RAY121 for Immune System Disorders

Recruiting at 76 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment called RAY121 for certain immune system disorders. It targets conditions such as antiphospholipid syndrome (a blood clotting disorder), bullous pemphigoid (skin blistering), Behçet's Syndrome (causing mouth sores and other issues), dermatomyositis (an inflammatory muscle disease), immune-mediated necrotizing myopathy (muscle weakness), and immune thrombocytopenia (low platelet count). All participants will receive multiple doses of the experimental treatment. Ideal candidates are individuals with these conditions who have not found success with other treatments or need more effective options. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance 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 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.

Is there any evidence suggesting that RAY121 is likely to be safe for humans?

Research shows that RAY121, a new type of antibody, has been tested for safety in healthy adults. Earlier studies found it generally well-tolerated, with most participants not experiencing serious side effects. The side effects that did occur were usually mild, such as fatigue or headaches.

This trial is in an early stage, primarily focusing on ensuring the treatment's safety. At this stage, researchers collect information about its safety and side effects. So far, RAY121 appears safe, but more data is needed for certainty. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

RAY121 is unique because it targets immune system disorders in a way that current treatments might not. While many existing therapies focus on suppressing immune responses broadly, RAY121 is designed to modulate the immune system more precisely, potentially reducing unwanted side effects. Researchers are excited about this treatment due to its innovative approach to regulating immune activity, which could offer a more tailored and effective solution for patients with immune system disorders.

What evidence suggests that RAY121 might be an effective treatment for immune system disorders?

Research has shown that RAY121 targets the classical complement pathway, a part of the immune system involved in immune disorders. This drug resembles rituximab, which has effectively treated serious autoimmune diseases. This similarity suggests that RAY121 might also help manage conditions such as antiphospholipid syndrome and bullous pemphigoid. Early animal studies showed promising results, indicating potential benefits for humans. ^{1 4 5 6 7}

Who Is on the Research Team?

Sponsor Chugai Pharmaceutical Co.Ltd

Principal Investigator

[e-mail]

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06371417

Study Details | NCT06371417 | Phase 1b Trial of RAY121 ... This Phase 1b basket trial will investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary efficacy of RAY121, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06723106

Phase 1b Long-term Extension Trial of RAY121 in ... This is a long-term extension trial of RAY121 in patients with immunological diseases such as antiphospholipid syndrome (APS), bullous pemphigoid (BP), ...

3. withpower.com withpower.com/trial/phase-1-purpura-thrombocytopenic-idiopathic-4-2024-99519

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 ...

4. app.trialscreen.org app.trialscreen.org/trials/phase-1-1b-ray121-immunological-diseases-rainbow-trial-nct06371417

A Phase 1b Trial of RAY121 in Immunological Diseases This is a Phase 1b clinical trial, which means that the study drug (RAY121) will be administered to patients with specific autoimmune diseases.

5. ucihealth.org ucihealth.org/clinical-trials/ccr-23-119

phase ib open label basket study of ray121 Official Title: PHASE IB OPEN LABEL BASKET STUDY OF RAY121 TO INHIBIT COMPLEMENT CLASSICAL PATHWAY IN IMMUNOLOGICAL DISEASES (RAINBOW TRIAL).

6. acrabstracts.org acrabstracts.org/abstract/ray121-a-novel-recycling-monoclonal-antibody-against-complement-c1s-safety-pharmacokinetic-and-pharmacodynamic-data-from-a-phase-1a-first-in-human-clinical-trial-in-healthy-adults/

RAY121, a Novel Recycling Monoclonal Antibody Against ... RAY121 is a novel anti-human C1s monoclonal antibody, which shows a longer half-life based on Sequential Monoclonal Antibody Recycling Technology.

7. trials.arthritis.org trials.arthritis.org/trials/NCT06371417

Phase 1b Trial of RAY121 in Immunological Diseases ... This Phase 1b basket trial will investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary efficacy of RAY121, a ...