EXG34217 for Bone Marrow Failure Syndrome

Overseen By Minako Koga

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Elixirgen Therapeutics, Inc.

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: Completed in prior study

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called EXG34217 for individuals with bone marrow failure syndrome. The goal is to build on previous research to assess the long-term safety and effectiveness of this experimental treatment. The treatment uses a type of stem cell (CD34+ cells) modified outside the body. The trial seeks participants who have completed a specific earlier study and are willing to continue with this follow-up research. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that EXG34217 is likely to be safe for humans?

Research has shown that EXG34217, a treatment for bone marrow failure, was safe in earlier studies. Published results from studies involving patients with telomere biology disorders reported no safety issues related to the treatment. This suggests the treatment is well-tolerated so far. However, these findings come from early research, and ongoing studies aim to confirm these results over a longer period. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

EXG34217 is unique because it involves using autologous CD34+ cells, which are the patient's own stem cells, contacted ex vivo with EXG-001. This approach could offer a more personalized treatment by enhancing the body's natural ability to regenerate healthy blood cells. Unlike traditional treatments for bone marrow failure syndrome, which often involve bone marrow transplants or immunosuppressive therapy, EXG34217 aims to directly rejuvenate the patient's blood-forming cells. Researchers are excited because this could potentially lead to improved outcomes and fewer complications compared to the current standard of care.

What evidence suggests that EXG34217 might be an effective treatment for Bone Marrow Failure Syndrome?

Research has shown that EXG34217, the treatment under study in this trial, could help treat Bone Marrow Failure Syndrome and related telomere disorders. Earlier studies examined its safety and tolerability for patients with these conditions. In this trial, EXG34217 uses a patient's own cells, treated outside the body and then reintroduced. This method aims to improve telomere issues, which are crucial for producing healthy blood cells. Although more research is needed, early results suggest this treatment might benefit people with these rare conditions. ^{2 6 7 8 9}

Who Is on the Research Team?

Kasiani Myers, MD

Principal Investigator

Cincinnati Children Hospital Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with Bone Marrow Failure Syndrome, Pancytopenia, or Telomere Biology Disorders who have completed a previous study (EXG-US-01) and are willing to follow the new study's procedures.

Inclusion Criteria

Signed an Institutional Review Board (IRB) approved informed consent document indicating that they understand the purpose of, and procedures required by the study and are willing to participate in the study and comply with all study procedures and restrictions. Informed consent must be obtained from the subject prior to initiating procedures.

Have completed the 12-month visit of Study EXG-US-01.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants received EXG34217 treatment in the previous study EXG-US-01

Completed in prior study

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 years

Every 6 months for 3 years, then annually for 2 years

What Are the Treatments Tested in This Trial?

Interventions

• EXG34217

Trial Overview The intervention being studied is EXG34217. This trial serves as a long-term follow-up from an earlier Phase I/II study to monitor ongoing effects and gather more data on safety and efficacy.

How Is the Trial Designed?

Group I: EXG34217 Experimental Treatment 1 Intervention

single autologous CD34+ cells contacted ex vivo with EXG-001

Who Is Running the Clinical Trial?

Elixirgen Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

60+

Published Research Related to This Trial

In a phase 2 trial involving 51 patients with myelofibrosis who were intolerant to ruxolitinib, 43.2% of those treated with the novel JAK inhibitor jaktinib showed a significant reduction in spleen volume after 24 weeks.

Jaktinib also improved symptoms related to myelofibrosis, with 61.8% of patients experiencing a notable decrease in total symptom scores, although it was associated with some serious adverse events, including anemia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are intolerant to ruxolitinib: A single-arm, open-label, phase 2, multicenter study. Zhang, Y., Zhou, H., Duan, M., et al.[2023]

Ruxolitinib, an oral JAK1/JAK2 inhibitor, has been the standard treatment for intermediate or high-risk myelofibrosis (MF) since its FDA approval in 2011, demonstrating significant efficacy in improving patient outcomes based on data from the phase 3 COMFORT trials.

The review highlights the importance of dose optimization and management of common side effects, such as anemia and thrombocytopenia, to maximize the safety and clinical benefits of ruxolitinib, supported by findings from subsequent trials like JUMP, ROBUST, EXPAND, and REALISE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety. Verstovsek, S., Mesa, RA., Livingston, RA., et al.[2023]

In a phase 3b study involving 161 patients with polycythemia vera resistant or intolerant to hydroxyurea, ruxolitinib demonstrated a safety profile consistent with previous studies, with 37.9% of patients experiencing adverse events that required dose adjustments.

