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

Phase 1

Recruiting

• Conditions: Immune-mediated Necrotizing Myopathy (IMNM); Dermatomyositis (DM); Behçet's Syndrome (BS); Antiphospholipid Syndrome (APS); Bullous Pemphigoid (BP); Immune Thrombocytopenia (ITP)
• Interventions: Drug: RAY121

• Registration Number: NCT06371417
• Lead Sponsor: Chugai Pharmaceutical

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-04-04
• Study First Submitted QC: 2024-04-14
• Study First Posted: 2024-04-17
• Study Start: 2024-08-19
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-19
• Last Update Posted: 2025-05-20
• Primary Completion: 2026-06-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 144

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RAY121	RAY121	All enrolled patients will receive RAY121 multiple dose

Primary Outcome Measures

Name	Time	Method
Adverse events (AEs)	Baseline to Week 32	Incidence, severity, and causal relationship of AEs

Secondary Outcome Measures

Name	Time	Method
RAY121 concentration	Baseline to Week 32	Serum RAY121 concentration
Cmin	Baseline to Week 32	Minimum observed serum concentration (Cmin)
Total C1s	Baseline to Week 32	Total C1s
Complement activity (classical pathway)	Baseline to Week 32	Complement activity (classical pathway)
Anti-RAY121 antibodies	Baseline to Week 32	Titer of anti-RAY121 antibodies
AUCτ	Baseline to Week 32	Area under the concentration-time curve over a dosing interval (AUCτ)
Active C1s	Baseline to Week 32	Active C1s
Cmax	Baseline to Week 32	Maximum observed serum concentration (Cmax)

Trial Locations

Locations (67)

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Nerve and Muscle Center of Texas; 🇺🇸 Houston, Texas, United States

Okayama University Hospital; 🇯🇵 Okayama, Japan

University of California-Irvine; 🇺🇸 Orange, California, United States

Northwell Health, LLC PRIME; 🇺🇸 Lake Success, New York, United States

Hospital for Special Surgery; 🇺🇸 New York, New York, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

University of Pennsylvania, Perelman Center for Advanced Medicine; 🇺🇸 Philadelphia, Pennsylvania, United States

Amarillo Center for Clinical Research; 🇺🇸 Amarillo, Texas, United States

Royal Prince Alfred Hospital; 🇦🇺 Camperdown, New South Wales, Australia

Westmead Hospital; 🇦🇺 Sydney, New South Wales, Australia

Campbelltown Public Hospital; 🇦🇺 Sydney, New South Wales, Australia

The Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia

Box Hill Hospital; 🇦🇺 Melbourne, Victoria, Australia

AKH - Medizinische Universitaet Wien, Abteilung fuer Klinische Pharmakologie; 🇦🇹 Vienna, Austria

Diagnostic Consultation Center CONVEX EOOD; 🇧🇬 Sofia, Sofia City Province, Bulgaria

"SHATHD" EAD Sofia; 🇧🇬 Sofia, Sofia City Province, Bulgaria

UMHAT "Prof. Dr. St. Kirkovich", AD; 🇧🇬 Stara Zagora, Stara Zagora Province, Bulgaria

University of Alberta Hospital - Department of Anesthesiology and Pain Medicine; 🇨🇦 Edmonton, Alberta, Canada

University of Alberta Hospital - Dermatology; 🇨🇦 Edmonton, Alberta, Canada

The Royal Institution for the Advancement of Learning/McGill University; 🇨🇦 Montreal, Quebec, Canada

Centre de Rhumatologie de l'Est du Quebec; 🇨🇦 Rimouski, Quebec, Canada

DIEX Recherche Sherbrooke Inc.; 🇨🇦 Sherbrooke, Quebec, Canada

Clinical Hospital Center "Sestre Milosrdnice"; 🇭🇷 Zagreb, City Of Zagreb, Croatia

University hospital centre Zagreb; 🇭🇷 Zagreb, City Of Zagreb, Croatia

Specialty Hospital Medico; 🇭🇷 Rijeka, Primorje-Gorski Kotar County, Croatia

Sanatorium Profesora Arenbergera; 🇨🇿 Prague, City Of Prague, Czechia

Hopital Lapeyronie,Service d'Immuno Rhumatologie; 🇫🇷 Montpellier, Occitanie, France

