Study to Evaluate of EXG34217 in Patients With Telomere Biology Disorders With Bone Marrow Failure

Study Overview
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Brief Summary
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This is a Phase I/II, open label, single center study to assess the safety and tolerability of EXG34217 in bone marrow failure patients with telomere biology disorders.

Detailed Description
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This is a Phase I/II, open label study in up to 12 subjects with telomere biology disorders with bone marrow failure. The study is open to all participants regardless of gender or ethnicity. Subjects who are enrolled but not evaluable will be replaced. Subjects will sign a consent form prior to any study related procedure and will complete baseline screening assessments. Subjects for this study will not require any preparative regimen such as chemotherapy or radiation. The study will be conducted in three parts Peripheral blood mononuclear cells (PBMNCs) collection; mobilization and apheresis, Ex vivo cell processing Processed cell infusion and post-infusion safety monitoring, Follow-up (Week 2, 3,4,5, Months 1, 2,3,4,5,6,9 and 12)

Official Title
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A Phase I/II Study to Evaluate the Safety and Tolerability of EXG34217 in Patients With Telomere Biology Disorders With Bone Marrow Failure

Conditions
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Telomere Shortening, Bone Marrow Failure

Intervention / Treatment
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* Biological: EXG34217


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years. Mild or moderate bone marrow failure defined by satisfying specific conditions. Diagnosis of telomere biology disorders Exclusion Criteria: Women of child bearing potential or breastfeeding. Patients with cancer who are on active chemotherapeutic treatment. Patients with severe bone marrow failure. Clonal cytogenetic abnormalities associated with MDS or AML on bone marrow examination. Uncontrolled bacterial, viral or fungal infections. Prior allogeneic marrow or stem cell transplantation. Patients who are not eligible for G-CSF and plerixafor dosing. Patients who are not eligible for the apheresis. Patients currently taking or have taken danazol and androgens within 60 days prior to Day 1. Patients with any other clinically relevant acute or chronic diseases which could interfere with the patients' safety during the trial, expose them to undue risk, or which could interfere with study objectives. Patients who have participated in another clinical trial with an investigational drug within the previous 30 days.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EXG34217<br>single autologous CD34+ cells contacted ex vivo with EXG-001 | Biological: EXG34217<br>* Single infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events -Safety by Incidence of Treatment-Emergent Adverse Events | Number of participants with treatment-related adverse events as assessed by CTCAE v4.03. Incidence and nature of adverse events, vital signs, weight. | Multiple times for the duration of the study (baseline through Month 12) | 
| Number of participants with a change in in physical examination | Physical examination changes General appearance ,Head, eyes, ears, nose, and throat, Respiratory, Cardiovascular, Musculoskeletal, Abdomen, Neurologic, Extremities, Dermatologic, Lymphatic) | Multiple times for the duration of the study (baseline through Month 12) | 
| Number of participants with a change in Electrocardiography (ECG) | ECG (standard digital 12-lead in singlicate) | Multiple times for the duration of the study (baseline through Month 12) | 
| Number of participants with a change in clinical laboratory evaluations | Changes in clinical laboratory evaluations (Hematology, Blood chemistry, Coagulation, and Urinalysis) | Multiple times for the duration of the study (baseline through Month 12) | 
| Number of participants with a change of Immunogenicity | Change in Antibody against virus vector and transgene | Multiple times for the duration of the study (baseline through Month 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with a change in telomere length | Change in telomere length in any peripheral blood cells | Screening, Month1,3,6 and 12 | 
| Number of participants with improvement of blood counts. | Blood counts: neutrophils,platelets, or hemoglobin | Multiple times for the duration of the study (baseline through Month 12) |