NCT06377085

Repurposing 5-Azacytidine for the Treatment of Muscle Contractures in Children With Cerebral Palsy

• Status: Enrolling By Invitation
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Sponsor: Shirley Ryan AbilityLab · Academic / Other
• Sex: All
• Age: 2 Years – 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Cerebral palsy (CP) has an enduring impact on the development of the muscles after birth. Research showed that a drug that is currently approved by the FDA to treat myelodysplastic syndromes in adults and children, can be potentially adapted ("repurposed") to support muscle growth. In a controlled dose-escalation study, we will study the preliminary safety, biological properties, and efficacy of this drug, called 5-Azacytidine (AZA). Our hope and overarching expectations are that one day AZA will become a new approved pharmacological treatment to support muscle growth and improve body movement and quality of life in children with CP. Research participants will have five study visits. 1. The first study visit will be a screening within 30 days of the baseline visit and will determine eligibility for the study. The participant will have their blood drawn to check for normal kidney and liver functioning, do a pregnancy test (if applicable), and then the researcher will complete a medical assessment. 2. If the participant is eligible, they will be invited to a second study visit approximately 15 days prior to their scheduled surgery for contracture release. At this visit, the participants will get their blood drawn, do a pregnancy test (if applicable), have a medical assessment performed, and receive their injection. The injection will be a single sub-cutaneous shot in their leg, near the muscle group that will undergo surgical repair. 3. The third visit will be at the participant's scheduled surgery. A small sample of the muscle (i.e., about the size of a pencil eraser) will be surgically removed by the researcher from a muscle group that is already exposed during the procedure. The biopsy will add approximately two to five minutes to the overall procedure time. The participant will also have their blood drawn. 4. The participants will be seen approximately one week after their surgery to complete a medical assessment. 5. The last visit will be about four weeks after the surgery at their post-operative appointment. At this visit, the participant will have their blood drawn and complete a medical assessment to test their range of motion following the surgery. The amount of blood drawn at each time point will be approximately 3 mL, equating to 12 mL of blood total (less than a tablespoon). The purpose of the blood draws is to evaluate safety and biological efficacy of the study drug. The medical assessment will consist of range of motion assessment and wound check performed by the clinicians. These are the same assessments that the clinicians would typically do as part of usual care prior to and after surgery. The purpose of the medical assessment is to evaluate the efficacy of the study drug and ensure the surgical site is healing.

Conditions

• Cerebral Palsy
• Contracture

Interventions

Type	Name	Description
DRUG	Placebo for the AZA 10mg/m^2	Placebo control group for the 10mg/m\^2, one-time subcutaneous injection without the active treatment.
DRUG	Placebo for the AZA 20mg/m^2	Placebo control group for the 20mg/m\^2, one-time subcutaneous injection without the active treatment.
DRUG	Placebo for the AZA 35mg/m^2	Placebo control group for the 35mg/m\^2, one-time subcutaneous injection without the active treatment.
DRUG	Placebo for the AZA 75mg/m^2	Placebo control group for the 75mg/m\^2, one-time subcutaneous injection without the active treatment.
DRUG	5-Azacytidine 10mg/m^2	5-Azacytidine 10mg/m\^2, one-time subcutaneous injection
DRUG	5-Azacytidine 20mg/m^2	5-Azacytidine 20mg/m\^2, one-time subcutaneous injection
DRUG	5-Azacytidine 35mg/m^2	5-Azacytidine 35mg/m\^2, one-time subcutaneous injection
DRUG	5-Azacytidine 75mg/m^2	5-Azacytidine 75mg/m\^2, one-time subcutaneous injection

Timeline

• Start date: 2025-07-01
• Primary completion: 2026-12-01
• Completion: 2027-07-01
• First posted: 2024-04-22
• Last updated: 2025-07-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study