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Spinal Muscular Atrophy (SMA)Phase 2/3MANATEENCT05115110

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

A Phase 2/3 study testing RO7204239 and Risdiplam in people with Spinal Muscular Atrophy (SMA), run by Hoffmann-La Roche at 29 sites in 12 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 2 to 25 years
Conditions the study is for
Spinal Muscular Atrophy (SMA)
What is being tested?
RO7204239 and Risdiplam
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
97 participants
Where
29 sitesin 12 countries
Study dates
2 Jun 2022to 2 Nov 2026
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
  • 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)

Who cannot join

  • 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
Show all 22Show fewer
  • 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

Trial locations and contacts

29 sites in 12 countries.

29 sites in 12 countries

Poland5 sites

  • Instytut Centrum Zdrowia Matki Polki

    ?ód?, 93-338

  • Uniwersyteckie Centrum Kliniczne

    Gda?sk, 80-952

  • Uniwersytecki Szpital Kliniczny w Poznaniu

    Późna, 60-355

  • Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie

    Warsaw, 02-097

  • Instytut Pomnik Centrum Zdrowia Dziecka

    Warsaw, 04-730

Other trials in Poland

Italy4 sites

  • Ospedali Riuniti Torrette di Ancona

    Ancona, The Marches, 60126

  • Fondazione IRCCS Istituto Neurologico ?Carlo Besta?

    Milan, Lombardy, 20133

  • Asst Grande Ospedale Metropolitano Niguarda

    Milan, Lombardy, 20162

  • Policlinico Agostino Gemelli

    Rome, Lazio, 00168

Other trials in Italy

Canada3 sites

  • McGill University Health Centre - Glen Site

    Montreal, Quebec, H4A 3J1

  • The Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3N1

Other trials in Canada

Japan3 sites

  • Kobe University Hospital

    Hyōgo, 650-0017

  • Kagoshima University Hospital

    Kagoshima, 890-8520

  • National Center for Global Health and Medicine

    Shinjuku-ku, 162-8655

Other trials in Japan

Spain3 sites

  • Hospital Sant Joan De Deu

    Esplugues de Llobregas, Barcelona, 08950

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Universitario la Fe

    Valencia, 46026

Other trials in Spain

United States2 sites

  • Boston Childrens Hospital

    Boston, Massachusetts, 02115

  • Columbia University Medical Center

    New York, New York, 10032

Other trials in United States

Belgium2 sites

  • UZ Gent

    Ghent, 9000

  • Chr de La Citadelle

    Liège, 4000

Other trials in Belgium

Portugal2 sites

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

    Lisbon, 1169-045

  • Hospital de Santa Maria

    Lisbon, 1649-035

Other trials in Portugal

United Kingdom2 sites

  • Birmingham Heartlands Hospital

    Birmingham, B9 5SS

  • John Radcliffe Hospital

    Oxford, OX3 9DU

Other trials in United Kingdom

Australia1 site

  • Sydney Children's Hospital

    Randwick, New South Wales, 2031

Other trials in Australia

Croatia1 site

  • Clinical Hospital Centre Zagreb

    Zagreb, 10000

Other trials in Croatia

Netherlands1 site

  • Universitair Medisch Centrum Utrecht

    Utrecht, 3584 CX

Other trials in Netherlands

About this study

Official title: 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

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.

Being tested
RO7204239, Placebo, Risdiplam
Medical subject headings
Muscular Atrophy, Spinal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RO7204239Drug

    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.

