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

Summary

Brief summary The goal of this clinical trial is to learn if APR-2020 is safe and can help treat Diamond-Blackfan Anemia (DBA) in adolescents and children. The main questions it aims to answer are: * Is APR-2020 safe and well tolerated? * Does APR-2020 modify or correct an underlying genetic condition which causes DBA? * Does APR-2020 reduce or eliminate the need for blood transfusions and/or restore certain blood counts affected by DBA? Participants will: * Take the drug one time as an infusion. * Undergo two rounds of a cellular harvest procedure in which their own cells will be used in the manufacturing of their own participant-specific product. * Initially return to the clinic for two years of follow up at increasingly sparse intervals.

Timeline

Start

2026-04-16

Primary completion

2027-04

Completion

2028-09

Publications

• Background Da Costa L, Leblanc T, Mohandas N. Diamond-Blackfan anemia. Blood. 2020 Sep 10;136(11):1262-1273. doi: 10.1182/blood.2019000947.
• Background Dahl M, Warsi S, Liu Y, Debnath S, Billing M, Siva K, Flygare J, Karlsson S. Bone marrow transplantation without myeloablative conditioning in a mouse model for Diamond-Blackfan anemia corrects the disease phenotype. Exp Hematol. 2021 Jul;99:44-53.e2. doi: 10.1016/j.exphem.2021.06.002. Epub 2021 Jun 12.
• Background Garelli E, Quarello P, Giorgio E, Carando A, Menegatti E, Mancini C, Di Gregorio E, Crescenzio N, Palumbo O, Carella M, Dimartino P, Pippucci T, Dianzani I, Ramenghi U, Brusco A. Spontaneous remission in a Diamond-Blackfan anaemia patient due to a revertant uniparental disomy ablating a de novo RPS19 mutation. Br J Haematol. 2019 Jun;185(5):994-998. doi: 10.1111/bjh.15688. Epub 2018 Nov 20. No abstract available.
• Background Flygare J, Rayon Estrada V, Shin C, Gupta S, Lodish HF. HIF1alpha synergizes with glucocorticoids to promote BFU-E progenitor self-renewal. Blood. 2011 Mar 24;117(12):3435-44. doi: 10.1182/blood-2010-07-295550. Epub 2010 Dec 21.
• Background Freiman S, Chen J, Baudet A et al. Ex Vivo APR 2020 Molecular Efficacy Report. 2025. Lund University.
• Background Jillella AP, Ustun C. What is the optimum number of CD34+ peripheral blood stem cells for an autologous transplant? Stem Cells Dev. 2004 Dec;13(6):598-606. doi: 10.1089/scd.2004.13.598.
• Background Liu Y, Dahl M, Debnath S, Rothe M, Smith EM, Grahn THM, Warsi S, Chen J, Flygare J, Schambach A, Karlsson S. Successful gene therapy of Diamond-Blackfan anemia in a mouse model and human CD34+ cord blood hematopoietic stem cells using a clinically applicable lentiviral vector. Haematologica. 2022 Feb 1;107(2):446-456. doi: 10.3324/haematol.2020.269142.
• Background Moreno-Carranza B, Gentsch M, Stein S, Schambach A, Santilli G, Rudolf E, Ryser MF, Haria S, Thrasher AJ, Baum C, Brenner S, Grez M. Transgene optimization significantly improves SIN vector titers, gp91phox expression and reconstitution of superoxide production in X-CGD cells. Gene Ther. 2009 Jan;16(1):111-8. doi: 10.1038/gt.2008.143. Epub 2008 Sep 11.
• Background Peslak SA, Wenger J, Bemis JC, Kingsley PD, Koniski AD, McGrath KE, Palis J. EPO-mediated expansion of late-stage erythroid progenitors in the bone marrow initiates recovery from sublethal radiation stress. Blood. 2012 Sep 20;120(12):2501-11. doi: 10.1182/blood-2011-11-394304. Epub 2012 Aug 13.
• Background Sieff C. DBA Syndrome.GeneReviews. Accessed April 2025. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK7047/#:~:text=Diamond%2DBlackfan%20anemia%20(DBA),in%
• Background Swartzrock L, Liu YL, Hoang H, et al. Disease correction of a diamond blackfan anemia mouse model using non genotoxic conditioning and hematopoietic stem cell transplantation. Blood 2024;144(Suppl 1):194 5.
• Background Yoshida M, Bhoopala, S, Toki T, et al. Polyclonal somatic gene rescue via uniparental disomy confers multilineage hematopoietic potential in treatment-independent patients with DBA syndrome. Blood 2025;146(1):746.
• Background Venugopal P, Moore S, Lawrence DM, George AJ, Hannan RD, Bray SC, To LB, D'Andrea RJ, Feng J, Tirimacco A, Yeoman AL, Young CC, Fine M, Schreiber AW, Hahn CN, Barnett C, Saxon B, Scott HS. Self-reverting mutations partially correct the blood phenotype in a Diamond Blackfan anemia patient. Haematologica. 2017 Dec;102(12):e506-e509. doi: 10.3324/haematol.2017.166678. Epub 2017 Sep 29. No abstract available.
• Background Vlachos A, Osorio DS, Atsidaftos E, Kang J, Lababidi ML, Seiden HS, Gruber D, Glader BE, Onel K, Farrar JE, Bodine DM, Aspesi A, Dianzani I, Ramenghi U, Ellis SR, Lipton JM. Increased Prevalence of Congenital Heart Disease in Children With Diamond Blackfan Anemia Suggests Unrecognized Diamond Blackfan Anemia as a Cause of Congenital Heart Disease in the General Population: A Report of the Diamond Blackfan Anemia Registry. Circ Genom Precis Med. 2018 May;11(5):e002044. doi: 10.1161/CIRCGENETICS.117.002044. No abstract available.
• Background Wlodarski MW, Vlachos A, Farrar JE, Da Costa LM, Kattamis A, Dianzani I, Belendez C, Unal S, Tamary H, Pasauliene R, Pospisilova D, de la Fuente J, Iskander D, Wolfe L, Liu JM, Shimamura A, Albrecht K, Lausen B, Bechensteen AG, Tedgard U, Puzik A, Quarello P, Ramenghi U, Bartels M, Hengartner H, Farah RA, Al Saleh M, Hamidieh AA, Yang W, Ito E, Kook H, Ovsyannikova G, Kager L, Gleizes PE, Dalle JH, Strahm B, Niemeyer CM, Lipton JM, Leblanc TM; international Diamond-Blackfan anaemia syndrome guideline panel. Diagnosis, treatment, and surveillance of Diamond-Blackfan anaemia syndrome: international consensus statement. Lancet Haematol. 2024 May;11(5):e368-e382. doi: 10.1016/S2352-3026(24)00063-2.

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