Assessing the Safety, Tolerability, and Efficacy of APR-2020 in Pediatric and Adolescent Subjects With RPS19 Deficient Diamond-Blackfan Anemia

Key Inclusion Criteria

• Confirmed diagnosis of RPS19-deficient DBA.
• Signed informed consent by the subject or legally authorized representative.
• Bone marrow analysis demonstrates normal cytogenetics except for RPS19-deficient DBA.
• Between 2 and 25 years of age, inclusive.
• Eligible for allogeneic marrow or stem cell transplant for DBA (noncritical cardiac and hepatic iron overload).
• Corticosteroid resistance
• Transfusion-dependent anemia
• Willingness to return for long-term follow-up
• Adequate renal and pulmonary function
• Able to undergo hematopoietic stem cell transplant (HSCT) mobilization and apheresis procedures.

Key Exclusion Criteria

• Availability of a suitable, consenting HLA-identical sibling donor.
• Positive viral serology.
• Clinically significant, active bacterial, viral, or fungal infection.
• Any prior or current malignancy, myeloproliferative disorder, or myelodysplastic syndrome, except where therapy was curative excision (ie, in situ squamous cell carcinoma).
• Any concerning cytogenetic abnormalities in hematopoietic cells.
• Previous receipt of an allogeneic transplant or gene therapy.
• Immediate family member with a known or suspected Familial Cancer Syndrome (including, but not limited to breast, colorectal, ovarian, prostate, and pancreatic cancers, excluding DBA).
• Diagnosis of significant psychiatric disorder that could impact the subject's ability to participate in the study, in the opinion of the Investigator.
• History of complex allo-immunization, as determined by the Investigator.
• Female subjects who are lactating/breast feeding or who plan to breastfeed within 6 months following APR-2020 infusion.
• Male and female subjects of childbearing potential who are unwilling to practice highly effective methods of birth control from screening until ≥ 6 months after APR-2020 infusion.
• Female subjects with a positive serum pregnancy test at Screening or who are planning to become pregnant during the study period.
• Liver disease, as evidenced by critical iron overload with magnetic resonance imaging (MRI)
• Heart disease or Type 1 diabetes.
• Evidence of significant pulmonary hypertension, per Investigator assessment.
• Any other condition that would render the subject ineligible for HSCT, as determined by the Investigator.
• Contraindication to stem cell or bone marrow aspiration, mobilization or collection including allergies to filgrastim or plerixafor.
• Currently enrolled in another investigational drug study or received an investigational study drug or procedure within 90 days of study enrollment.
• A physical, functional, or emotional status that would prevent giving informed consent, protocol compliance, or adequate follow-up.
• An assessment by the Investigator that the subject or parents of the subject will not comply with the study procedures outlined in the study protocol.
• Taking prohibited medications.
• Has insufficient personal history of RBC transfusions over the 13 weeks prior to the end of screening.