Ruxolitinib was effective, achieving hematocrit control in 45.3% of patients and significant spleen size reduction in 86.7%, indicating its potential as a viable treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy findings from the open-label, multicenter, phase 3b, expanded treatment protocol study of ruxolitinib for treatment of patients with polycythemia vera who are resistant/intolerant to hydroxyurea and for whom no alternative treatments are available. Foltz, L., Pica, GM., Zerazhi, H., et al.[2021]

In a study of 14 patients with myelofibrosis who received allogeneic hematopoietic cell transplantation after treatment with ruxolitinib, 71.4% experienced relief from myelofibrosis-related symptoms, and 64% had a significant reduction in spleen size.

Ruxolitinib treatment prior to transplantation was associated with a high engraftment rate of 93% and may improve outcomes by reducing inflammatory cytokines, potentially lowering the risk of graft failure and acute graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic cell transplantation for myelofibrosis in patients pretreated with the JAK1 and JAK2 inhibitor ruxolitinib. Jaekel, N., Behre, G., Behning, A., et al.[2021]

Ruxolitinib, a JAK1/JAK2 inhibitor, was evaluated in a large phase 3b study (N = 2233) for treating myelofibrosis, including patients with low platelet counts, showing significant reductions in spleen size and symptoms.

The safety profile of ruxolitinib was consistent with previous studies, with common adverse events like anemia and thrombocytopenia, but these rarely led to treatment discontinuation, indicating it is a viable option for patients with low platelet counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary analysis of JUMP, a phase 3b, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis, including those with low platelet counts. Al-Ali, HK., Griesshammer, M., Foltz, L., et al.[2021]

Citations

1. withpower.com withpower.com/trial/phase-1-bone-marrow-failure-disorders-6-2023-9821a

EXG34217 for Bone Marrow Failure Syndrome This trial is for individuals with Bone Marrow Failure Syndrome, Pancytopenia, or Telomere Biology Disorders who have completed a previous study (EXG-US-01) and ...

2. synapse.patsnap.com synapse.patsnap.com/article/elixirgen-therapeutics-gets-rare-pediatric-disease-status-for-exg-34217-in-dyskeratosis-congenita-and-telomere-disorders

Elixirgen Therapeutics Gets Rare Pediatric Disease Status ... ... bone marrow failure and other serious health conditions,” Ko stated. ... of diseases and the potential effectiveness of EXG-34217. RPDD is ...

3. clinconnect.io clinconnect.io/trials/NCT04211714

Study to Evaluate of EXG34217 in Patients With Telomere This is a Phase I/II, open label, single center study to assess the safety and tolerability of EXG34217 in bone marrow failure patients with telomere biology ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/condition/1008/telomeres

Telomeres Clinical Research Trials Study to Evaluate of EXG34217 in Patients With Telomere Biology Disorders With Bone Marrow Failure. This is a Phase I/II, open label study in up to 12 ...

5. biospace.com biospace.com/fda-approves-elixirgen-therapeutics-ind-application-for-therapy-for-telomere-biology-disorders-with-bone-marrow-failure

FDA Approves Elixirgen Therapeutics IND Application for ... EXG34217 is an autologous cell therapy for telomere biology disorders with bone marrow failure. The FDA's approval allows Elixirgen Therapeutics ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04211714

NCT04211714 | Study to Evaluate of EXG34217 in Patients ... This is a Phase I/II, open label, single center study to assess the safety and tolerability of EXG34217 in bone marrow failure patients with telomere biology ...

7. elixirgentx.com elixirgentx.com/elixirgen-therapeutics-publishes-early-results-showing-telomere-elongation-in-first-gene-therapy-trial-for-telomere-biology-disorders/

Elixirgen Therapeutics Publishes Early Results Showing ... ... EXG-34217 in patients with TBDs with bone marrow failure. Key study highlights include: Published results are from two patients following ...

8. empr.com empr.com/news/telomere-biology-disorder-treatment-gets-orphan-drug-designation/

Telomere Biology Disorder Treatment Gets Orphan Drug ... ... bone marrow failure. EXG-34217 consists of a single dose of autologous CD34+ hematopoietic stem cells that express ZSCAN4 (Zinc finger and ...

9. scienceblog.cincinnatichildrens.org scienceblog.cincinnatichildrens.org/first-gene-therapy-trial-for-telomere-biology-disorders-shows-promising-results/

First Gene Therapy Trial for Telomere Biology Disorders ... ... EXG-34217. Also, no treatment-related safety ... bone marrow failure related to Shwachman Diamond syndrome and dyskeratosis congenita.