RAY121 for Immune System Disorders

Recruiting at 65 trial locations

Overseen By Clinical trials information

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Chugai Pharmaceutical

Must not be taking: Antivirals, Antibiotics, Antifungals, others

Disqualifiers: Cancer, Hepatitis, HIV, Tuberculosis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 32 weeks

144 Participants Needed

Trial Summary

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 that certain treatments are prohibited. It's best to discuss your current medications with the trial team to see if they fall under the prohibited category.

What data supports the effectiveness of the drug RAY121 for immune system disorders?

Research on rituximab, a drug similar to RAY121, shows it can be effective in treating severe autoimmune diseases in children, suggesting potential benefits for immune system disorders. ^{1 2 3 4 5}

What makes the drug RAY121 unique for treating immune system disorders?

RAY121 is unique because it involves the use of IL-12, a cytokine that can modulate the immune system by promoting T helper type 1 (Th1) cell responses, which are crucial for fighting infections and tumors. This mechanism of action is different from many existing treatments, as IL-12 can directly enhance the immune response and potentially overcome immune suppression seen in certain conditions. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial is testing a new drug called RAY121, which aims to help people with certain immune system diseases by blocking a part of the immune system that causes inflammation. The trial will check if the drug is safe and effective for patients with conditions like APS, BP, BS, DM, IMNM, and ITP.

Research Team

Sponsor Chugai Pharmaceutical Co.Ltd

Principal Investigator

[e-mail]

Eligibility Criteria

This trial is for people with certain immune system disorders like low platelet count, antiphospholipid syndrome, dermatomyositis, Behcet's Disease, and bullous pemphigoid. Participants should have one of these conditions to join the study.

Inclusion Criteria

Ability to comply with the study protocol

Signed informed consent form

APS cohort: Established primary APS defined by specific laboratory and clinical criteria

Exclusion Criteria

I have an autoimmune disease that is not the disease this trial is targeting.

I have not received any treatments that are not allowed in this study.

My liver tests are high.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple doses of RAY121 to assess safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy

32 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• RAY121

Trial Overview The RAINBOW Trial is testing a new medication called RAY121 to see if it's safe and how well it works in treating various immunological diseases by inhibiting part of the body's immune response.

Participant Groups

Group I: RAY121 Experimental Treatment 1 Intervention

All enrolled patients will receive RAY121 multiple dose

Who Is Running the Clinical Trial?

Chugai Pharmaceutical

Lead Sponsor

Trials

105

Recruited

25,000+

Dr. Osamu Okuda

Chugai Pharmaceutical

Chief Executive Officer since 2020

MD from Kyoto University

Dr. Mariko Y. Momoi

Chugai Pharmaceutical

Chief Medical Officer

MD from Jichi Medical University

Findings from Research

In a study of 7 children with refractory autoimmune cytopenia, rituximab treatment resulted in a 71% response rate, with 4 patients achieving complete responses and 1 achieving a partial response.

Rituximab was well tolerated, with no serious adverse events reported, and responders experienced a significant reduction in their previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of rituximab in the management of refractory autoimmune cytopenia]. Losa Frías, V., García Sánchez, AM., Ortiz Valentín, I., et al.[2015]

Rituximab, an anti-CD20 monoclonal antibody, showed an acceptable safety profile in a study of 10 pediatric patients with severe autoimmune diseases, although there were serious infections in three patients and one death related to underlying conditions.

The treatment led to significant clinical improvements in nine patients, allowing for a median reduction of 63% in corticosteroid use, with some patients achieving complete discontinuation of steroids, although not all maintained long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effects and safety of rituximab for treatment of refractory pediatric autoimmune diseases. El-Hallak, M., Binstadt, BA., Leichtner, AM., et al.[2019]

A 68-year-old male with squamous cell lung cancer experienced Stevens-Johnson syndrome (SJS) after a single dose of pembrolizumab, but treatment with steroids led to complete remission of his cancer, suggesting that managing immune-related adverse events can be crucial for patient outcomes.

The case highlights the potential role of Nr4a1 mRNA suppression in enhancing antitumor immunity, as changes in immune response markers (like IFN-γ and IL-17) correlated with the patient's recovery, indicating that monitoring these indices could help guide future immunotherapy interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case report involving suppressed nuclear receptor transcription factors 4a1 and Stevens-Johnson syndrome induced by a single dose of pembrolizumab and successfully treated with early steroid administration, resulting in complete remission of stage III lung cancer. Machida, M., Yamazaki, C., Kouda, N., et al.[2022]

A 75-year-old man with metastatic melanoma and myasthenia gravis achieved complete and lasting tumor regression after receiving a combination of pembrolizumab (an immune checkpoint inhibitor) and targeted radiotherapy, despite being on immunosuppressive medications.

