A Study to Investigate the Safety and Efficacy of RO7204239 in Combination With Risdiplam (RO7034067) in Participants With Spinal Muscular Atrophy

Recruitment Status
ACTIVE, NOT RECRUITING
(See Contacts and Locations)Verified February 2026 by Hoffmann-La Roche
Sponsor
Hoffmann-La Roche
Information Provided by (Responsible Party)
Hoffmann-La Roche
Clinicaltrials.gov Identifier
NCT05115110
Other Study ID Numbers:
BN42644
First Submitted
October 31, 2021
First Posted
November 9, 2021
Last Update Posted
March 12, 2026
Last Verified
February 2026

ClinicalTrials.gov processed this data on March 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Spinal Muscular Atrophy (SMA)
Drug: RO7204239Drug: Placebo

Study Design

Study TypeInterventional
Actual Enrollment259 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingDouble
Primary PurposeTreatment
Official TitleA 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
Study Start DateJune 1, 2022
Actual Primary Completion Date2yrs 9mos from now
Actual Study Completion Date2yrs 9mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
RO7204239 + Risdiplam
Participants who have not previously been treated with risdiplam will receive risdiplam for at least 8 weeks prior to randomization into a treatment group (Part 1 only). Participants that have been treated with risdiplam for at least 8 continuous weeks immediately prior to joining the study may be immediately randomized to combination therapy, or join the study run-in period (the period between screening and randomization to a treatment group) where they will continue to receive risdiplam monotherapy until randomization. Participants enrolled in Part 1 will receive RO7204239 (low or high dose) + risdiplam for 24 weeks, followed by RO7204239 + risdiplam for 72 weeks. Participants enrolled in Part 2 will receive risdiplam for 8 weeks and then treatment with RO7204239 + risdiplam for 72 weeks. Once the treatment period has completed (Part 1 or Part 2), participants will have the option of treatment with RO7204239 + risdiplam for 2 additional years.
Drug: RO7204239
RO7204239 will administered every 4 weeks (Q4W) by subcutaneous (SC) injection into the abdomen. RO7204239 will be investigated at low- and high-dose in Part 1.
Placebo + Risdiplam
Participants who have not previously been treated with risdiplam will receive risdiplam for at least 8 weeks prior to randomization into a treatment group (Part 1 only). Participants that have been treated with risdiplam for at least 8 continuous weeks immediately prior to joining the study may be immediately randomized to combination therapy, or join the study run-in period (the period between screening and randomization to a treatment group) where they will continue to receive risdiplam monotherapy until randomization. Participants enrolled in Part 1 will receive placebo (low or high dose-matched) + risdiplam for 24 weeks, followed by RO7204239 + risdiplam for 72 weeks. Participants enrolled in Part 2 will receive risdiplam for 8 weeks and then treatment with placebo + risdiplam for 72 weeks. Once the treatment period has completed (Part 1 or Part 2), participants will have the option of treatment with RO7204239 + risdiplam for 2 additional years.
Drug: Placebo
Placebo will be administered Q4W by SC injection into the abdomen.

