the MFM D2+D3 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Time Frame

Baseline (Day-1) and Month 12

Title

Part 2: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Month 12 in Participants Aged 6-25 Years

Description

Spirometry is a pulmonary function test that assesses how the lungs work by measuring how much air moves through the airways. Spirometry was performed by all participants aged 6 or older. Forced expiratory volume (FEV1) is the volume forcefully exhaled in the first second of the forced vital capacity test. The best % predicted value out of all attempts were used for the analysis. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Time Frame

Baseline (Day-1) and Month 12

Title

Part 2: Change From Baseline in the Peak Cough Flow (PCF) at Month 12 in Participants Aged 6-25 Years

Description

Spirometry is a pulmonary function test that assesses how the lungs work by measuring how much air moves through the airways. Spirometry was performed by all participants aged 6 or older. Peak cough flow (PCF) is an assessment of cough strength. The best % predicted value out of all attempts were used for the analysis MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.

Time Frame

Baseline (Day-1) and Month 12

Title

Part 2: Change From Baseline in the Best Sniff Nasal Inspiratory Pressure (SNIP) at Month 12

Description

Time Frame

Baseline (Day-1) and Month 12

Title

Part 2: Change From Baseline in Maximal Inspiratory Pressure (MIP) at Month 12 in Participants Aged 6-25 Years

Description

Time Frame

Baseline (Day-1) and Month 12

Title

Part 2: Change From Baseline in Maximal Expiratory Pressure (MEP) at Month 12 in Participants Aged 6-25 Years

Description

Time Frame

Baseline (Day-1) and Month 12

Title

Part 2: Change From Baseline in the Participant-Reported SMA Independence Scale (SMAIS) Total Score at Month 12

Description

Time Frame

Baseline (Day-1) and Month 12

Title

Part 2: Percentage of Participants Rated by Clinicians as No Change or Improved in the Clinical Global Impression of Change (CGI-C) Scale Ratings at Month 12

Description

Time Frame

At Month 12

Title

Part 2: Percentage of Participants Who Experience at Least One Disease-Related Adverse Event at Month 12

Description

Time Frame

Baseline up to Month 12 (Week 52; up to CCOD of 06 September 2019)

Title

Part 2: Number of Disease-related Adverse Events Per Patient-years at Month 12

Description

Time Frame

Baseline up to Month 12 (Week 52; up to CCOD of 06 September 2019)

Title

Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Description

Time Frame

Day 1 on risdiplam up to end of study (up to approximately 7 years)

Title

Part 2: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) in the Placebo-Controlled Period

Description

Time Frame

Day 1 up to 12 months of the placebo-controlled period

Title

Part 2: Percentage of Participants With Treatment Discontinuation Due to Adverse Events (AEs) and Serious Adverse Events (SAEs) in the Placebo-Controlled Period

Description

Time Frame

Day 1 up to 12 months of the placebo-controlled period

Title

Part 2: Number of Participants Aged 6-25 Years With Suicidal Ideation Based on Columbia-Suicide Severity Rating Scale (C-SSRS) in the Placebo-Controlled Period

Description

Time Frame

Day 1 up to 12 months of the placebo-controlled period

Title

Part 2: Number of Participants Aged 6-25 Years With Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) in the Placebo-Controlled Period

Description

Time Frame

Day 1 up to 12 months of the placebo-controlled period

Title

Survival of Motor Neuron 2 (SMN2) Messenger Ribonucleic Acid (mRNA) Levels in Blood

Time Frame

Part 2: Days -1, 1, 7, 28, 120, 246, 365, 729

Title

Survival of Motor Neuron (SMN) Protein Levels in Blood

Time Frame

Part 2: Days -1, 7, 28, 120, 246, 365, 729

Title

Part 1 and 2: Maximum Plasma Concentration (Cmax) of Risdiplam

Time Frame

Part 1 and 2: 1, 2, 4, 6 hours post dose on Day 1; Pre-dose (Hour 0) on Days 7, 14, 56 (Part 2), 120, 246, 490, 729; pre-dose (Hour 0) and 1, 2, 4, 6 hours post dose on Days 28, 56 (Part 1), 365, 609

Title

Part 1 and 2: Area Under the Curve (AUC) of Risdiplam

Time Frame

Part 1 and 2: 1, 2, 4, 6 hours post dose on Day 1; Pre-dose (Hour 0) on Days 7, 14, 56 (Part 2), 120, 246, 490, 729; pre-dose (Hour 0) and 1, 2, 4, 6 hours post dose on Days 28, 56 (Part 1), 365, 609

Title

Part 1 and 2: Concentration at the End of a Dosing Interval (Ctrough) of Risdiplam

