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

NCT ID: NCT05115110

Last Updated: 2025-12-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 259 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-02
• Study Completion Date: 2029-02-27

Brief Summary

Risdiplam works by helping the body produce more survival motor neuron (SMN) protein throughout the body. This means fewer motor neurons - nerve cells that pass impulses from nerves to muscles to cause movement - are lost, which may improve how well muscles work in people with SMA. RO7204239 is an investigational anti-myostatin antibody that is designed to target myostatin. Myostatin plays an important role in the regulation of skeletal muscle size by controlling growth. Inhibiting myostatin may help muscles grow in size and strength. RO7204239 in combination with risdiplam, which is designed to increase the amount of SMN protein throughout the body, has the potential to further improve motor function and clinical outcomes for people living with SMA.

This trial will study the safety and efficacy of RO7204239 in combination with risdiplam in patients with spinal muscular atrophy (SMA). The trial has two parts; Part 1 is the dose-finding part in SMA patients that are either ambulant (aged 2-10 years) or non-ambulant (aged 5-10 years) within separate cohorts, and Part 2 is the pivotal part in SMA patients aged 2-25 years that are ambulant.

Conditions

Spinal Muscular Atrophy (SMA)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

RO7204239

Intervention Type: DRUG

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.

Risdiplam

Intervention Type: DRUG

Risdiplam will be administered orally once daily (QD) for the duration of the study.

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.

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be administered Q4W by SC injection into the abdomen.

Risdiplam

Intervention Type: DRUG

Risdiplam will be administered orally once daily (QD) for the duration of the study.

Interventions

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.

Intervention Type: DRUG

Placebo

Placebo will be administered Q4W by SC injection into the abdomen.

Intervention Type: DRUG

Risdiplam

Risdiplam will be administered orally once daily (QD) for the duration of the study.

Intervention Type: DRUG

Other Intervention Names

RO7034067; Evrysdi

Eligibility Criteria

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

• 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

• 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

• 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

• 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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Nemours Children's Hospital

Orlando, Florida, United States

Boston Childrens Hospital

Boston, Massachusetts, United States

Columbia University Medical Center

New York, New York, United States

Neurology & Neuromuscular Care Center

Denton, Texas, United States

Sydney Children's Hospital

Randwick, New South Wales, Australia

UZ Gent

Ghent, , Belgium

Chr de La Citadelle

Liège, , Belgium

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

The Hospital for Sick Children

Toronto, Ontario, Canada

McGill University Health Centre - Glen Site

Montreal, Quebec, Canada

Clinical Hospital Centre Zagreb

Zagreb, , Croatia

Ospedale Pediatrico Bambino Gesù

Rome, Lazio, Italy

Policlinico Agostino Gemelli

Rome, Lazio, Italy

IRCCS Istituto Giannina Gaslini

Genoa, Liguria, Italy

Fondazione IRCCS Istituto Neurologico ?Carlo Besta?

Milan, Lombardy, Italy

Asst Grande Ospedale Metropolitano Niguarda

Milan, Lombardy, Italy

Ospedali Riuniti Torrette di Ancona

Ancona, The Marches, Italy

Kobe University Hospital

Hyōgo, , Japan

Kagoshima University Hospital

Kagoshima, , Japan

National Center for Global Health and Medicine

Tokyo, , Japan

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Instytut Centrum Zdrowia Matki Polki

Lodz, , Poland

Uniwersytecki Szpital Kliniczny w Poznaniu

Poznan, , Poland

Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie

Warsaw, , Poland

Instytut Pomnik Centrum Zdrowia Dziecka

Warsaw, , Poland

CHULC, E.P.E. - Hospital Dona Estefania

Lisbon, , Portugal

Hospital de Santa Maria

Lisbon, , Portugal

Hospital Sant Joan De Deu

Esplugues de Llobregas, Barcelona, Spain

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario la Fe

Valencia, , Spain

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Great Ormond Street Hospital For Children

London, , United Kingdom

John Radcliffe Hospital

Oxford, , United Kingdom

Countries

United States; Australia; Belgium; Canada; Croatia; Italy; Japan; Netherlands; Poland; Portugal; Spain; United Kingdom

Other Identifiers

2023-506761-65-00

Identifier Type: OTHER

Identifier Source: secondary_id

BN42644

Identifier Type: -

Identifier Source: org_study_id