TRX103 for Crohn's Disease

Recruiting at 11 trial locations

Overseen By Marco Londei, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Tr1X, Inc.

Must be taking: Corticosteroids

Must not be taking: Investigational agents

Disqualifiers: Organ transplant, HIV, Hepatitis B, others

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

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TRX103 for people with Crohn's Disease. The goal is to determine the safety and effectiveness of different TRX103 doses for this condition. Participants will receive either TRX103 or a combination treatment that includes Cyclophosphamide (a chemotherapy drug) for comparison. Suitable candidates for this trial have moderate to severe Crohn's Disease, experience frequent diarrhea or abdominal pain, and have tried at least two other unsuccessful treatments. As a Phase 1 trial, this research focuses on understanding how TRX103 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 protocol does not specify if you must stop taking your current medications, but it mentions a 'washout period' for any approved treatment for Crohn's Disease before starting the trial. It's best to discuss your current medications with the trial team to understand any specific requirements.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that TRX103, which uses special T cells from healthy donors, is being tested for safety and effectiveness in people with Crohn's Disease. Early results indicate that it is generally safe and well-tolerated by the first two groups of patients.

Cyclophosphamide, a drug already approved by the FDA for other uses, has a well-established safety profile, although individual reactions can differ.

Both treatments have demonstrated evidence of safety, but clinical trials aim to gather more detailed information on their safety and effectiveness for specific conditions like Crohn's Disease. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TRX103 for Crohn's Disease because it introduces a novel mechanism of action that distinguishes it from current treatments like biologics and immunosuppressants. Unlike standard therapies that broadly suppress the immune system, TRX103 targets specific pathways involved in the inflammatory process, potentially offering a more precise treatment with fewer side effects. Additionally, combining TRX103 with cyclophosphamide in different dosing levels allows for personalized treatment approaches, which might enhance effectiveness and improve patient outcomes. This innovative strategy could revolutionize how Crohn's Disease is managed, providing new hope for those who don't respond well to existing options.

What evidence suggests that this trial's treatments could be effective for Crohn's Disease?

Research has shown that TRX103 is a promising new treatment for Crohn's Disease. This treatment uses a special type of cell therapy designed to target the gut, reduce inflammation, and aid in tissue healing. Participants in this trial will receive varying doses of TRX103, with some cohorts also undergoing conditioning. Early results from initial patient groups indicated that the treatment is safe and remains active in the body. Although still under study, these early findings suggest TRX103 could be effective for individuals with moderate to severe Crohn's Disease. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with moderate to severe Crohn's Disease, confirmed by endoscopy and biological evidence. Participants must have a history of the disease for at least a year, weigh over 40 kg, and not be pregnant or planning pregnancy during the study. They should have failed two advanced therapies and cannot have certain infections or recent surgeries.

Inclusion Criteria

I do not have any ongoing serious infections.

My Crohn's disease is active, with significant inflammation and daily symptoms.

I weigh at least 40 kg.

Exclusion Criteria

Subjects that are pregnant, breast feeding, or aim to become pregnant during the study period

I do not have active infections, TB, or specific types of colitis.

Received another investigational agent or therapy within specified timeframe or have not recovered from treatment related toxicities

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TRX103 at various dose levels to evaluate safety and preliminary efficacy

12 weeks

Weekly visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular visits at 3, 6, and 12 months post-infusion

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• TRX103

Trial Overview The trial is testing TRX103's safety and effectiveness in different doses for treating Crohn's Disease compared to Cyclophosphamide. It aims to determine how well TRX103 works in those who haven't responded well to other treatments.

How Is the Trial Designed?

Group I: Cohort 3A Experimental Treatment 2 Interventions

Dose level 3 with conditioning

Group II: Cohort 3 Experimental Treatment 1 Intervention

Dose level 3

Group III: Cohort 2A Experimental Treatment 2 Interventions

Dose level 2 with conditioning

Group IV: Cohort 2 Experimental Treatment 1 Intervention

Dose level 2

Group V: Cohort 1 Experimental Treatment 1 Intervention

Dose level 1

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Tr1X, Inc.

