Phase 1b Trial of RAY121 in Immunological Diseases (RAINBOW Trial)

Study Purpose

This Phase 1b basket trial will investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary efficacy of RAY121, a inhibitor of classical complement pathway, after multiple dose administration in patients with immunological diseases such as antiphospholipid syndrome (APS), bullous pemphigoid (BP), Behçet's Syndrome (BS), dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM) and immune thrombocytopenia (ITP).

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 85 Years
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Signed informed consent form. 2. Age >= 18 and <=75 at the time of signing informed consent form (except for BP; Age >=18 and <= 85 with Karnofsky score >= 60% at screening) 3. Ability to comply with the study protocol. 4. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods. 5. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm. 6. APS cohort: Established primary APS defined by the following criteria (at least one of the laboratory criteria and one of the clinical criteria must be met):

- Laboratory criteria (aPL profile) - Persistently positive lupus anticoagulant (LA) test.

- Persistently positive anticardiolipin (aCL) immunoglobulin G (IgG) isotype.

- Persistently positive anti-beta-2 glycoprotein-1 (aβ2GPI) IgG isotype.

- Clinical criteria.

- Livedoid vasculopathy and presence of skin ulcer.

- Acute/chronic aPL nephropathy.

7. BP cohort:

- 1) Age >= 18 and <= 85 with Karnofsky score >= 60 % - 2) Predominant cutaneous lesions.

- 3) Diagnosis with BP with following assessments positive: - a Positive direct immunofluorescence, and either.

- b Positive indirect immunofluorescence, or.

- c Positive serology on ELISA for BP180 autoantibody.

- 4) Bullous Pemphigoid Disease Area Index (BPDAI) score >= 20.

- 5) Weekly average of daily Peak Pruritus Numerical Rating Score (PP-NRS) >=4.

- 6) Accept to take photograph of bullous lesions.

8. BS cohort:

- 1) Diagnosed with BS.

- 2) Oral ulcers that occurred at least 3 times in the previous 12 month period.

- 3) Have at least 2 oral ulcers over the 4 weeks prior to screening.

- 4) Have at least 2 oral ulcers at Week 0.

- 5) Have prior treatment with at least 1 non-biologic BS therapy.

- 6) Patients who need systemic therapy as whose oral or mucocutaneous ulcers cannot be adequately controlled by topical therapy.

9. DM cohort:

- 1) Diagnosed with definite or probable inflammatory myopathies and categorized as DM.

- 2) Patients with inadequate response to corticosteroids and/or immune-suppressants or intolerance to DM therapies.

- 3) Manual Muscle Test-8 (MMT-8) score < 142, with at least one abnormality in the following Core Set Measures: - Patient Global Activity Visual Analogue Scale (PtGA-VAS) >= 2 cm.

- Physician Global Activity Visual Analogue Scale (PhGA-VAS) >= 2 cm.

- Global extra-muscular activity >= 2 cm.

- At least one muscle enzyme > 1.5 times upper limit of normal (ULN) - Health Assessment Questionnaire (HAQ) >= 0.25.

- 4) Moderate to severe DM defined as CDASI activity score > 14.

10. IMNM cohort:

- 1) Clinically Diagnosed with IMNM as anti-HMGCR myopathy or anti-SRP myopathy.

- 2) Creatine kinase (CK) > 1,000 U/L.

- 3) Patients who have an inadequate response to corticosteroids and/or immunosuppressants or intolerance to IMNM therapies.

- 4) MMT-8 score < 142.

11. ITP cohort:

- 1) Confirmed diagnosis of persistent/chronic ITP based on the following criteria: - ITP defined per the current guidelines.

- Platelet count <= 30 × 10^9/L on 2 consecutive occasions.

- 2) Lack of an sustained adequate platelet count response to a thrombopoietin receptor agonist and at least one other ITP treatment or a second thrombopoietin receptor agonist (TPO-RA) - 3) A history of response with an platelet counts increase more than 20 × 10^9/L from baseline by at least one prior line of therapy.

