APR-2020 for children and adolescents with RPS19-deficient Diamond-Blackfan anemia

A Phase 1, Open-label, Single-arm Study of APR 2020 in Transfusion Dependent, Steroid Resistant Pediatric and Adolescent Subjects With RPS19 Deficient Diamond Blackfan Anemia by Transplantation of Autologous CD34+ Stem Cells Transduced With CLIN LV EFS coRPS19 PRE* (APR-2020)

This study will test whether a one-time infusion of APR-2020, manufactured from each patient’s own cells, is safe and can reduce or eliminate the need for blood transfusions in children and teens with RPS19-deficient Diamond-Blackfan anemia.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 4 (estimated)
• Ages: 2 Years to 18 Years
• Sex: All
• Sponsor: Apriligen, Inc. (Industry-sponsored)
• Locations: 2 sites (Stanford, California and 1 other locations)
• Trial ID: NCT07476183 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm Phase 1 study tests the safety, tolerability, and preliminary efficacy of a single infusion of APR-2020 in transfusion-dependent, steroid-resistant pediatric and adolescent patients with RPS19-deficient Diamond-Blackfan anemia. Each participant undergoes two rounds of cellular harvest for manufacture of an autologous product, followed by a one-time infusion and close monitoring. The protocol includes frequent clinic visits initially and scheduled follow-up over two years to track adverse events, changes in blood counts, and transfusion requirements. The primary focus is safety and tolerability, with secondary measures of hematologic response and reduction in transfusion dependence.

Who should consider this trial

Good fit: Children and adolescents aged 2 to 18 with a confirmed diagnosis of RPS19-deficient DBA who are transfusion-dependent, corticosteroid-resistant, and able to undergo HSCT mobilization and apheresis are the intended participants.

Not a fit: Patients with non-RPS19 DBA genotypes, an available HLA-identical sibling donor, active serious infections, positive viral serology, or a history of malignancy are unlikely to be eligible or to benefit from this protocol.

Why it matters

Potential benefit: If successful, APR-2020 could correct the underlying RPS19 defect in treated patients and substantially reduce or eliminate their need for ongoing blood transfusions.

How similar studies have performed: This autologous, gene-modifying cell therapy approach is relatively novel for RPS19-deficient DBA with limited direct clinical precedent, though similar autologous gene-modified cell therapies have shown promise in other inherited bone marrow failure disorders.

Eligibility criteria

Key Inclusion Criteria:

1. Confirmed diagnosis of RPS19-deficient DBA.
2. Signed informed consent by the subject or legally authorized representative.
3. Bone marrow analysis demonstrating normal cytogenetics except for RPS19-deficient DBA.
4. Subjects are between 2 and 18 years of age, inclusive.
5. Eligible for allogeneic marrow or stem cell transplant for DBA (non-critical cardiac and hepatic iron overload).
6. Corticosteroid resistance
7. Transfusion-dependent anemia
8. Willingness to return for long-term follow-up
9. Adequate renal and pulmonary function
10. Able to undergo hematopoietic stem cell transplant (HSCT) mobilization and apheresis procedures.

Key Exclusion Criteria:

1. Availability of a suitable, consenting HLA-identical sibling donor.
2. Positive viral serology.
3. Clinically significant, active bacterial, viral, or fungal infection.
4. Any prior or current malignancy, myeloproliferative disorder, or myelodysplastic syndrome, except where therapy was curative excision (ie, in situ squamous cell carcinoma).
5. Any concerning molecular or cytogenetic abnormalities in hematopoietic cells.
6. Previous receipt of an allogeneic transplant or gene therapy.
7. 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).
8. Diagnosis of significant psychiatric disorder that could impact the subject's ability to participate in the study, in the opinion of the Investigator.
9. History of complex allo-immunization, as determined by the Investigator.
10. Women who are lactating/breast feeding or who plan to breastfeed within 6 months following APR-2020 infusion.
11. Men and females of childbearing potential who are unwilling to practice highly effective methods of birth control through the duration of the study.
12. Females with a positive serum pregnancy test at Screening or who are planning to become pregnant during the study period.
13. Liver disease, as evidenced by critical iron overload with magnetic resonance imaging (MRI)
14. Heart disease or Type 1 diabetes.
15. Evidence of significant pulmonary hypertension, per Investigator assessment.
16. Any other condition that would render the subject ineligible for HSCT, as determined by Investigator.
17. Contraindication to stem cell or bone marrow aspiration, mobilization or collection including allergies to filgrastim or plerixafor.
18. Currently enrolled in another investigational drug study or received an investigational study drug or procedure within 90 days of study enrollment.
19. A physical or emotional status that would prevent giving informed consent, protocol compliance, or adequate follow-up.
20. 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.
21. Taking prohibited medications.

Where this trial is running

Stanford, California and 1 other locations

• Stanford University - Stanford Children's Health — Stanford, California, United States (Not_yet_recruiting)
• Boston Children's Hospital — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Study coordinator: Nova Silver

Conditions RPS19 Deficient Diamond-Blackfan Anemia; RPS19; Diamond-Blackfan Anemia; DBA