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Phase 1CompletedNCT05210530

VCTX210: first CRISPR-edited, device-encapsulated stem-cell islet product

First-in-human Phase 1 trial of VCTX210 — gene-edited, stem-cell-derived pancreatic cells in an implanted device, designed to make insulin without immunosuppression. Completed 2023 as a 7-patient safety study; no efficacy results published. It was the proof-of-concept predecessor to the more heavily edited VCTX211/CTX211 program.

Primary endpoints

  • Incidence of adverse events with causality related to the VCTX210A units and/or the surgical implantation/explantation procedures, assessed through 6 months post-implantation

Results so far

No results were posted to the trial registry and no peer-reviewed efficacy results have been published. As a small, open-label safety study its purpose was to establish tolerability of the gene-edited cells and the implant procedure, and to gather early immune-evasion data to inform the next-generation product (VCTX211/CTX211). Company statements indicate the program advanced to that more heavily edited successor rather than reporting standalone VCTX210 outcomes.

The full picture

What it is and why it matters. VCTX210 was the first time a CRISPR gene-edited, stem-cell-derived cell therapy was put into a person to treat type 1 diabetes.1 The idea behind every cell-replacement cure for T1D is to give the body new insulin-making cells. The hard part is that the immune system attacks them — both the original autoimmune attack of T1D and the rejection of any "foreign" donor cells — which normally forces patients onto lifelong immune-suppressing drugs.2 VCTX210 tried to solve that with gene editing instead of drugs.3

How it works. Scientists at CRISPR Therapeutics and ViaCyte started with a master stem-cell line (CyT49), matured it into pancreatic precursor cells, and used CRISPR/Cas9 to make those cells "invisible" to the immune system.4 The edits knocked out the B2M gene (removing the HLA class I flags the immune system uses to spot foreign cells) and added PD-L1 and HLA-E, two signals that calm immune cells down.5 The cells were then loaded into a small, durable, removable implant — a perforated "open" device (the same PEC-Direct / VC-02 design) that lets blood vessels grow in and feed the cells directly.6 The goal was insulin production with no immunosuppression.7

Who it was for and how it was designed. This was a Phase 1, first-in-human, open-label safety study (no placebo, no randomization) in adults 18–65 who had lived with T1D for at least 5 years.8 It enrolled 7 participants at three Canadian sites — Edmonton, Vancouver and Toronto.9 It ran from January 2022 to January 2023 and is now completed.10 The main question was simply safety: how many side effects were caused by the implanted cells or the surgery itself over the first 6 months.11

Key results. Because this was an early safety trial, no efficacy results (such as restored insulin production) were posted to the registry, and no peer-reviewed results paper has been published.12 Its real value was as a proof-of-concept and a stepping stone.13

What it means and what's next. VCTX210 opened the door to its successor, VCTX211, which carries more gene edits (additional knockouts and inserts to improve cell survival and immune evasion) and entered its own trial.14 In 2022 Vertex Pharmaceuticals acquired ViaCyte, folding this hypoimmune islet work into a larger diabetes cell-therapy pipeline that has continued as the CTX211 program.15

References

  1. CRISPR Therapeutics & ViaCyte. CRISPR Therapeutics and ViaCyte Announce First Patient Dosed in Phase 1 Clinical Trial of Novel Gene-Edited Cell Replacement Therapy for T1D. Press release (2022). https://crisprtx.com/about-us/press-releases-and-presentations/crispr-therapeutics-and-viacyte-inc-announce-first-patient-dosed-in-phase-1-clinical-trial-of-novel-gene-edited-cell-replacement-therapy-for-treatment-of-type-1-diabetes-t1d ↩

  2. Karpov DS, et al. Challenges of CRISPR/Cas-Based Cell Therapy for Type 1 Diabetes: How Not to Engineer a "Trojan Horse". Int J Mol Sci (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC10743607/ ↩

  3. CRISPR Therapeutics & ViaCyte. First Patient Dosed press release (2022). https://crisprtx.com/about-us/press-releases-and-presentations/crispr-therapeutics-and-viacyte-inc-announce-first-patient-dosed-in-phase-1-clinical-trial-of-novel-gene-edited-cell-replacement-therapy-for-treatment-of-type-1-diabetes-t1d ↩

  4. Philippidis A. Sweet Spot: CRISPR Therapeutics, ViaCyte Dose First Patient with Cell Therapy for Type 1 Diabetes. GEN (2022). https://www.genengnews.com/gen-edge/sweet-spot-crispr-therapeutics-viacyte-dose-first-patient-with-cell-therapy-for-type-1-diabetes/ ↩

  5. Philippidis A. Vertex to Acquire ViaCyte for $320M, Growing Diabetes Cell Therapy Pipeline. GEN (2022). https://www.genengnews.com/metabolic-disorders/diabetes/vertex-to-acquire-viacyte-for-320m-growing-diabetes-cell-therapy-pipeline/ ↩

  6. Philippidis A. Sweet Spot. GEN (2022). https://www.genengnews.com/gen-edge/sweet-spot-crispr-therapeutics-viacyte-dose-first-patient-with-cell-therapy-for-type-1-diabetes/ ↩

  7. Philippidis A. Sweet Spot. GEN (2022). https://www.genengnews.com/gen-edge/sweet-spot-crispr-therapeutics-viacyte-dose-first-patient-with-cell-therapy-for-type-1-diabetes/ ↩

  8. ClinicalTrials.gov. An Open-Label, First-In-Human Study Evaluating the Safety and Tolerability of VCTX210A Combination Product in Subjects With Type 1 Diabetes Mellitus (NCT05210530). U.S. National Library of Medicine (2023). https://clinicaltrials.gov/study/NCT05210530 ↩

  9. ClinicalTrials.gov. NCT05210530 record (2023). https://clinicaltrials.gov/study/NCT05210530 ↩

  10. ClinicalTrials.gov. NCT05210530 record (2023). https://clinicaltrials.gov/study/NCT05210530 ↩

  11. ClinicalTrials.gov. NCT05210530 record (2023). https://clinicaltrials.gov/study/NCT05210530 ↩

  12. ClinicalTrials.gov. NCT05210530 record — no results posted (2023). https://clinicaltrials.gov/study/NCT05210530 ↩

  13. Karpov DS, et al. Int J Mol Sci (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC10743607/ ↩

  14. Karpov DS, et al. Int J Mol Sci (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC10743607/ ↩

  15. Philippidis A. Vertex to Acquire ViaCyte for $320M. GEN (2022). https://www.genengnews.com/metabolic-disorders/diabetes/vertex-to-acquire-viacyte-for-320m-growing-diabetes-cell-therapy-pipeline/ ↩