Pitt Hopkins Syndrome
Conditions
Brief 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.
Detailed description
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.
Interventions
BIOLOGICALAlloRx Stem Cells®
Umbilical cord-derived allogeneic mesenchymal stem cells
OTHERPlacebo control
Placebo infusion without mesenchymal stem cells
Sponsors
Vitro Biopharma Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized Placebo Controlled Double Blinded
Eligibility
Sex/Gender
ALL
Age
2 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Incidence of adverse events improvement) in one or more areas of ailments related to PTHS | Change from baseline to day 456 (end of study) | Collection of all adverse events (AEs) |
| Safety: Incidence of serious adverse events | Change from baseline to day 456 (end of study) | Collection of all serious adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in adaptive function | Change from baseline to day 456 (end of study) | Vineland Adaptive Behavioral Scale-3 |
| Change in motor function in individuals with PTHS | Change from baseline to day 456 (end of study) | Ambulation measures by video and wearable device |
| Change in communication abilities in individuals with PTHS. | Change from baseline to day 456 (end of study) | Observer-Reported Communication Ability Measure (ORCA) |
| Change in sleep habits | Change from baseline to day 456 (end of study) | Sleep diary |
| Change in autistic features | Change from baseline to day 456 (end of study) | Childhood Autism Rating Scale (CARS) |
| Change in breath holding spells | Change from baseline to day 456 (end of study) | Diary of breath holding spells |
| Change in cognition | Change from baseline to day 456 (end of study) | Bayley Scales of Infant Development (BSID-4) |
| Change in global clinical status | Change from baseline to day 456 (end of study) | PTHS-specific Clinical Global Impression Scale |
| Change in gastrointestinal health | Change from baseline to day 456 (end of study) | Gastrointestinal Health Questionnaire |
| Change in parent assessment of quality of life | Change from baseline to day 456 (end of study) | Pediatric Quality of Life Questionnaire |
Outcome results
None listed