Outcome Measures

Primary Outcome Measures
  1. Part 1 - Percentage of participants with adverse events (AEs)
  2. Part 1 - Incidence of relevant echocardiographic parameter z scores > 2
  3. Part 1 - Serum concentration of RO7204239
  4. Part 1 - Time to maximum serum concentration (Cmax) of RO7204239
  5. Part 1 - Area under the curve (AUC) of RO7204239
  6. Part 1 - Trough concentration (Ctrough) of RO7204239
  7. Part 1 - Plasma concentration of risdiplam
  8. Part 1 - Plasma concentration of risdiplam metabolite (M1)
  9. Part 1 - Cmax of risdiplam
  10. Part 1 - AUC of risdiplam
  11. Part 1 - Ctrough of risdiplam
  12. Part 1 - Incidence of anti-drug antibodies (ADAs)
  13. Part 1 - Change from baseline in serum concentration of total myostatin
  14. Part 1 - Change from baseline in serum concentration of free latent myostatin
  15. Part 1 - Change from baseline in serum concentration of mature myostatin
  16. Part 1 - Percent change from baseline in the contractile area of skeletal muscle in the dominant thigh muscles as assessed by magnetic resonance imaging (MRI) in participants aged at least 5 years
  17. Part 1 - Percent change from baseline in the contractile area of skeletal muscle in the dominant calf muscles as assessed by MRI in participants aged at least 5 years
  18. Part 2 - Change from baseline in Revised Hammersmith Scale (RHS) total score
Secondary Outcome Measures
  1. Part 2 - Change from baseline in Motor Function Measure (MFM) Domain 1 + Domain 2 (D1 + D2) score
  2. Part 2 - Change from baseline in MFM-32 total score
  3. Part 2 - Change from baseline in time taken to rise from the floor as measured by RHS Item 25
  4. Part 2 - Change from baseline in time taken to walk/run 10 meters as measured by RHS Item 19
  5. Part 2 - Percent change from baseline in lean mass as assessed by full body dual energy X-ray absorptiometry (DXA) scan in participants aged at least 5 years
  6. Part 2 - Percentage of participants with adverse events (AEs)
  7. Part 2 - Serum concentration of RO7204239
  8. Part 2 - Cmax of RO7204239
  9. Part 2 - AUC of RO7204239
  10. Part 2 - Ctrough of RO7204239
  11. Part 2 - Plasma concentration of risdiplam
  12. Part 2 - Plasma concentration of risdiplam metabolite (M1)
  13. Part 2 - Cmax of risdiplam
  14. Part 2 - AUC of risdiplam
  15. Part 2 - Ctrough of risdiplam
  16. Part 2 - Incidence of ADAs

Eligibility Criteria

Ages Eligible for Study(Child, Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
Age at screening: Part 1 Cohorts A (ambulant participants), B (ambulant participants), and D (non-ambulant participants): 5-10 years, inclusive; Part 1 Cohort C (ambulant participants): 2-4 years, inclusive; Part 2 (ambulant participants): 2-25 years, inclusive
Participants who have a confirmed genetic diagnosis of 5q-autosomal recessive SMA
Symptomatic SMA disease, as per investigator's clinical judgement
Participants who have received previous SMA disease-modifying therapies may be included provided that: 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, coagulatory 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; Nusinersen last dose was received at least 90 days prior to screening; Risdiplam is switched to the investigational medicinal product (IMP) provided by the site Inclusion Criteria 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 measures by the Timed 10-Meter Walk/Run Test \[10MWRT\] at screening Inclusion Criteria for Part 1 Cohort D only:
Participants who are able to sit, defined by: A score of 3 on Item 9 of the MFM32 (sitting without upper limb support while maintaining contact between the two hands for 5 seconds); A score of at least 2 on Item 10 of the MFM32 (while seated, leaning forward to touch a tennis ball and sitting back again, either with or without upper limb support)
Participants who are able to raise a standardized plastic cup with a 200g 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)
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, with the exception of those who have completed a risdiplam study, or participated in a nusinersen or onasemnogene abeparvovec study
Receiving or have received previous administration of anti-myostatin therapies
Any history of cell therapy
Hospitalization for a pulmonary event within the last 2 months or planned hospitalization at the time of screening
Past 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 ECG abnormalities at screening from average of triplicate measurement, abnormal findings at echocardiography, or cardiovascular disease indicating a safety risk for participants at the time of screening
Any major illness within 1 month before screening
Received any multidrug and toxin extrusion (MATE1/2K) substrates within 2 weeks before screening
Hereditary fructose intolerance
Used 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 at the time of screening
Ascertained or presumptive hypersensitivity to RO7204239 or risdiplam, or to the constituents of its formulations
Clinically relevant history of anaphylactic reaction requiring inotropic support
Any abnormal skin conditions, pigmentation or lesions in the area intended for 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 Exclusion Criteria for Part 1 Cohorts A and B only:
Participants with contraindications for MRI scan (including, but not restricted to, claustrophobia, pacemaker, artificial heart valves, cochlear implants, presence of foreign metal objects in heart or body, including spinal rods, intracranial vascular clips, insulin pumps, etc.), difficulties maintaining a prolonged supine position, or any other clinical history or examination finding that would pose a potential hazard in combination with MRI Exclusion Criteria for Part 1 Cohort D only:
Participants who are unable to adopt the correct position to endure adequate quality of DXA scan acquisition, as determined by the DXA scan technologist
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
For participants able to take steps only: Able to walk 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 10MWRT at screening
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 (e.g., in participants with mild scoliosis)
Participants who require invasive ventilation, tracheostomy, or the use of noninvasive ventilation (e.g., bilevel positive airway pressure) during the daytime