Time Frame

Part 1 and 2: Pre-dose (Hour 0) on Days 7, 14, 28, 56, 120, 246, 365, 490, 609, 729

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

25 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Confirmed diagnosis of 5q-autosomal recessive SMA Negative blood pregnancy test at screening and agreement to comply with measures to prevent pregnancy and restrictions on sperm donation For Part 1: Type 2 or 3 SMA ambulant or non-ambulant For Part 2: 1) Type 2 or 3 SMA non-ambulant; 2) RULM entry item A greater than or equal to 2; 3) ability to sit independently as assessed by item 9 of the MFM Exclusion Criteria: 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 Concomitant or previous administration of a SMN2-targeting antisense oligonucleotide, SMN2 splicing modifier or gene therapy either in a clinical study or as part of medical care Any history of cell therapy Hospitalization for a pulmonary event within the last 2 months or planned at time of screening Surgery for scoliosis or hip fixation in the one year preceding screening or planned within the next 18 months Unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular system diseases as considered to be clinically significant by the Investigator Presence of clinically significant electrocardiogram abnormalities before study drug administration from average of triplicate measurement or cardiovascular disease indicating a safety risk for participants as determined by the Investigator Any major illness within one month before the screening examination or any febrile illness within one week prior to screening and up to first dose administration Recently initiated treatment (within less than [<] 6 months prior to randomization) with oral salbutamol or another beta 2-adrenergic agonist taken orally Any prior use of chloroquine, hydroxychloroquine, retigabin, vigabatrin or thioridazine, is not allowed Ascertained or presumptive hypersensitivity (e.g., anaphylactic reaction) to Risdiplam or to the constituents of its formulation Recent history (less than one year) of ophthalmological diseases Participants requiring invasive ventilation or tracheostomy

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

Stanford University Medical Center

City

Palo Alto

State/Province

California

ZIP/Postal Code

94304

Country

United States

Facility Name

Columbia University Medical Center; The Neurological Institute of New York

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

UZ Gent

City

Gent

ZIP/Postal Code

9000

Country

Belgium

Facility Name

UZ Leuven Gasthuisberg

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Chr de La Citadelle

City

Liège

ZIP/Postal Code

4000

Country

Belgium

Facility Name

Instituto de Puericultura E Pediatria Martagão Gesteira

City

Rio de Janeiro

State/Province

ZIP/Postal Code

CEP 21941-912

Country

Brazil

Facility Name

Alberta Children's Hospital Division of Pediatric Neurology

City

Calgary

State/Province

Alberta

ZIP/Postal Code

T3B 6A8

Country

Canada

Facility Name

London Health Sciences Centre; Children's Hospital; Pediatrics

City

London

State/Province

Ontario

ZIP/Postal Code

N6A 5W9

Country

Canada

Facility Name

McGill University Health Centre - Glen Site

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H4A 3J1

Country

Canada

Facility Name

Peking University First Hospital

City

Beijing City

ZIP/Postal Code

100034

Country

China

Facility Name

Children's Hospital of Fudan University

City

Shanghai

ZIP/Postal Code

201102

Country

China

Facility Name

Clinical Medical Center Zagreb; University Hospital Rebro Department of Paediatrics

City

Zagreb

ZIP/Postal Code

10000

Country

Croatia

Facility Name

Hopital Femme Mere Enfant; Medecine Physique et Readaptation Pediatrique ? L?ESCALE

City

Bron

ZIP/Postal Code

69677

Country

France

Facility Name

Hopital Roger Salengro

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

CHU de Nantes - Hotel Dieu

City

Nantes

ZIP/Postal Code

44093

Country

France

Facility Name

Hôpital Necker-Enfants Malades; Service de neuropédiatrie

City

Paris

ZIP/Postal Code

75015

Country

France

Facility Name

Hopital Armand Trousseau

City

Paris

ZIP/Postal Code

75571

Country

France

Facility Name

Universitätsklinikum Freiburg; Klinik für Neuropädiatrie und Muskelerkrankungen

City

Freiburg

ZIP/Postal Code

79106

Country

Germany

Facility Name

IRCCS Ospedale Pediatrico Bambino Gesù; U.O. Malattie Neuromuscolari e Neurodegenerative

City

Roma

State/Province

Lazio

ZIP/Postal Code

00165

Country

Italy

Facility Name

Policlinico Agostino Gemelli; Dipartimento di Neuropsichiatria Infantile

City

Roma

State/Province

Lazio

ZIP/Postal Code

00168

Country

Italy

Facility Name

IRCCS Istituto Giannina Gaslini; U.O.S.D. Centro di Miologia e Patologie Neurodegenerative