This case highlights the complex interactions between immunosuppressive therapies and immune checkpoint inhibitors, suggesting that certain patients with autoimmune conditions may still benefit from immuno-radiotherapy combinations, even after mixed responses to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable Metastatic Melanoma Remission Following Pembrolizumab and Radiotherapy: A Case Report of Prophylactic Immunosuppression in a Patient with Myasthenia Gravis and Immune-Mediated Colitis. Moradi, LA., Clark, CA., Schneider, CS., et al.[2022]

Combining methotrexate (MTX) with biological agents significantly improves the likelihood of achieving a 50% improvement in rheumatoid arthritis symptoms (ACR50) by 32% compared to using biological agents alone, based on a review of 16 trials with 4965 patients.

While the combination therapy may lead to a slightly increased risk of discontinuation due to adverse events (AEs), the overall benefit of improved response rates supports the use of MTX alongside biological treatments for rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Added value of combining methotrexate with a biological agent compared to biological monotherapy in rheumatoid arthritis patients: A systematic review and meta-analysis of randomised trials. Tarp, S., Jørgensen, TS., Furst, DE., et al.[2020]

Recombinant human IL-12 (rhIL-12) has shown promising immunomodulatory effects in treating diseases like cancer and viral infections, based on results from phase I and II clinical trials.

The administration of rhIL-12 has been associated with tolerable toxicities, indicating its potential for safe use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The regulation and activity of interleukin-12. Wang, Y., Fan, KT., Li, JM., et al.[2022]

Interleukin 12 (IL-12) is crucial for promoting Th1 immune responses, which help the body fight off certain infections, but its production and receptor expression must be tightly regulated to prevent excessive immune reactions.

While IL-12 is important for defense against intracellular pathogens, its strong Th1-promoting activity can also lead to autoimmune diseases, highlighting the need for careful control of its activity in the immune system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-12, a key cytokine in Th1-mediated autoimmune diseases. Adorini, L.[2005]

The IL12RB2 gene acts as a tumor suppressor in B cell malignancies, as shown by Il12rb2 knockout mice that spontaneously develop B cell tumors and lung tumors due to impaired IL-12-mediated immunosurveillance.

In Il12rb2 KO mice, endogenous IL-12 led to smaller B16 melanoma tumors with reduced cell proliferation and increased apoptosis, indicating a previously unknown mechanism of IL-12's direct antitumor activity, which could be further enhanced by hydrodynamic delivery of IL-12.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endogenous IL-12 triggers an antiangiogenic program in melanoma cells. Airoldi, I., Di Carlo, E., Cocco, C., et al.[2022]

Targeted inactivation of the Il12rb2 gene in mice led to increased susceptibility to autoimmune diseases and B-cell tumors, indicating that IL-12 plays a crucial role in controlling B-cell activation and preventing tumor formation.

The study found that Il12rb2 knockout mice developed immune-complex glomerulonephritis and various tumors, suggesting that the absence of IL-12 signaling may lead to unchecked B-cell proliferation and associated pathologies, including lung carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of Il12rb2 signaling predisposes to spontaneous autoimmunity and malignancy. Airoldi, I., Di Carlo, E., Cocco, C., et al.[2021]

In children with B-cell acute lymphoblastic leukemia (B-ALL), immune suppression was linked to altered cytokine levels and gene expression associated with immune exhaustion, indicating a challenging tumor microenvironment.

Treatment with recombinant IL-12 (rIL-12) in mouse models of B-ALL restored immune function by increasing pro-inflammatory cytokines and enhancing T-cell activity, suggesting a promising strategy to improve immunotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B-cell acute lymphoblastic leukemia promotes an immune suppressive microenvironment that can be overcome by IL-12. Hunter, R., Imbach, KJ., Zhou, C., et al.[2022]

References

1. Spain pubmed.ncbi.nlm.nih.gov

[Role of rituximab in the management of refractory autoimmune cytopenia]. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

Clinical effects and safety of rituximab for treatment of refractory pediatric autoimmune diseases. [2019]

3. England pubmed.ncbi.nlm.nih.gov

A case report involving suppressed nuclear receptor transcription factors 4a1 and Stevens-Johnson syndrome induced by a single dose of pembrolizumab and successfully treated with early steroid administration, resulting in complete remission of stage III lung cancer. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Durable Metastatic Melanoma Remission Following Pembrolizumab and Radiotherapy: A Case Report of Prophylactic Immunosuppression in a Patient with Myasthenia Gravis and Immune-Mediated Colitis. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Added value of combining methotrexate with a biological agent compared to biological monotherapy in rheumatoid arthritis patients: A systematic review and meta-analysis of randomised trials. [2020]

6. Singapore pubmed.ncbi.nlm.nih.gov

The regulation and activity of interleukin-12. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Interleukin-12, a key cytokine in Th1-mediated autoimmune diseases. [2005]

8. United States pubmed.ncbi.nlm.nih.gov

Endogenous IL-12 triggers an antiangiogenic program in melanoma cells. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Lack of Il12rb2 signaling predisposes to spontaneous autoimmunity and malignancy. [2021]

10. England pubmed.ncbi.nlm.nih.gov

B-cell acute lymphoblastic leukemia promotes an immune suppressive microenvironment that can be overcome by IL-12. [2022]