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

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.

Conditions

• Cerebral Palsy
• Contracture

Interventions

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

Sponsors & Collaborators

• Rady Children's Hospital, San Diego

  collaborator OTHER

• Shirley Ryan AbilityLab

  lead OTHER

Principal Investigators

• Andrea Domenighetti, PhD · Shirley Ryan AbilityLab

• Patrick Curran, MD · Rady Children's Hospital, San Diego

• Richard L. Lieber, PhD · Shirley Ryan AbilityLab

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

SEQUENTIAL

Eligibility

Min Age

2 Years

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-07-31

Primary Completion

2026-12-31

Completion

2027-07-31

FDA Drug

Yes

Countries

• United States

Study Locations