City

Genova

State/Province

Liguria

ZIP/Postal Code

16147

Country

Italy

Facility Name

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Unità Operativa Complessa di Neurologia

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20122

Country

Italy

Facility Name

Fondazione IRCCS Istituto Neurologico ?Carlo Besta?; UO di Neurologia dello Sviluppo

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20133

Country

Italy

Facility Name

Fukuoka Children's Hospital

City

Fukuoka

ZIP/Postal Code

813-0017

Country

Japan

Facility Name

Hiroshima University Hospital

City

Hiroshima

ZIP/Postal Code

734-8551

Country

Japan

Facility Name

Hyogo Medical University Hospital

City

Hyogo

ZIP/Postal Code

663-8501

Country

Japan

Facility Name

Minami Kyushu National Hospital

City

Kagoshima

ZIP/Postal Code

899-5293

Country

Japan

Facility Name

Miyagi Children's Hospital

City

Miyagi

ZIP/Postal Code

989-3126

Country

Japan

Facility Name

Shiga Medical Center for Children

City

Shiga

ZIP/Postal Code

524-0022

Country

Japan

Facility Name

Shizuoka Children's Hospital

City

Shizuoka

ZIP/Postal Code

420-8660

Country

Japan

Facility Name

Jichi Medical University Hospital

City

Tochigi

ZIP/Postal Code

329-0498

Country

Japan

Facility Name

Center Hospital of the National Center for Global Health and Medicine

City

Tokyo

ZIP/Postal Code

162-0052

Country

Japan

Facility Name

National Center Of Neurology And Psychiatry Hospital

City

Tokyo

ZIP/Postal Code

187-8551

Country

Japan

Facility Name

Szpital Gdanskiego Uniwersytetu Medycznego; Clinic of developmental neurology

City

Gda?sk

ZIP/Postal Code

80-952

Country

Poland

Facility Name

Uniwersytecki Szpital Kliniczny w Poznaniu; Od. Kliniczny Neurologii Dzieci i M?odziezy

City

Pozna?

ZIP/Postal Code

60-355

Country

Poland

Facility Name

Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie

City

Warszawa

ZIP/Postal Code

02-097

Country

Poland

Facility Name

Russian Children Neuromuscular Center of Veltischev

City

Moscow

State/Province

Moskovskaja Oblast

ZIP/Postal Code

125412

Country

Russian Federation

Facility Name

Clinic for Neurology and Psychiatry for Children and Youth

City

Belgrade

ZIP/Postal Code

11000

Country

Serbia

Facility Name

Hospital Sant Joan De Deu

City

Esplugues De Llobregas

State/Province

Barcelona

ZIP/Postal Code

08950

Country

Spain

Facility Name

Hospital Universitari Vall d'Hebron; Servicio de Reumatologia

City

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Hospital Universitario La Paz

City

Madrid

ZIP/Postal Code

280146

Country

Spain

Facility Name

Hospital Universitario Virgen del Rocío

City

Sevilla

ZIP/Postal Code

41013

Country

Spain

Facility Name

Hacettepe University, School of Medicine; Pediatrics Department; Pediatrics Child Neurology Unit

City

Ankara

ZIP/Postal Code

06100

Country

Turkey

Facility Name

Hospital Yeditepe University Kozyatagi; Pediatry

City

Atasehir- Istanbul

ZIP/Postal Code

34752

Country

Turkey

Facility Name

University of Oxford; Department of Paediatrics

City

Headington

ZIP/Postal Code

OX3 9DU

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

34942136

Citation

Mercuri E, Deconinck N, Mazzone ES, Nascimento A, Oskoui M, Saito K, Vuillerot C, Baranello G, Boespflug-Tanguy O, Goemans N, Kirschner J, Kostera-Pruszczyk A, Servais L, Gerber M, Gorni K, Khwaja O, Kletzl H, Scalco RS, Staunton H, Yeung WY, Martin C, Fontoura P, Day JW; SUNFISH Study Group. Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2022 Jan;21(1):42-52. doi: 10.1016/S1474-4422(21)00367-7. Erratum In: Lancet Neurol. 2022 Feb;21(2):e2. Lancet Neurol. 2022 Mar;21(3):e3. Lancet Neurol. 2022 May;21(5):e5.

Results Reference

derived

Links:

URL

http://roche-sma-clinicaltrials.com

Description

roche-sma-clinicaltrials.com provides information about the Roche Sunfish clinical trial NCT02908685 and molecule being investigated in SMA.

Learn more about this trial

A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Risdiplam (RO7034067) in Type 2 and 3 Spinal Muscular Atrophy (SMA) Participants

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