Gene therapy clinical trials for TDT and SCD patients
| Trial number . | Phase . | Sponsor . | Site . | Start date/ recruitment status . | Number of patients . | Vector and transgene (nuclease and DP name) . | Cell source . | Conditioning . | DP administration . | Last update (www.clinicaltrials.gov) . | References . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| β-Thalassemia | |||||||||||
| LG001 | 1/2 | bluebird bio | France | September 2006/completed | 2* | HPV569 (βA-T87Q-globin) | G-CSF mPBCs or BM | Myeloablative (busulfan) | IV | NA | 26 |
| NCT01639690 | 1 | Memorial Sloan Kettering Cancer Center | United States | July 2012/active, not recruiting | 4 | TNS9.3.55 (βA-globin) | G-CSF mPBCs | Nonmyeloablative (busulfan 8 mg/kg) | IV | 6 June 2018 | 113 |
| NCT02151526 (HGB205) | 1/2 | bluebird bio | France | July 2013/active, not recruiting | 4 | BB305 (βA-T87Q-globin) | G-CSF + plerixafor mPBCs | Myeloablative (busulfan) | IV | 31 January 2019 | 28 |
| NCT01745120 (HGB204) | 1/2 | bluebird bio | United States, Australia, Thailand | August 2013/completed | 18 | BB305 (βA-T87Q-globin) | G-CSF + plerixafor mPBCs | Myeloablative (busulfan) | IV | 8 May 2019 | 28 |
| NCT02453477 | 1/2 | IRCCS San Raffaele | Italy | May 2015/active, not recruiting | 10 | GLOBE (βA-globin) | G-CSF + plerixafor mPBCs | Myeloablative (thiotepa + threosulfan) | IO | 4 May 2018 | 33 |
| NCT02906202 (HGB207) | 3 | bluebird bio | United States, France, Germany, Greece, Italy, Thailand, United Kingdom, | July 2016/recruiting | 23 (estimated) | BB305 (βA-T87Q-globin) | G-CSF + plerixafor mPBCs | Myeloablative (busulfan) | IV | 31 January 2019 | 31 |
| NCT02906202 (HGB212) | 3 | bluebird bio | United States, France, Germany, Greece, Italy, Thailand, United Kingdom | June 2017/recruiting | 15 (estimated) | BB305 (βA-T87Q-globin) | G-CSF + plerixafor mPBC | Myeloablative (busulfan) | IV | 31 January 2019 | 31 |
| NCT03432364 | 1/2 | Sangamo Therapeutics and Bioverativ Therapeutics | United States | February 2018/recruiting | 6 | ZFN (ST-400) | mPBCs | Myeloablative (busulfan) | IV | 4 February 2019 | NA |
| NCT03655678 | 1/2 | Vertex Pharmaceuticals and CRISPR Therapeutics | Germany, United Kingdom | September 2018/recruiting | 12 (estimated; may be expanded to 45) | CRISPR/Cas9 (CTX001) | CD34+ human HSPCs (mobilization: NA) | Myeloablative (busulfan) | IV | 3 May 2019 | NA |
| SCD | |||||||||||
| NCT02151526 (HGB205) | 1/2 | bluebird bio | France | July 2013/active, not recruiting | 3 | BB305 (βA-T87Q-globin) | BM | Myeloablative (busulfan) | IV | 31 January 2019 | 37 |
| NCT02186418 | 1/2 | Children’s Hospital Medical Center, Cincinnati | United States, Jamaica | July 2014/recruiting | 10 | sGbG (γ-globin) | BM and plerixafor mPBCs | Reduced intensity conditioning (melphalan 140 mg/m2 BSA) | IV | 6 May 2019 | 44 |
| NCT02247843 | 1 | University of California Children’s Hospital, Los Angeles | United States | July 2014/recruiting | 6 | βAS3-FB (βAS3-globin) | BM | Myeloablative (busulfan) | IV | 29 March 2019 | NA |
| NCT02140554 (HGB206) | 1 | bluebird bio | United States | August 2014/recruiting | 50 (estimated; 3 groups [A, B, C]) | BB305 (βA-T87Q-globin) | BM (A and B) plerixafor mPBCs (C) | Myeloablative (busulfan) | IV | 20 May 2019 | 43 |
| NCT03282656 | 1 | David Williams, Boston Children’s Hospital | United States | February 2018/recruiting | 7 | BCH_BB-LCR shRNA(miR) shRNAmiR | Plerixafor mPBCs | Myeloablative (busulfan) | IV | 24 May 2018 | 54 |
| NCT03745287 | 1/2 | Vertex Pharmaceuticals Incorporated and CRISPR Therapeutics | United States | November 2018/recruiting | 12 (estimated; may be expanded to 45) | CRISPR/Cas9 (CTX001) | NA | Myeloablative (busulfan) | IV | 3 May 2019 | NA |
