Cell Therapy for Duchenne Muscular Dystrophy

(HOPE-3 Trial)

Recruiting at 19 trial locations

Overseen By Han Phan, MD

Age: Any Age

Sex: Male

Trial Phase: Phase 3

Sponsor: Capricor Inc.

Must be taking: Glucocorticoids

Must not be taking: Metformin, Insulin, Exon skipping

Disqualifiers: Low LVEF, High BMI, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 14

Duration: 12 months

104 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a cell therapy called CAP-1002 in boys and young men with Duchenne muscular dystrophy. The therapy involves giving special cells through an IV to help improve muscle function. The goal is to see if this treatment can repair or regenerate damaged muscles.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you must have been on a stable dose of systemic glucocorticoids for at least 6 months before the study. Some medications, like metformin, insulin, and certain exon skipping therapies, should not have been started recently. It's best to discuss your specific medications with the trial team.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you have been on a stable dose of systemic glucocorticoids for at least 6 months before joining. If you are taking certain medications like metformin, insulin, or human growth hormone, you may need to have been on a stable dose for a specific period before participating.

What data supports the idea that Cell Therapy for Duchenne Muscular Dystrophy (also known as: CAP-1002, Deramiocel, Placebo, Control, Dummy Treatment) is an effective treatment?

The available research shows that the cell therapy, specifically DT-DEC01, has shown promising results in treating Duchenne Muscular Dystrophy (DMD). In studies involving DMD patients, improvements were observed in walking ability, muscle strength, and daily activities. For example, patients showed better performance in walking tests and increased muscle strength. Additionally, the therapy improved heart and lung function, which are critical for DMD patients. Importantly, these benefits were achieved without serious side effects, making DT-DEC01 a safe and potentially effective treatment option for DMD. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment CAP-1002 for Duchenne Muscular Dystrophy?

The research on DT-DEC01, a similar cell therapy, shows promising results for Duchenne Muscular Dystrophy, with improvements in muscle function and strength, as well as cardiac and respiratory health, without serious side effects. This suggests that cell-based therapies like CAP-1002 could potentially be effective for treating DMD. ^{1 2 3 4 5}

What safety data is available for cell therapy in Duchenne Muscular Dystrophy?

The safety of DT-DEC01, a Dystrophin Expressing Chimeric cell therapy, has been confirmed in multiple studies. No adverse events or serious adverse events were observed up to 22 months after administration. The therapy does not require immunosuppression and carries no risk of off-target mutations. Preclinical studies in animal models also confirmed the long-term safety and lack of tumorigenicity of DEC therapy. Overall, these studies establish the safety of DEC cell therapy for Duchenne Muscular Dystrophy patients. ^{1 2 3 4 6}

Is the cell therapy for Duchenne Muscular Dystrophy safe for humans?

The cell therapy, known as DT-DEC01 or DEC, has been shown to be safe in humans with Duchenne Muscular Dystrophy, as no adverse events or serious adverse events were reported up to 22 months after administration. Additionally, preclinical studies in animal models confirmed the long-term safety of the therapy, with no evidence of DNA damage or tumor formation. ^{1 2 3 4 6}

Is the treatment CAP-1002, Placebo a promising treatment for Duchenne Muscular Dystrophy?

The information provided does not mention CAP-1002 or Placebo as a promising treatment for Duchenne Muscular Dystrophy. Instead, it highlights DT-DEC01, a cell therapy, as a promising treatment due to its safety and positive effects on muscle strength and function in patients. ^{1 2 3 4 7}

How is the CAP-1002 treatment for Duchenne Muscular Dystrophy different from other treatments?

CAP-1002 is a unique cell therapy that involves the use of Deramiocel, which is a novel approach compared to traditional treatments that mainly focus on managing symptoms. Unlike other therapies, CAP-1002 does not require immunosuppression and can be readministered, offering a potentially universal treatment option for all patients with Duchenne Muscular Dystrophy. ^{1 2 3 4 7}

Research Team

Craig McDonald

Principal Investigator

University of California, Davis

Mark Awadalla

Principal Investigator

Capricor Inc.

