Risdiplam for Muscular Atrophy

Phase-Based Estimates
1
Effectiveness
2
Safety
Clinic for Neurology and Psychiatry for Children and Youth, Belgrade, Serbia
Muscular Atrophy+2 More
Risdiplam - Drug
Eligibility
< 65
All Sexes
Eligible conditions
Muscular Atrophy

Study Summary

This study is evaluating whether a drug called Risdiplam can improve muscle function in people with spinal muscular atrophy.

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Eligible Conditions

  • Muscular Atrophy
  • Muscular Atrophy, Spinal
  • Atrophy

Treatment Effectiveness

Effectiveness Estimate

1 of 3

Compared to trials

Study Objectives

This trial is evaluating whether Risdiplam will improve 3 primary outcomes and 32 secondary outcomes in patients with Muscular Atrophy. Measurement will happen over the course of Day 1 on risdiplam up to end of study (up to approximately 7 years).

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
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
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
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
Part 2: Percentage of Participants With Marked Improvement (Defined as >= 3) in the Total Motor Function Measure (MFM32) Score at Month 12
Month 12
Part 2: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Month 12 in Participants Aged 6-25 Years
Part 2: Change From Baseline in Forced Vital Capacity (FVC) at Month 12 in Participants Aged 6-25 Years
Part 2: Change From Baseline in Maximal Expiratory Pressure (MEP) at Month 12 in Participants Aged 6-25 Years
Part 2: Change From Baseline in Maximal Inspiratory Pressure (MIP) at Month 12 in Participants Aged 6-25 Years
Part 2: Change From Baseline in Total Score of Hammersmith Functional Motor Scale Expanded (HFMSE) at Month 12
Part 2: Change From Baseline in the Best Sniff Nasal Inspiratory Pressure (SNIP) at Month 12
Part 2: Change From Baseline in the Caregiver-Reported SMA Independence Scale (SMAIS) Total Score at Month 12
Part 2: Change From Baseline in the MFM-32 Domain 1 (D1) Score at Month 12
Part 2: Change From Baseline in the MFM-32 Domain 2 (D2) Score at Month 12
Part 2: Change From Baseline in the MFM-32 Domain 3 (D3) Score at Month 12
Part 2: Change From Baseline in the Participant-Reported SMA Independence Scale (SMAIS) Total Score at Month 12
Part 2: Change From Baseline in the Peak Cough Flow (PCF) at Month 12 in Participants Aged 6-25 Years
Part 2: Change From Baseline in the Total Combined Scores of MFM-32 Domains 1 and 2 at Month 12
Part 2: Change From Baseline in the Total Combined Scores of MFM-32 Domains 2 and 3 at Month 12
Part 2: Change From Baseline in the Total Motor Function Measure 32 (MFM-32) Total Score at Month 12
Part 2: Change From Baseline in the Total Score of the Revised Upper Limb Module (RULM) at Month 12
Month 12
Part 2: Number of Disease-related Adverse Events Per Patient-years at Month 12
Part 2: Percentage of Participants Who Experience at Least One Disease-Related Adverse Event at Month 12
Year 7
Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Month 12
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
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
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
Week 4
Part 1: Selected Part 2 Dose of Risdiplam for Participants With BW of <20kg
Part 1: Selected Part 2 Dose of Risdiplam for Participants With a Body Weight (BW) of >/=20kg
Day 28
Part 1 and 2: Area Under the Curve (AUC) of Risdiplam
Part 1 and 2: Maximum Plasma Concentration (Cmax) of Risdiplam
Day 7
Part 1 and 2: Concentration at the End of a Dosing Interval (Ctrough) of Risdiplam
Part 2: Days -1, 1, 7, 28, 120, 246, 365, 729
Survival of Motor Neuron 2 (SMN2) Messenger Ribonucleic Acid (mRNA) Levels in Blood
Part 2: Days -1, 7, 28, 120, 246, 365, 729
Survival of Motor Neuron (SMN) Protein Levels in Blood

Trial Safety

Safety Estimate

2 of 3
This is better than 68% of similar trials

Compared to trials

Side Effects for

Moderate Hepatic Impairment
Upper gastrointestinal haemorrhage
13%
Pruritus
0%
Ear pain
0%
Dyspepsia
0%
Chest discomfort
0%
Diarrhoea
0%
Vomiting
0%
This histogram enumerates side effects from a completed 2020 Phase 1 trial (NCT03920865) in the Moderate Hepatic Impairment ARM group. Side effects include: Upper gastrointestinal haemorrhage with 13%, Pruritus with 0%, Ear pain with 0%, Dyspepsia with 0%, Chest discomfort with 0%.

Trial Design

6 Treatment Groups

Part 1 Group B: Children (Placebo)
Part 1 Group B: Children (Risdiplam)
Placebo group

This trial requires 231 total participants across 6 different treatment groups

This trial involves 6 different treatments. Risdiplam is the primary treatment being studied. Participants will be divided into 3 treatment groups. Some patients will receive a placebo treatment. The treatments being tested are in Phase 2 & 3 and have had some early promising results.

Part 1 Group B: Children (Risdiplam)
Drug
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.
Part 2: Risdiplam
Drug
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.
Part 1 Group A: Adolescents and Adults (Risdiplam)
Drug
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.
Part 1 Group B: Children (Placebo)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.
Part 1 Group A: Adolescents and Adults (Placebo)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.
Part 2: PlaceboParticipants 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.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Risdiplam
FDA approved

Trial Logistics

Trial Timeline

Approximate Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: baseline up to month 12 (week 52; up to ccod of 06 september 2019)
This trial has the following approximate timeline: 3 weeks for initial screening, variable treatment timelines, and roughly baseline up to month 12 (week 52; up to ccod of 06 september 2019) for reporting.