Contacts and Locations

Sponsors and CollaboratorsHoffmann-La Roche
Locations
Nemours Children's Hospital | Orlando Florida, United States, 32827Boston Childrens Hospital | Boston Massachusetts, United States, 02115Columbia University Medical Center | New York New York, United States, 10032Neurology & Neuromuscular Care Center | Flower Mound Texas, United States, 75028Sydney Children's Hospital | Randwick New South Wales, Australia, 2031UZ Gent | Ghent , Belgium, 9000Chr de La Citadelle | Liège , Belgium, 4000British Columbia Children's Hospital | Vancouver British Columbia, Canada, V6H 3N1The Hospital for Sick Children | Toronto Ontario, Canada, M5G 1X8McGill University Health Centre - Glen Site | Montreal Quebec, Canada, H4A 3J1Clinical Hospital Centre Zagreb | Zagreb , Croatia, 10000Ospedale Pediatrico Bambino Gesù | Rome Lazio, Italy, 00165Policlinico Agostino Gemelli | Rome Lazio, Italy, 00168IRCCS Istituto Giannina Gaslini | Genoa Liguria, Italy, 16147Fondazione IRCCS Istituto Neurologico ?Carlo Besta? | Milan Lombardy, Italy, 20133Asst Grande Ospedale Metropolitano Niguarda | Milan Lombardy, Italy, 20162Ospedali Riuniti Torrette di Ancona | Ancona The Marches, Italy, 60126Kobe University Hospital | Hyōgo , Japan, 650-0017Kagoshima University Hospital | Kagoshima , Japan, 890-8520National Center for Global Health and Medicine | Tokyo , Japan, 162-0052Universitair Medisch Centrum Utrecht | Utrecht , Netherlands, 3584 CXInstytut Centrum Zdrowia Matki Polki | ?ód? , Poland, 93-338Uniwersyteckie Centrum Kliniczne | Gda?sk , Poland, 80-952Uniwersytecki Szpital Kliniczny w Poznaniu | Późna , Poland, 60-355Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie | Warsaw , Poland, 02-097Instytut Pomnik Centrum Zdrowia Dziecka | Warsaw , Poland, 04-730CHULC, E.P.E. - Hospital Dona Estefania | Lisbon , Portugal, 1169-045Hospital de Santa Maria | Lisbon , Portugal, 1649-035Hospital Sant Joan De Deu | Esplugues de Llobregas Barcelona, Spain, 08950Hospital Vall d'Hebron | Barcelona , Spain, 08035Hospital Universitario La Paz | Madrid , Spain, 28046Hospital Universitario la Fe | Valencia , Spain, 46026Birmingham Heartlands Hospital | Birmingham , United Kingdom, B9 5SSGreat Ormond Street Hospital For Children | London , United Kingdom, WC1N 3JHJohn Radcliffe Hospital | Oxford , United Kingdom, OX3 9DU
Investigators
Study Director: Clinical Trials, Hoffmann-La Roche