Eligibility Criteria

This trial is for boys and young men at least 10 years old with genetically confirmed Duchenne muscular dystrophy (DMD). They must have been on stable glucocorticoids for a year, have up-to-date immunizations, and adequate venous access. Ambulatory participants should take more than 10 seconds to walk/run 10 meters; non-ambulatory ones should have lost independent walking between ages 10-18.

Inclusion Criteria

I have good veins for IV treatments and blood tests.

I am using effective birth control methods if I'm sexually active.

I lost the ability to walk on my own between ages 10 and 18.

Exclusion Criteria

Inability to perform consistent PUL 2.0 measurement within specific ranges during paired testing at screening.

Treatment with an investigational product within 6 months prior to randomization.

I cannot fully straighten my arms due to stiffness.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either deramiocel or placebo every 3 months for a total of 4 doses during the first 12 months

12 months

Visits at Baseline/Day 1, Month 1, and Months 3, 6, 9, and 12

Open-label extension

All participants receive 4 doses of deramiocel for an additional 12 months

12 months

Visits at Month 12, 15, 18, and 21

Long-term open-label extension

Participants continue to receive deramiocel every 3 months until commercial availability or trial termination

Indefinite

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CAP-1002
• Placebo

Trial Overview The HOPE-3 trial tests CAP-1002 cell therapy's effectiveness in improving muscle function in DMD patients. Participants are randomly assigned to receive either CAP-1002 or placebo every three months over a year, followed by an open-label extension where all get CAP-1002.

Participant Groups

Group I: Deramiocel (CAP-1002) Experimental Treatment 1 Intervention

Cohort A: Approximatetly 29 subjects will receive deramiocel (CAP-1002A) active treatment consisting of 150 million cardiosphere-derived cells (CDCs) via intravenous infusion every 3 months Cohort B: Approximately 22 participants will receive deramiocel (CAP-1002B) active treatment consisting of 150 million cardiosphere-derived cells (CDCs) via intravenous infusion every 3 months

Group II: Placebo Placebo Group 1 Intervention

Cohort A: Approximately 29 subjects will receive a Placebo solution via intravenous infusion every 3 months Cohort B: Approximately 22 participants will receive a Placebo solution via intravenous infusion every 3 months

Who Is Running the Clinical Trial?

Capricor Inc.

Lead Sponsor

Trials

12

Recruited

480+

Findings from Research

The DT-DEC01 cell therapy demonstrated a strong safety profile with no adverse events reported up to 21 months after administration, indicating it is a safe treatment option for patients with Duchenne Muscular Dystrophy (DMD).

Functional improvements were observed in patients, including better performance in the 6-Minute Walk Test and other assessments, suggesting that DT-DEC01 may effectively enhance muscle function and overall health in DMD patients over a 12-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of DT-DEC01 Therapy in Duchenne Muscular Dystrophy Patients: A 12 - Month Follow-Up Study After Systemic Intraosseous Administration. Siemionow, M., Biegański, G., Niezgoda, A., et al.[2023]

The first-in-human study of DEC cell therapy for Duchenne Muscular Dystrophy (DMD) showed no adverse events in the first 3 patients over 14 months, indicating a strong safety profile for this novel treatment.

Patients receiving DEC therapy demonstrated significant improvements in muscle function and strength, as measured by various functional tests, suggesting that this therapy could effectively enhance quality of life for DMD patients without the need for immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dystrophin Expressing Chimeric (DEC) Cell Therapy for Duchenne Muscular Dystrophy: A First-in-Human Study with Minimum 6 Months Follow-up. Heydemann, A., Bieganski, G., Wachowiak, J., et al.[2023]

A new immunodeficient rat model of Duchenne muscular dystrophy (DMD) was developed, showing similar disease characteristics to human patients, which is crucial for studying potential treatments.