Lead Sponsor

Trials

2

Recruited

60+

Published Research Related to This Trial

Cyclophosphamide, introduced in 1958, is a potent immunosuppressive agent used to treat various diseases, both malignant and non-malignant.

Despite its therapeutic benefits, cyclophosphamide is associated with significant urologic complications, including hemorrhagic cystitis, vesical fibrosis, and an increased risk of urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bladder carcinoma following cyclophosphamide therapy. A case report. Kiesswetter, H., Baloch, N., Flamm, J.[2019]

In a study of 27 patients with advanced Ewing's sarcoma, the combination of cyclophosphamide and hydroxycamptothecin as second-line chemotherapy showed a 30% overall response rate and an 82% disease control rate, indicating its potential effectiveness in managing this aggressive cancer.

The treatment was associated with manageable side effects, with severe toxicities occurring in a minority of cycles, suggesting that the CTX-HCPT regimen is tolerable for patients, although further research is needed to fully confirm its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclophosphamide-hydroxycamptothecin as second-line chemotherapy for advanced Ewing's sarcoma: experience of a single institution. Han, K., Sun, Y., Zhang, J., et al.[2014]

Ewing's sarcoma and primitive peripheral neuroectodermal tumor cell lines showed high sensitivity to several anti-tumor agents, particularly cytosine arabinoside (ARA-C), which was effective at concentrations significantly lower than typical clinical doses.

The study suggests that manipulating the IGF-I signaling pathway could enhance the sensitivity of these tumor cells to chemotherapy, indicating a potential strategy for improving treatment outcomes in patients with these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin-like growth factor-I-dependent growth and in vitro chemosensitivity of Ewing's sarcoma and peripheral primitive neuroectodermal tumour cell lines. Hofbauer, S., Hamilton, G., Theyer, G., et al.[2019]

The combination of β-glucan from Candida albicans (CAIBG) and cyclophosphamide (CTX) effectively reduces tumor growth and prolongs survival in S180 tumor-bearing mice, suggesting a potential synergistic effect in cancer treatment.

CAIBG appears to mitigate the immunosuppressive effects of CTX, as indicated by improved spleen and thymus indices and increased levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the combined treatment group compared to CTX alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined use of insoluble β-glucan from the cell wall of Candida albicans and cyclophosphamide: Validation in S180 tumor-bearing mice. Qi, Y., Hu, X., Cui, J., et al.[2019]

The combination of topotecan and cyclophosphamide (TC) was found to be tolerable in adults with recurrent sarcoma, but it showed only modest effectiveness, with a median time to progression of 2.5 months and limited partial responses in some patients.

Hematologic toxicity was a significant concern, with nearly half of the patients requiring blood transfusions and a third experiencing fever and neutropenia, highlighting the need for alternative treatment options for this high-risk group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan and cyclophosphamide in adults with relapsed sarcoma. Blanchette, P., Hogg, D., Ferguson, P., et al.[2021]

In a study involving 28 patients with resistant pediatric solid tumors, high-dose cyclophosphamide and topotecan (HD-Cy/Topo) demonstrated promising antitumor effects while maintaining normal cardiac, renal, hepatic, and pulmonary function, indicating a favorable safety profile.

Despite profound myelosuppression being the major toxicity observed, the treatment allowed for retreatment by day 28 and showed partial or minor responses in various tumor types, suggesting HD-Cy/Topo could be a valuable option in aggressive salvage therapy for resistant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of topotecan and high-dose cyclophosphamide for resistant pediatric solid tumors. Kushner, BH., Kramer, K., Meyers, PA., et al.[2019]

Ewing tumours, which are common malignant bone tumours in children, have a specific chromosomal rearrangement that contributes to their cancerous behavior, and treatments involving multidrug chemotherapy can lead to over 50% long-term survival in localized cases.

Patients with metastases at diagnosis or those who do not respond to initial therapy have a significantly worse prognosis, highlighting the importance of specialized care and the potential benefits of participating in clinical trials for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ewing tumour: incidence, prognosis and treatment options. Paulussen, M., Fröhlich, B., Jürgens, H.[2018]

In a study involving 36 patients, Endoxan showed significantly higher peak plasma concentrations of cyclophosphamide compared to Cytoxan and an investigational tablet, indicating it may be more effective in delivering the drug quickly.