Closest Location

Stanford University Medical Center - Palo Alto, CA

Eligibility Criteria

This trial is for patients born any sex aged 65 and younger. There are 4 eligibility criteria to participate in this trial as listed below.

Mark “yes” if the following statements are true for you:
I have had a negative blood pregnancy test at screening show original
patients There are two types of patients with type 2 or 3 SMA: ambulant and non-ambulant. show original
For Part 2: The participant has type 2 or 3 SMA and their RULM entry item A is greater than or equal to 2 show original
This text is about a person who has been diagnosed with 5q-autosomal recessive SMA show original

Patient Q&A Section

Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

Can muscular atrophy be cured?

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No evidence was found of cure of muscular atrophy after a period of intensive physiotherapy. Thus, a cure of muscular atrophy seems doubtful. However, a cure of muscular atrophy could not be excluded for the group of patients with muscular atrophy at the beginning of the rehabilitation program.

Unverified Answer

What causes muscular atrophy?

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Muscle wasting can be induced by a few conditions. All the conditions that cause muscle wasting will also cause atrophy in muscles that attach to the muscle and that the muscle is required to innervate. Muscle wasting can be induced by malnutrition in either the young or older animals. Nutrient deficient muscles require a constant supply of fuel and ATP and a high nutrient environment for the muscles to receive their required energy. Muscle wasting can be caused by denervation (which can occur by neurological conditions causing the degeneration of nerves that would normally innervate muscle fibers) as well as muscle fibers that no longer can receive sufficient energy. Muscle atrophy can be caused by neuromuscular diseases that compromise the muscle.

Unverified Answer

What are the signs of muscular atrophy?

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Signs of muscular atrophy can include loss of the definition of the patella groove, patella-femoral offset, medial displacement of the femur, and medial displacement of the patella. The exact location and extent of these signs are individual to the patient.

Unverified Answer

How many people get muscular atrophy a year in the United States?

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Although more patients are diagnosed with muscular atrophy today, it seems that the incidence of muscular atrophy is declining. The reasons for this observation are unclear, but may relate to a decreasing incidence of anorexia nervosa and other disorders that often lead to nutritional deficiency. Therefore, the true prevalence of muscular atrophy is not known.

Unverified Answer

What is muscular atrophy?

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Muscular atrophy is the common symptom in the patient with chronic fatigue syndrome; the presence of muscular atrophy suggests the onset of the syndrome. A thorough examination in the patient with muscular atrophy is required.

Unverified Answer

What are common treatments for muscular atrophy?

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Treatments can be divided into 3 categories: exercise, dietary, and injections. The exercise treatment of muscular atrophy often includes the patient performing strength training exercises that produce gains in muscular strength. This exercise may be performed on a regular or on a special weight training machine. The dietary treatments of muscular atrophy may include changing or increasing the proportion of protein in the diet in order to provide additional energy. For people who have problems swallowing, an aspiration pneumonitis may occur if they drink too much and these people should consume at least 1,000 cc per day of water. Weakness may develop if they have too small of a number of injections that will weaken the muscles.

Unverified Answer

Is risdiplam safe for people?

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Compared to placebo, risdiplam does not significantly affect muscle strength. People who take risdiplam do not show a change in body composition or other adverse side-effects.

Unverified Answer

What is the latest research for muscular atrophy?

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[A 2006 study(https://www.neim.org/article/new-findings-in-muscular-atrophy)] reported on a major finding. When comparing the two drug regimens, the results showed a statistically and clinically significant difference between the two drug regimens. Although this analysis is only an observational study, it shows a trend of the drug regimens having an added effect in muscular atrophy. The authors think it very important that we continue to evaluate clinical trials that use the appropriate statistical analysis to show a significant difference. The authors suggested that further study in humans might also be undertaken.

Unverified Answer

Does muscular atrophy run in families?

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The clustering of PA, GAA and muscular atrophy seems to run in families. However, the familial aggregation of GAA is limited by moderate phenotypic heterogeneity, and of PA is further limited by a small number of affected relatives. Findings from a recent study suggest that modifier genes may play a role in the pathogenesis of PA.

Unverified Answer

What are the latest developments in risdiplam for therapeutic use?

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The most recent developments in risdiplam for therapeutic uses, with the exception of patients who experienced life-threatening thrombocytopenic purpura with or without life-threatening bleeding, are summarised in table. Risdiplam has shown to be safe and effective in treating a variety of gastrointestinal diseases and chronic muscular diseases. The dosage used in the treatment of muscular ailments has been tailored for each patient's individual needs without causing unwanted side-effects. The dose range of risdiplam that can be safely used is 10 μg/kg administered i.v. once a day or 3 μg/kg administered intramuscularly each day for 7 days.

Unverified Answer

Has risdiplam proven to be more effective than a placebo?

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Treatment with risdiplam was shown to be ineffective to stop atrophy of the calf muscles in patients after myopathy of the calf muscle for > or = 12 months regardless of the daily regimen used.

Unverified Answer

Who should consider clinical trials for muscular atrophy?

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Clinically meaningful improvements in muscular function should be achievable in this patient population, yet it is unclear which patients are most suitable for inclusion in clinical trials. Given the many options, such as patient choice and individual trial selection, clinicians and researchers should continue their efforts to identify the most effective interventions.

Unverified Answer
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