safety & efficacy of allorx sc® in pths patients

Conditions: Pitt Hopkins Syndrome

Summary: this study will evaluate the safety of allorx stem cells® in subjects with pitt hopkins syndrome ages 2-45 with a molecularly confirmed pathogenic mutation in tcf4 or 18q deletion including tcf4. participants will receive mesenchymal stem cells infusions every 3 months for a year with completion of outcome measures to assess the efficacy of the product.

this is a phase 1/2, randomized placebo controlled double blinded standard dose study to evaluate the safety and tolerability of allorx® stem cells in pediatric patients with a confirmed diagnosis of a tcf4 mutation consistent with haploinsufficiency causing pths. approximately 26 patients (male and female) ages ≥ 2 and≤ 45 years of age with a genetically confirmed diagnosis of pitt-hopkins syndrome caused by molecular findings consistent with a pathogenic mutation in the gene tcf4. written informed consent will be obtained from the patient's parent or legal guardian/ authorized representative (lar) prior to participation in the study. the study includes screening, baseline, treatment and safety follow up periods. the procedure for intravenous administration is performed under the supervision of clinician with experience caring for patients with pths. each patient will remain inpatient for at least 24 hours after the initial dose of allorx, for frequent vital sign monitoring, electrocardiogram (ecg), blood and urine safety tests, and neurologic assessments. investigators will work closely with the parent/legal guardian to ensure that any signs of discomfort/distress are immediately communicated to study staff. for the administration of the initial dose of study drug in each study cohort, patients will be dosed in a sequential fashion with no more than one patient receiving their first dose of study drug on the same day. an independent data dsmb will review all safety and laboratory data throughout the study on a periodic basis and ad hoc should an sae occur. the dsmb will also review all available safety data when all patients have received 2 doses of allorx and have had at least two weeks of follow-up in order to determine if it is safe to dose the next patient.

Eligibility criteria:
inclusion criteria: * signed informed consent from parent(s) or legal guardian(s)/authorized representative(s) (lar) * documented genetic confirmation of mutation in tcf4, with clinical diagnosis of pitt hopkins syndrome (pths) * stable seizure control (defined as clinically stable with no changes in antiepileptic medications or use of rescue medication over the prior 1 month before the screening visit, other than weight associated dose adjustments) * normal renal function with serum creatinine and spot urine protein within normal limits * willing and able to comply with scheduled visits, drug administration plan, laboratory tests, study restrictions, and all study procedures, including intravenous infusion exclusion criteria: * any change in medications or diet/supplements intended to treat symptoms of pths (e.g., sleeping aids, supplements, cannabidiol products) over the prior 3 months before screening * inability to ambulate independently or with an assistive device or caregiver handhold * any bleeding or platelet disorder * any clinically significant (cs) cardiovascular, endocrine, hepatic, renal, pulmonary, gastrointestinal, neurologic, malignant, metabolic, psychiatric, or other condition that, in the judgment of the investigator, will pose a safety risk, make the patient unsuitable for participation in, and/or unable to complete the study procedures * any laboratory abnormality, that, in the investigator's opinion, could adversely affect the safety of the patient, make it unlikely that the course of treatment or follow up would be completed, or impair the assessment of study result * known positive for hepatitis b virus, hepatitis c virus, or human immunodeficiency virus (hiv). patient is pregnant or lactating * usage of drugs that increase the risk of bleeding (e.g., heparin, low molecular weight heparin, platelet inhibitors). * use of any investigational oligonucleotide and any investigational drugs in the past 6 months * any prior use of gene therapy