A clinical trial to look at how well RO7204239 plus risdiplam works to improve muscle control in children with spinal muscular atrophy, and how safe this drug combination is

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

  • Spinal Muscular Atrophy (SMA)
Trial Status:

Recruiting

This trial runs in
Countries
  • Belgium
  • Germany
  • Italy
  • Poland
Trial Identifier:

NCT05115110 BN42644

      Show trial locations

      The source of the below information is the publicly available website ClinicalTrials.gov. It has been summarised and edited into simpler language.

      The below information is taken directly from the publicly available website ClinicalTrials.gov within a week of any updates, and has not been edited.

      Results Disclaimer

      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. 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 children aged 2-10 years with spinal muscular atrophy (SMA) that are ambulant.

      Hoffmann-La Roche Sponsor
      Phase 2/Phase 3 Phase
      NCT05115110 , BN42644 Trial Identifier
      All Gender
      ≥2 Years & ≤ 10 Years Age
      No Healthy Volunteers

       

      How does the MANATEE clinical trial work?

      This clinical trial is recruiting children aged 2–10 years old with spinal muscular atrophy (SMA) who are ambulant (able to walk independently).

      The purpose of this clinical trial is to compare the effects, good or bad, of RO7204239 plus risdiplam versus placebo plus risdiplam in children with SMA. If your child takes part in this clinical trial, they will receive either RO7204239 plus risdiplam or placebo plus risdiplam. All participants in the clinical trial will receive a daily dose of risdiplam at the approved dose throughout the clinical trial, including those in the placebo group.

      This clinical trial is split into two parts. Part 1 will begin first and will study the safety of RO7204239 plus risdiplam and determine the right dose of RO7204239 to use. Part 2 will use the RO7204239 dose selected during Part 1 and will study how well it works when combined with risdiplam, as well as the safety of the combination in a larger number of patients. Your child will only be enrolled into one part of this clinical trial.

       

      How does my child take part in this clinical trial?

      To be able to take part in this clinical trial, your child must be 2–10 years old, have been diagnosed with SMA and be ambulant (able to walk or run independently). Patients who have previously been treated with either risdiplam, nusinersen or onasemnogene abeparvovec are eligible to take part in this clinical trial, as well as those who have not received treatment before. For patients previously treated with nusinersen or onasemnogene abeparvovec, the last dose should be at least 90 days before screening.

      Your child must not have previously received anti-myostatin treatments or cell therapies. If your child has certain other medical conditions or is taking specific treatments (e.g. another anti-myostatin treatment, or cell therapies), they may not be able to take part in this clinical trial.

      If after reading this document, you think this clinical trial may be suitable for your child and would like to take part, please talk to your doctor. If your doctor thinks that your child might be able to take part in this clinical trial, they may refer you to the closest clinical trial doctor. They will give you all the information you need to make your decision about taking part in the clinical trial. You can also find the clinical trial locations on this page.

      Your child will have some further tests to make sure they will be able to take the treatments given in this clinical trial. Some of these tests or procedures (e.g. physical examination) may be part of your child’s regular medical care and may therefore be done even if your child does not take part in the clinical trial. If your child has had some of the tests recently, they may not need to be done again.

      Before starting the clinical trial, you and your child will be told about any risks and benefits of taking part in the trial. You will also be told what other treatments are available so that you may decide if you still want your child to take part.

      What treatment will my child be given if they join this clinical trial?

      Everyone who joins this clinical trial will receive a daily dose of risdiplam at the approved dose throughout the trial. In addition, your child will be split into two treatment groups randomly (this is why it is called a randomised trial) to be given either:

      • RO7204239 as an injection under the skin (subcutaneous) at the hospital every four weeks, as well as risdiplam as a liquid to be swallowed at home once every day
      • OR placebo (medicine with no active ingredients) as an injection under the skin (subcutaneous) at the hospital every four weeks, as well as risdiplam as a liquid to be swallowed at home once every day.

