5-Azacytidine for Cerebral Palsy

Overseen By Richard L Lieber, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Shirley Ryan AbilityLab

Must not be taking: Chemotherapy

Disqualifiers: Active infection, Cardiac disease, Allergy, others

Compensation: Varies

Number of Visits: 6

Duration: 6-11 weeks

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

In this controlled dose-escalation study, we will study the initial safety, biological properties, and potential efficacy of 5-azacytidine (AZA). Our overarching aspiration is for AZA to evolve into an approved pharmacological treatment, fostering muscle growth and enhancing body movement, ultimately contributing to an improved quality of life in children with CP. The main questions this study aims to answer are: 1. What is the optimal dose of AZA injection that can be used safely in children with CP? 2. Can the optimal safe dose of AZA improve the function of muscle-generating stem cells in children with CP? Each participant will have up to five research visits over the course of the study duration, in which they will participate in: blood draws, pregnancy test(s) (if applicable), medical assessments, and a muscle biopsy during a surgery for muscle contractures. Researchers will compare participants with four different dosages of AZA injections to those with four different dosages of placebo injections. A placebo is a look-alike substance that contains no active drug. They will see if a single injection of AZA at a standard concentration currently approved by the FDA to treat myelodysplastic syndromes, can also safely improve muscle growth and function in children with CP.

Who Is on the Research Team?

Richard L. Lieber, PhD

Principal Investigator

Shirley Ryan AbilityLab

Andrea Domenighetti, PhD

Principal Investigator

Shirley Ryan AbilityLab

Patrick Curran, MD

Principal Investigator

Rady Children's Hospital, San Diego

Are You a Good Fit for This Trial?

Children with cerebral palsy who need surgery for muscle contractures can join this trial. They must have normal kidney and liver function, not be pregnant, and either abstain from sex or use certain birth control methods.

Inclusion Criteria

My kidney function is normal, based on my creatinine levels.

I need surgery to lengthen my Achilles or hamstring due to stiffness.

My kidney and liver functions are normal.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive a single subcutaneous injection of AZA or placebo and undergo surgery for muscle contracture release

6-11 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including range of motion assessments and wound checks

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• 5-Azacytidine

Trial Overview The study tests different doses of a drug called 5-Azacytidine (AZA) to find the safest amount that might help muscles grow better in kids with CP. It compares these doses against placebos during up to five visits involving blood tests, medical exams, and a muscle biopsy.

How Is the Trial Designed?

Group I: AZA 75mg/m^2 Experimental Treatment 1 Intervention

5-Azacytidine, subcutaneous injection, 75mg/m\^2, one subcutaneous injection for duration of study (estimated at 46 - 76 days)

Group II: AZA 35mg/m^2 Experimental Treatment 1 Intervention

5-Azacytidine, subcutaneous injection, 35mg/m\^2, one subcutaneous injection for duration of study (estimated at 46 - 76 days)

Group III: AZA 20mg/m^2 Experimental Treatment 1 Intervention

5-Azacytidine, subcutaneous injection, 20mg/m\^2, one subcutaneous injection for duration of study (estimated at 46 - 76 days)

Group IV: AZA 10mg/m^2 Experimental Treatment 1 Intervention

5-Azacytidine, subcutaneous injection, 10mg/m\^2, one subcutaneous injection for duration of study (estimated at 46 - 76 days)

Group V: Placebo for 35mg/m^2 Placebo Group 1 Intervention

Placebo, subcutaneous injection, 35mg/m\^2, one subcutaneous injection without the active treatment for duration of study (estimated at 46 - 76 days)

Group VI: Placebo for 20mg/m^2 Placebo Group 1 Intervention

Placebo, subcutaneous injection, 20mg/m\^2, one subcutaneous injection without the active treatment for duration of study (estimated at 46 - 76 days)

Group VII: Placebo for 10mg/m^2 Placebo Group 1 Intervention

Placebo, subcutaneous injection, 10mg/m\^2, one subcutaneous injection without the active treatment for duration of study (estimated at 46 - 76 days)

Group VIII: Placebo for 75mg/m^2 Placebo Group 1 Intervention

Placebo, subcutaneous injection, 75mg/m\^2, one subcutaneous injection without the active treatment for duration of study (estimated at 46 - 76 days)

Who Is Running the Clinical Trial?

Shirley Ryan AbilityLab

Lead Sponsor

Trials

212

Recruited

17,900+

Rady Children's Hospital, San Diego

Collaborator

Trials

42

Recruited

14,300+