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

809325

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.

2024-05-01

2026-05-01

2026-05-01

Not yet recruiting

Early phase I

27

Inclusion Criteria: 1. Diagnosis of cerebral palsy. 2. Either achilles or hamstring spasticity with contracture necessitation surgical lengthening. 3. Between 2 and 18 years of age 4. Normal renal and liver function as defined by NCI-CTCAE criteria.71 a. Renal Function (Grade 0 - Normal): i. Creatinine: Within the normal range or ≤ 1.0 times the upper limit of normal (ULN). ii. Glomerular filtration rate (GFR): No significant decrease. b. Liver Function (Grade 0 - Normal): i. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT): Within the normal range or ≤ ULN. ii. Total bilirubin: Within the normal range or ≤ 1.0 times ULN 5. A negative pregnancy test for females of childbearing potential\*. 6. Females of childbearing potential must agree to use contraception consistently from screening to 6 months after their injection. Highly effective methods of contraception are required for females of childbearing potential: 1. Total abstinence from sexual intercourse. 2. Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS). 3. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, which may be oral, intravaginal, or transdermal used in accordance with medical direction. 4. Progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injected, or implanted, and used in accordance with medical direction. 7. Males of childbearing potential\*\* must agree to use contraception consistently from screening until 3 months after the injection. Acceptable methods of contraception for males of childbearing potential are: 1. Total abstinence from sexual intercourse. 2. Condom with spermicide (cream, spray, foam, gel, suppository, or polymer film). * Female of childbearing potential is defined as a female capable of becoming pregnant, which includes patients who have had their first menstrual cycle (menarche). * Male of childbearing potential is defined as a subject who has reached spermarche. Exclusion Criteria: 1. Active infection. 2. Cardiac disease. 3. Allergy to AZA or mannitol. 4. Patient or family who is non-compliant. 5. Received chemotherapy in the preceding three months. 6. Evidence of a hematologic precondition or other malignancy.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'For this Phase 1 trial, we will conduct a dose-escalation study in children having CP who receive 5-Azacytidine (AZA) via a single subcutaneous (SQ) injection two weeks before their surgery, already scheduled to release their contractures. We will use a "3 + 3" dose-escalation design where decisions are based on the rate of toxicity at the current dose level independently from prior dose levels. The primary goal of this study is to determine a Maximum Tolerated Dose (MTD), which will be the highest dose level at which less or equal of 33% of patients experience Dose-Limiting Toxicity (DLT).', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 27, 'type': 'ESTIMATED'}}

2024-04-22