| Trial number . | Phase . | Sponsor . | Site . | Start date/ recruitment status . | Number of patients . | Vector and transgene (nuclease and DP name) . | Cell source . | Conditioning . | DP administration . | Last update (www.clinicaltrials.gov) . | References . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| β-Thalassemia | |||||||||||
| LG001 | 1/2 | bluebird bio | France | September 2006/completed | 2* | HPV569 (βA-T87Q-globin) | G-CSF mPBCs or BM | Myeloablative (busulfan) | IV | NA | 26 |
| NCT01639690 | 1 | Memorial Sloan Kettering Cancer Center | United States | July 2012/active, not recruiting | 4 | TNS9.3.55 (βA-globin) | G-CSF mPBCs | Nonmyeloablative (busulfan 8 mg/kg) | IV | 6 June 2018 | 113 |
| NCT02151526 (HGB205) | 1/2 | bluebird bio | France | July 2013/active, not recruiting | 4 | BB305 (βA-T87Q-globin) | G-CSF + plerixafor mPBCs | Myeloablative (busulfan) | IV | 31 January 2019 | 28 |
| NCT01745120 (HGB204) | 1/2 | bluebird bio | United States, Australia, Thailand | August 2013/completed | 18 | BB305 (βA-T87Q-globin) | G-CSF + plerixafor mPBCs | Myeloablative (busulfan) | IV | 8 May 2019 | 28 |
| NCT02453477 | 1/2 | IRCCS San Raffaele | Italy | May 2015/active, not recruiting | 10 | GLOBE (βA-globin) | G-CSF + plerixafor mPBCs | Myeloablative (thiotepa + threosulfan) | IO | 4 May 2018 | 33 |
| NCT02906202 (HGB207) | 3 | bluebird bio | United States, France, Germany, Greece, Italy, Thailand, United Kingdom, | July 2016/recruiting | 23 (estimated) | BB305 (βA-T87Q-globin) | G-CSF + plerixafor mPBCs | Myeloablative (busulfan) | IV | 31 January 2019 | 31 |
| NCT02906202 (HGB212) | 3 | bluebird bio | United States, France, Germany, Greece, Italy, Thailand, United Kingdom | June 2017/recruiting | 15 (estimated) | BB305 (βA-T87Q-globin) | G-CSF + plerixafor mPBC | Myeloablative (busulfan) | IV | 31 January 2019 | 31 |
| NCT03432364 | 1/2 | Sangamo Therapeutics and Bioverativ Therapeutics | United States | February 2018/recruiting | 6 | ZFN (ST-400) | mPBCs | Myeloablative (busulfan) | IV | 4 February 2019 | NA |
| NCT03655678 | 1/2 | Vertex Pharmaceuticals and CRISPR Therapeutics | Germany, United Kingdom | September 2018/recruiting | 12 (estimated; may be expanded to 45) | CRISPR/Cas9 (CTX001) | CD34+ human HSPCs (mobilization: NA) | Myeloablative (busulfan) | IV | 3 May 2019 | NA |
| SCD | |||||||||||
| NCT02151526 (HGB205) | 1/2 | bluebird bio | France | July 2013/active, not recruiting | 3 | BB305 (βA-T87Q-globin) | BM | Myeloablative (busulfan) | IV | 31 January 2019 | 37 |
| NCT02186418 | 1/2 | Children’s Hospital Medical Center, Cincinnati | United States, Jamaica | July 2014/recruiting | 10 | sGbG (γ-globin) | BM and plerixafor mPBCs | Reduced intensity conditioning (melphalan 140 mg/m2 BSA) | IV | 6 May 2019 | 44 |
| NCT02247843 | 1 | University of California Children’s Hospital, Los Angeles | United States | July 2014/recruiting | 6 | βAS3-FB (βAS3-globin) | BM | Myeloablative (busulfan) | IV | 29 March 2019 | NA |
| NCT02140554 (HGB206) | 1 | bluebird bio | United States | August 2014/recruiting | 50 (estimated; 3 groups [A, B, C]) | BB305 (βA-T87Q-globin) | BM (A and B) plerixafor mPBCs (C) | Myeloablative (busulfan) | IV | 20 May 2019 | 43 |
| NCT03282656 | 1 | David Williams, Boston Children’s Hospital | United States | February 2018/recruiting | 7 | BCH_BB-LCR shRNA(miR) shRNAmiR | Plerixafor mPBCs | Myeloablative (busulfan) | IV | 24 May 2018 | 54 |
| NCT03745287 | 1/2 | Vertex Pharmaceuticals Incorporated and CRISPR Therapeutics | United States | November 2018/recruiting | 12 (estimated; may be expanded to 45) | CRISPR/Cas9 (CTX001) | NA | Myeloablative (busulfan) | IV | 3 May 2019 | NA |
BM, bone marrow; BSA, body surface area; CRISPR, clustered regularly interspaced short palindromic repeat; DP, drug product; G-CSF, granulocyte-colony stimulating factor; IO, intraosseously; mPBC, mobilized peripheral blood cell; NA, not available; shRNA, short hairpin RNA; ZFN, zinc-finger nuclease.
P1 failed to engraft and received the backup cells.