  • PlaceboDrug

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

  • RisdiplamDrug

    Also called RO7034067, Evrysdi

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

Study groups in NCT05115110
Study groupRoleWhat they receive
RO7204239 + RisdiplamExperimentalParticipants 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.
Receives: Drug: RO7204239; Drug: Risdiplam
Placebo + RisdiplamActive comparatorParticipants 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.
Receives: Drug: Placebo; Drug: Risdiplam

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1 - Percentage of participants with adverse events (AEs)

    Measured: Up to 4.5 years

  2. Part 1 - Incidence of relevant echocardiographic parameter z scores > 2

    Measured: Up to 4.5 years

  3. Part 1 - Serum concentration of RO7204239

    Measured: Through Week 96

  4. Part 1 - Time to maximum serum concentration (Cmax) of RO7204239

    Measured: Through Week 96

  5. Part 1 - Area under the curve (AUC) of RO7204239

    Measured: Through Week 96

  6. Part 1 - Trough concentration (Ctrough) of RO7204239

    Measured: Through Week 96

  7. Part 1 - Plasma concentration of risdiplam

    Measured: Week 21

  8. Part 1 - Plasma concentration of risdiplam metabolite (M1)

    Measured: Week 21

  9. Part 1 - Cmax of risdiplam

    Measured: Week 21

  10. Part 1 - AUC of risdiplam

    Measured: Week 21

  11. Part 1 - Ctrough of risdiplam

    Measured: Week 21

  12. Part 1 - Incidence of anti-drug antibodies (ADAs)

    Measured: Through Week 96

  13. Part 1 - Change from baseline in serum concentration of total myostatin

    Measured: Through Week 85

  14. Part 1 - Change from baseline in serum concentration of free latent myostatin

    Measured: Through Week 85

  15. Part 1 - Change from baseline in serum concentration of mature myostatin

    Measured: Through Week 85

  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

    Measured: Week 24 of combination treatment

  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

    Measured: Week 24 of combination treatment

  18. Part 2 - Change from baseline in Revised Hammersmith Scale (RHS) total score

    Measured: Week 72 of combination treatment (study Week 80)

Secondary outcomes (16)

  1. Part 2 - Change from baseline in Motor Function Measure (MFM) Domain 1 + Domain 2 (D1 + D2) score

    Measured: Week 72 of combination treatment (study Week 80)

  2. Part 2 - Change from baseline in MFM-32 total score

    Measured: Week 72 of combination treatment (study Week 80)

  3. Part 2 - Change from baseline in time taken to rise from the floor as measured by RHS Item 25

    Measured: Week 72 of combination treatment (study Week 80)

  4. Part 2 - Change from baseline in time taken to walk/run 10 meters as measured by RHS Item 19

    Measured: Week 72 of combination treatment (study Week 80)

  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

    Measured: Week 72 of combination treatment (study Week 80)

  6. Part 2 - Percentage of participants with adverse events (AEs)

    Measured: Up to 4.5 years

  7. Part 2 - Serum concentration of RO7204239

    Measured: Through Week 80

  8. Part 2 - Cmax of RO7204239

    Measured: Through Week 80

  9. Part 2 - AUC of RO7204239

    Measured: Through Week 80

  10. Part 2 - Ctrough of RO7204239

    Measured: Through Week 80

  11. Part 2 - Plasma concentration of risdiplam

    Measured: Week 32

  12. Part 2 - Plasma concentration of risdiplam metabolite (M1)

    Measured: Week 32

  13. Part 2 - Cmax of risdiplam

    Measured: Week 32

  14. Part 2 - AUC of risdiplam

    Measured: Week 32

  15. Part 2 - Ctrough of risdiplam

    Measured: Week 32

  16. Part 2 - Incidence of ADAs

    Measured: Through Week 80

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Nov 2021
  2. Study start2 Jun 2022
  3. Primary completion2 Nov 2026
  4. Study completion2 Nov 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
97 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05115110
Sponsor's protocol ID
BN42644
Other IDs
2023-506761-65-00, 2023
Acronym
MANATEE
Status last verified
Nov 2026
First submitted
1 Nov 2021
Last updated
4 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing RO7204239 and Risdiplam in people with Spinal Muscular Atrophy (SMA), run by Hoffmann-La Roche at 29 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in Poland, Italy, Canada, Japan, Spain and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1 - Percentage of participants with adverse events (AEs) (time frame: Up to 4.5 years). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05115110.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.

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