AP-HP Hôpital Universitaire Pitié Salpêtrière; 🇫🇷 Paris, Île-de-France, France

Universitaetsklinikum Tuebingen; 🇩🇪 Tuebingen, Baden-Württemberg, Germany

Universitaetsklinikum Erlangen; 🇩🇪 Erlangen, Bavaria, Germany

Universitaetsklinikum Carl Gustav Carus TU Dresden, Klinik und Poliklinik f. Dermatologie; 🇩🇪 Sachsen, Bundesländer, Germany

Universitaetsmedizin Goettingen; 🇩🇪 Göttingen, Göttingen District, Germany

Universitaetsklinikum Schleswig Holstein - Campus Luebeck, Klinik f Dermatologie, Allergologie u Venerologie; 🇩🇪 Luebeck, Schleswig-Holstein, Germany

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont; 🇭🇺 Szeged, Csongrád-Csanád County, Hungary

Semmelweis Egyetem; 🇭🇺 Budapest, Hungary

IRCCS Istituto Scientifico Romagnolo Per Lo Studio Dei Tumori "Dino Amadori" - IRST; 🇮🇹 Meldola, Forlì-Cesena Province, Italy

Istituto Clinico Humanitas; 🇮🇹 Milano, Milan Province, Italy

Ospedale San Giovanni Bosco; 🇮🇹 Torino, Turin Province, Italy

Hokkaido University Hospital; 🇯🇵 Sapporo, Hokkaido, Japan

Tohoku University Hospital; 🇯🇵 Sendai, Miyagi, Japan

Kindai University Hospital; 🇯🇵 Osakasayama, Osaka, Japan

Osaka University Hospital; 🇯🇵 Suita, Osaka, Japan

Hamamatsu University Hospital; 🇯🇵 Hamamatsu, Shizuoka, Japan

National Center of Neurology and Psychiatry; 🇯🇵 Kodaira, Tokyo, Japan

Toho University Omori Medical Center; 🇯🇵 Ota-ku, Tokyo, Japan

University Medical Centre Groningen UMCG; 🇳🇱 Groningen, Groningen Province, Netherlands

UMC Utrecht; 🇳🇱 Utrecht, Utrecht Province, Netherlands

Sorlandet sykehus Kristiansand; 🇳🇴 Kristiansand, Agder County, Norway

Stavanger Universitetssjukehus; 🇳🇴 Stavanger, Rogaland County, Norway

Institute Reumatologii I'm. Eleonory Reicher; 🇵🇱 Warszawa, Masovian Voivodeship, Poland

Centro Clinico Academico Braga; 🇵🇹 Braga, Braga District, Portugal

Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.; 🇵🇹 Vila Nova De Gaia, Porto District, Portugal

Centrul Medical Monza SRL; 🇷🇴 Bucharest, Bucharest Municipality, Romania

Oncology Institute Prof. Dr. Ion Chiricuta I.O.C.N.; 🇷🇴 Cluj-Napoca, Cluj County, Romania

Clinica Universidad de Navarra; 🇪🇸 Pamplona, Community Of Madrid & Navarre, Spain

Hospital Universitario Ramon y Cajal, Servicio de Reumatologia; 🇪🇸 Madrid, Community Of Madrid, Spain

Hospital Universitario 12 de October; 🇪🇸 Madrid, Community Of Madrid, Spain

Hospital Universitari Vall d'Hebron, Internal Medicine Dept.; 🇪🇸 Barcelona, Province Of Barcelona And Catalonia, Spain

Hospital Universitario Reina Sofia; 🇪🇸 Cordoba, Province Of Córdoba, Spain

Hospital Universitari i Politecnic La Fe; 🇪🇸 Valencia, Valencian Community, Spain

Hospital Universitario Virgen del Rocio; 🇪🇸 Sevilla, Province Of Seville, Spain

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Taichung Veterans General Hospital; 🇨🇳 Taipei, Taiwan

Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital; 🇹🇷 Ankara, Ankara Province, Turkey

Istanbul University Istanbul Medical Faculty; 🇹🇷 Istanbul, Istanbul Province, Turkey