Exclusion Criteria:

1. History of anaphylaxis or hypersensitivity to a biologic agent. 2. Active infection requiring systemic antiviral, antibiotics or antifungal. 3. Planned surgery during the study. 4. Pregnant or breastfeeding, or intending to become pregnant. 5. Any serious medical condition or abnormality in clinical laboratory tests that precludes the patient's safe participation in and completion of the study. 6. Clinically significant ECG abnormalities. 7. Illicit drug or alcohol abuse. 8. Clinical diagnosis of autoimmune diseases other than the target disease (except for Sjögren's syndrome in DM and IMNM) 9. Positive for hepatitis B surface antigen. 10. Positive for hepatitis C virus antibody. 11. Positive for human immunodeficiency virus antibody. 12. Evidence of current infection with tuberculosis. 13. History of cancer within 5 years. 14. Treatment with investigational therapy within 28 days or 5 half-lives. 15. Previous and current treatment with anti-C1s antibody at any time. 16. Other complement inhibitors within 3 months. 17. Patients who receive any treatments which fall into the Prohibited Therapy Criteria. 18. Patients with an elevated alanine aminotransferase or aspartate aminotransferase > 1.5 × ULN in combination with an elevated total bilirubin > 1.5 × ULN. 19. APS cohort:

- 1) APS associated with other systemic autoimmune disease.

- 2) Acute thrombosis (arterial or venous acute thrombosis diagnosis) within 30 days before screening.

- 3) Patients with thrombotic APS without any anticoagulation treatment.

- 4) Treatment with prohibited medications.

20. BP cohort:

- 1) Initiation of treatment with or increase in the dose of systemic or topical corticosteroid within 2 weeks.

- 2) Current treatment with a drug that may cause or exacerbate BP unless the dose has been stable.

- 3) Initiation of treatment with topical calcineurin inhibitor, or topical phosphodiesterase (PDE) 4 inhibitor within 7 days.

- 4) Treatment with prohibited medications.

21. BS cohort:

- 1) BS-related active major organ involvement-ocular lesions requiring immunosuppressive therapy, pulmonary (e.g., pulmonary artery aneurysm), vascular (e.g., thrombophlebitis), gastrointestinal (e.g., ulcers along the gastrointestinal tract), and central nervous systems (e.g., meningoencephalitis) manifestations.

- 2) History of venous or arterial thrombosis within 1 year.

- 3) Treatment with prohibited medications.

22. DM cohort:

- 1) PhGA-VAS improvement >= 3, or clinically relevant improvement between screening and baseline.

- 2) Overlap myositis (except for overlap with Sjögren's syndrome), connective tissue disease associated DM, inclusion body myositis, polymyositis, IMNM, juvenile DM or drug-induced myopathy.

- 3) Cancer-associated myositis.

- 4) Significant muscle damage.

- 5) Past history of severe Interstitial lung disease flare, severe non-infectious lung inflammation which required active intervention, or multiple episodes of lung disease.

- 6) Severe respiratory muscle weakness.

- 7) Severe bulbar palsy.

- 8) Treatment with prohibited medications.

23. IMNM cohort:

- 1) PhGA-VAS improvement >= 3, or clinically relevant improvement between screening and baseline.

- 2) Overlap myositis (except for overlap with Sjögren's syndrome), connective tissue disease associated DM, inclusion body myositis, polymyositis, juvenile DM or druginduced myopathy.

- 3) Cancer-associated myositis.

- 4) Significant muscle damage.

- 5) Past history of severe Interstitial lung disease (ILD) flare, severe non-infectious lung inflammation which required active intervention, or multiple episodes of lung disease.

- 6) Severe respiratory muscle weakness.

- 7) Severe bulbar palsy.

- 8) Treatment with prohibited medications.

24. ITP cohort:

- 1) Secondary ITP.

- 2) Clinical diagnosis or history of Myelodysplastic Syndrome or autoimmune hemolytic anemia.

- 3) History of venous or arterial thrombosis within 12 months.

- 4) Patients who experienced major bleeding within 4 weeks.

- 5) Treatment with prohibited medications.

- 6) Any laboratory test results meet either of the following criteria at screening: - Hemoglobin <10 g/dL.

- Thyroid-stimulating hormone >= 10 μIU/mL

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06371417
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Chugai Pharmaceutical
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Sponsor Chugai Pharmaceutical Co.Ltd
Principal Investigator Affiliation	[email protected]
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Australia, Austria, Bulgaria, Canada, Croatia, Czechia, France, Germany, Hungary, Italy, Japan, Netherlands, Norway, Poland, Portugal, Romania, Spain, Taiwan, Turkey (Türkiye), United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Antiphospholipid Syndrome (APS), Bullous Pemphigoid (BP), Behçet's Syndrome (BS), Dermatomyositis (DM), Immune-mediated Necrotizing Myopathy (IMNM), Immune Thrombocytopenia (ITP)

Arms & Interventions

Arms

Experimental: RAY121

All enrolled patients will receive RAY121 multiple dose

Interventions

Drug: - RAY121

Injection

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of California-Irvine, Orange 5379513, California 5332921

Status

Recruiting

Address

University of California-Irvine

Orange 5379513, California 5332921, 92868

Site Contact

Clinical Trial Finder