      This is a ‘placebo-controlled’ clinical trial, which means that in addition to risdiplam, one of the groups will be given a placebo. A placebo is used to show the effects of the combination of RO7204239 with risdiplam compared to the effect of treatment with only risdiplam.

      Children who have not previously been treated with risdiplam for at least eight continuous weeks before joining this clinical trial will receive risdiplam for at least eight weeks before starting the clinical trial treatment.

      Risdiplam works by helping the body produce more survival motor neuron protein throughout the body. This means fewer motor neurons (which pass impulses from the nerves to muscles, causing movement) are lost, which may improve how well muscles work in people with SMA. RO7204239 works by decreasing the amount of myostatin protein in the body; the myostatin protein typically reduces muscle growth and development. The combination of RO7204239 with risdiplam may have a combined effect to improve muscle function in children with SMA.

      If your child is enrolled in Part 1 of the clinical trial, they will have a 67% (2 out of 3) chance of receiving RO7204239 and risdiplam, and a 33% (1 out of 3) chance of receiving placebo and risdiplam. During this time, neither you, your child, nor their clinical trial doctor can choose or know the group they are in. However, the clinical trial doctor can find out which treatment your child is receiving if their safety is at risk. After 24 weeks (approximately six months), if your child originally received placebo and risdiplam, they will switch treatments to receive RO7204239 and risdiplam. When your child has completed 72 weeks (approximately 18 months) of RO7204239 and risdiplam, they may continue treatment by participating in the open-label extension of the clinical trial for up to two more years.

      If your child is enrolled in Part 2, they will receive treatment for 72 weeks (approximately 18 months), and they will have an equal chance of receiving RO7204239 plus risdiplam or placebo plus risdiplam. During this time, neither you, your child, nor their clinical trial doctor can choose or know the group they are in. However, the clinical trial doctor can find out which group your child is in if their safety is at risk.

      How often will my child be seen in follow-up appointments and for how long?

      Injections of RO7204239 or placebo will be given at the hospital by a member of the clinical trial team every four weeks. Your child will be monitored at the site for at least six hours after the first two injections, and for two hours after the remaining injections. Risdiplam will be given at the approved dose as a liquid to swallow at home once daily.

      During the clinical trial, your child will be seen regularly by the clinical trial doctor. These hospital visits will include checks to see how your child is responding to the treatment and any side effects that they may be having.

      Your child is free to stop this treatment at any time. After stopping treatment, your child will have a follow-up appointment with the clinical trial doctor three months after their last dose.

       

      What happens if my child is unable to take part in this clinical trial?

      If this clinical trial is not suitable for your child, they will not be able to take part. Your doctor may suggest other clinical trials that your child may be able to take part in or other treatments that they can be given. Your child will not lose access to any of their regular care.

      For more information about this clinical trial see the For Expert tab on the specific ForPatients page or follow this link to ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT05115110

      Trial-identifier: NCT05115110

      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. 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 children aged 2-10 years with spinal muscular atrophy (SMA) that are ambulant.

      Hoffmann-La Roche Sponsor
      Phase 2/Phase 3 Phase
      NCT05115110 , BN42644 Trial Identifier
      RO7204239, Placebo, Risdiplam Treatments
      Spinal Muscular Atrophy (SMA) Condition
      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 Ambulant Patients With Spinal Muscular Atrophy

      Eligibility Criteria

      All Gender
      ≥2 Years & ≤ 10 Years Age
      No Healthy Volunteers
      Inclusion Criteria
      • Participants who are 2 to 10 years of age inclusive at screening
      • Participants who have a confirmed genetic diagnosis of 5q-autosomal recessive SMA
      • Symptomatic SMA disease, as per investigator's clinical judgement
      • 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 as measured by the Timed 10-Meter Walk/Run Test [10MWRT] seconds at screening
      • 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
      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
      • For Part 1 participants aged 5 to 10 years only: contraindications for MRI scans including difficulties maintaining a prolonged supine position, or any other clinical history or examination finding that would pose a potential hazard in combination with MRI
      • 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

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