Successful engraftment of human myoblasts in this rat model indicates its potential for preclinical studies on cell transplantation therapies for DMD, paving the way for future research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new immunodeficient Duchenne muscular dystrophy rat model to evaluate engraftment after human cell transplantation. Sato, M., Goto, M., Yamanouchi, K., et al.[2023]

The novel DT-DEC01 therapy, which uses Dystrophin Expressing Chimeric (DEC) cells, was found to be safe in a small study of 3 boys aged 6-15 years, with no therapy-related adverse events reported up to 22 months after treatment.

Preliminary efficacy was observed through electromyography (EMG) assessments, showing increased motor unit potentials in treated muscles at 12 months, indicating potential benefits for muscle function in boys with Duchenne muscular dystrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Motor Unit Potentials Duration as the Biomarker of DT-DEC01 Cell Therapy Efficacy in Duchenne Muscular Dystrophy Patients up to 12 Months After Systemic-Intraosseous Administration. Niezgoda, A., Biegański, G., Wachowiak, J., et al.[2023]

Transplantation of dystrophin-expressing chimeric (DEC) cells derived from myoblasts significantly increased dystrophin expression in the skeletal, cardiac, and respiratory muscles of a mouse model for Duchenne muscular dystrophy (DMD), leading to improved muscle function and reduced pathology.

The study demonstrated that DEC transplantation not only preserved heart function and respiratory capacity but also improved muscle strength and reduced inflammation and fibrosis, suggesting a promising new therapeutic approach for enhancing the overall health of DMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human dystrophin expressing chimeric (DEC) cell therapy ameliorates cardiac, respiratory, and skeletal muscle's function in Duchenne muscular dystrophy. Siemionow, M., Langa, P., Harasymczuk, M., et al.[2022]

The study demonstrated that human dystrophin expressing chimeric (DEC) cell therapy is safe for long-term use, showing no complications or DNA damage in a mouse model of Duchenne muscular dystrophy (DMD) after 180 days post-administration.

Biodistribution analysis confirmed that DEC cells effectively targeted the heart, diaphragm, and gastrocnemius muscle while showing minimal presence in non-target organs, indicating a promising therapeutic approach for DMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Biodistribution and Safety of Human Dystrophin Expressing Chimeric Cell Therapy After Systemic-Intraosseous Administration to Duchenne Muscular Dystrophy Model. Siemionow, M., Brodowska, S., Langa, P., et al.[2022]

In a 7-month phase I clinical trial involving eight boys with Duchenne muscular dystrophy, the autologous transplantation of muscle-derived CD133+ stem cells was found to be safe, with no local or systemic side effects reported.

The treatment led to positive changes in muscle structure, including an increased ratio of capillaries to muscle fibers and a shift towards faster myosin-positive muscle fibers, suggesting potential benefits for muscle repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous transplantation of muscle-derived CD133+ stem cells in Duchenne muscle patients. Torrente, Y., Belicchi, M., Marchesi, C., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of DT-DEC01 Therapy in Duchenne Muscular Dystrophy Patients: A 12 - Month Follow-Up Study After Systemic Intraosseous Administration. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Dystrophin Expressing Chimeric (DEC) Cell Therapy for Duchenne Muscular Dystrophy: A First-in-Human Study with Minimum 6 Months Follow-up. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A new immunodeficient Duchenne muscular dystrophy rat model to evaluate engraftment after human cell transplantation. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Assessment of Motor Unit Potentials Duration as the Biomarker of DT-DEC01 Cell Therapy Efficacy in Duchenne Muscular Dystrophy Patients up to 12 Months After Systemic-Intraosseous Administration. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Human dystrophin expressing chimeric (DEC) cell therapy ameliorates cardiac, respiratory, and skeletal muscle's function in Duchenne muscular dystrophy. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Long-Term Biodistribution and Safety of Human Dystrophin Expressing Chimeric Cell Therapy After Systemic-Intraosseous Administration to Duchenne Muscular Dystrophy Model. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Autologous transplantation of muscle-derived CD133+ stem cells in Duchenne muscle patients. [2019]