While all formulations had similar bioavailability and toxicity profiles, the investigational formulation was associated with slightly lower overall toxicity, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology, relative bioavailability, and toxicity of three different oral cyclophosphamide preparations in a randomized, cross-over study. Stewart, DJ., Morgan, LR., Verma, S., et al.[2019]

A combination treatment of cyclophosphamide (CTX) and interferon-beta (IFN-beta) in patients with rapidly worsening multiple sclerosis showed significant long-term benefits, maintaining reduced relapse rates and disability progression for 36 months after treatment cessation.

The study demonstrated that this treatment was not only effective but also safe, with no significant side effects reported, making it a viable option for patients who do not respond to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stabilization of rapidly worsening multiple sclerosis for 36 months in patients treated with interferon beta plus cyclophosphamide followed by interferon beta. Patti, F., Reggio, E., Palermo, F., et al.[2018]

In a study on mice, epigallocatechin-3-gallate (EGCG) from green tea was found to significantly improve gut recovery after cyclophosphamide (CTX) treatment, which typically causes severe gastrointestinal damage.

EGCG not only restored intestinal structure and tight junction protein levels but also reduced inflammation and oxidative stress, suggesting it could be a promising strategy to mitigate CTX-induced gastrointestinal toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(-)-Epigallocatechin-3-gallate mitigates cyclophosphamide-induced intestinal injury by modulating the tight junctions, inflammation and dysbiosis in mice. Wei, R., Liu, X., Wang, Y., et al.[2022]

Citations

1. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT06721962

Treatment of Moderate to Severe Refractory Crohn's Disease This research study is testing an investigational research product called TRX103 as a possible treatment for individuals suffering from Crohn's Disease (CD).

2. cgtlive.com cgtlive.com/view/tr1-treg-therapy-trial-crohn-disease

Tr1 Treg Therapy to be Evaluated in Trial for Crohn Disease The study will evaluate the safety, tolerability, and clinical activity of TRX-103 in participants with moderate to severe CD that has failed 3 or more ...

3. withpower.com withpower.com/trial/trx103-for-crohns-disease-a3520

TRX103 for Crohn's Disease This research study is testing an investigational research product called TRX103 as a possible treatment for individuals suffering from Crohn's Disease (CD).

4. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/tr1x-awarded-8m-grant-for-trx103-gvhd-trial/

TR1X Awarded $8M Grant for TRX103 GvHD Trial Initial data from the first two patient cohorts indicate positive persistence and safety profiles, with further data expected in 2025. TRX103 is ...

5. synapse.patsnap.com synapse.patsnap.com/article/fda-clears-tr1xs-ind-for-trx103-a-tr1-treg-therapy-for-refractory-crohnE28099s-disease

FDA Clears Tr1X's IND for TRX103, a Tr1 Treg Therapy ... TRX103 represents a pioneering Type 1 Treg (Tr1) cell therapy, explicitly intended to target the gut, mitigate inflammation, promote tissue ...

6. cdclinicaltrial.com cdclinicaltrial.com/

Crohn's Clinical Trial TRX103 is the current name of an investigational therapy that contains a modified set of T cells from a healthy donor that mimic regulatory T cells. Regulatory ...

7. delta.larvol.com delta.larvol.com/Products/?ProductId=67e7526a-2c81-4090-a3ee-f4e5b24a4511

TRX103 / Tr1X Development of allogeneic engineered type I regulatory T cells (TRX103) to modulate inflammation and pathogenic T cells in refractory Crohn's disease.

8. biospace.com biospace.com/press-releases/tr1x-awarded-8-million-cirm-grant-to-support-trx103-phase-1-2a-clinical-trial-for-graft-versus-host-disease

Tr1X Awarded $8 Million CIRM Grant to Support TRX103 ... ... TRX103. The Company has reported positive initial persistence and safety data in the first two patient cohorts, with additional data ...