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

Phase 1b Open-label Basket Trial of RAY121 to Inhibit Classical Complement Pathway in Immunological Diseases (RAINBOW Trial)

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).

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 144
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical trials information; Phone Number: only use Email; Email: clinical-trials@chugai-pharm.co.jp

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Royal Prince Alfred Hospital
    • Sydney, New South Wales, Australia, 2145
      • Recruiting
      • Westmead Hospital
    • Sydney, New South Wales, Australia, 2560
      • Recruiting
      • Campbelltown Public Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • The Alfred Hospital
    • Melbourne, Victoria, Australia, 3128
      • Recruiting
      • Box Hill Hospital
• Austria
  • Vienna, Austria, 1090
    • Not yet recruiting
    • AKH - Medizinische Universitaet Wien, Abteilung fuer Klinische Pharmakologie
• Bulgaria
  • Sofia City Province
    • Sofia, Sofia City Province, Bulgaria, 1202
      • Not yet recruiting
      • Diagnostic Consultation Center CONVEX EOOD
    • Sofia, Sofia City Province, Bulgaria, 1756
      • Not yet recruiting
      • "SHATHD" EAD Sofia
  • Stara Zagora Province
    • Stara Zagora, Stara Zagora Province, Bulgaria, 6003
      • Not yet recruiting
      • UMHAT "Prof. Dr. St. Kirkovich", AD
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Recruiting
      • University of Alberta Hospital - Department of Anesthesiology and Pain Medicine
    • Edmonton, Alberta, Canada, T6G 2G3
      • Recruiting
      • University of Alberta Hospital - Dermatology
  • Quebec
    • Montreal, Quebec, Canada, H3A 0G4
      • Recruiting
      • The Royal Institution for the Advancement of Learning/McGill University
    • Rimouski, Quebec, Canada, G5L 8W1
      • Recruiting
      • Centre de Rhumatologie de l'Est du Quebec
    • Sherbrooke, Quebec, Canada, J1L 0H8
      • Recruiting
      • Diex Recherche Sherbrooke Inc.
• Croatia
  • City of Zagreb
    • Zagreb, City of Zagreb, Croatia, 10000
      • Not yet recruiting
      • Clinical Hospital Center "Sestre Milosrdnice"
    • Zagreb, City of Zagreb, Croatia, 10000
      • Not yet recruiting
      • University Hospital Centre Zagreb
  • Primorje-Gorski Kotar County
    • Rijeka, Primorje-Gorski Kotar County, Croatia, 51000
      • Not yet recruiting
      • Specialty Hospital Medico
• Czechia
  • Prague
    • Prague, Prague, Czechia, 11000
      • Not yet recruiting
      • Sanatorium Profesora Arenbergera
• France
  • Occitanie
    • Montpellier, Occitanie, France, 34295
      • Not yet recruiting
      • Hopital Lapeyronie,Service d'Immuno Rhumatologie
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75013
      • Recruiting
      • AP-HP Hôpital Universitaire Pitié Salpêtrière
• Germany
  • Baden-Wurttemberg
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Not yet recruiting
      • Universitaetsklinikum Tuebingen
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Not yet recruiting
      • Universitaetsklinikum Erlangen
  • Bundesländer
    • Sachsen, Bundesländer, Germany, 1307
      • Not yet recruiting
      • Universitaetsklinikum Carl Gustav Carus TU Dresden, Klinik und Poliklinik f. Dermatologie
  • Göttingen District
    • Göttingen, Göttingen District, Germany, 3075
      • Not yet recruiting
      • Universitaetsmedizin Goettingen
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • Not yet recruiting
      • Universitaetsklinikum Schleswig Holstein - Campus Luebeck, Klinik f Dermatologie, Allergologie u Venerologie
• Hungary
  • Budapest, Hungary, 1083
    • Not yet recruiting
    • Semmelweis Egyetem
  • Csongrád-Csanád County
    • Szeged, Csongrád-Csanád County, Hungary, 6720
      • Not yet recruiting
      • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
• Italy
  • Forlì-Cesena Province
    • Meldola, Forlì-Cesena Province, Italy, 47014
      • Not yet recruiting
      • IRCCS Istituto Scientifico Romagnolo Per Lo Studio Dei Tumori "Dino Amadori" - IRST
  • Milan Province
    • Milan, Milan Province, Italy, 20089
      • Not yet recruiting
      • Istituto Clinico Humanitas
  • Turin Province
    • Torino, Turin Province, Italy, 10154
      • Not yet recruiting
      • Ospedale San Giovanni Bosco
• Japan
  • Okayama, Japan, 700-8558
    • Recruiting
    • Okayama University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-0808
      • Recruiting
      • Hokkaido University Hospital
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
      • Recruiting
      • Tohoku University Hospital
  • Osaka
    • Sayama, Osaka, Japan, 589-8511
      • Not yet recruiting
      • Kindai University Hospital
    • Suita, Osaka, Japan, 565-0871
      • Recruiting
      • Osaka University Hospital
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 431-3192
      • Recruiting
      • Hamamatsu University Hospital
  • Tokyo
    • Kodaira, Tokyo, Japan, 187-8551
      • Recruiting
      • National Center of Neurology and Psychiatry
    • Ōta-ku, Tokyo, Japan, 143-8540
      • Recruiting
      • Toho University Omori Medical Center
• Netherlands
  • Groningen Province
    • Groningen, Groningen Province, Netherlands, 9713 GZ
      • Not yet recruiting
      • University Medical Centre Groningen UMCG
  • Utrecht Province
    • Utrecht, Utrecht Province, Netherlands, 3584 CX
      • Not yet recruiting
      • UMC Utrecht
• Norway
  • Agder County
    • Kristiansand, Agder County, Norway, 4604
      • Not yet recruiting
      • Sorlandet sykehus Kristiansand
  • Rogaland County
    • Stavanger, Rogaland County, Norway, 4011
      • Not yet recruiting
      • Stavanger Universitetssjukehus
• Poland
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-637
      • Recruiting
      • Institute Reumatologii I'm. Eleonory Reicher
• Portugal
  • Braga District
    • Braga, Braga District, Portugal, 471-243
      • Not yet recruiting
      • Centro Clinico Academico Braga
  • Porto District
    • Vila Nova de Gaia, Porto District, Portugal, 4434-502
      • Not yet recruiting
      • Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.
• Romania
  • Bucharest Municipality
    • Bucharest, Bucharest Municipality, Romania, 400015
      • Recruiting
      • Centrul Medical Monza SRL
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 11658
      • Recruiting
      • Oncology Institute Prof. Dr. Ion Chiricuta I.O.C.N.
• Spain
  • Community of Madrid & Navarre
    • Pamplona, Community of Madrid & Navarre, Spain, 28027
      • Not yet recruiting
      • Clinica Universidad de Navarra
  • Madrid
    • Madrid, Madrid, Spain, 28034
      • Not yet recruiting
      • Hospital Universitario Ramon y Cajal, Servicio de Reumatologia
    • Madrid, Madrid, Spain, 28041
      • Not yet recruiting
      • Hospital Universitario 12 de October
  • Province Of Córdoba
    • Córdoba, Province Of Córdoba, Spain, 14004
      • Not yet recruiting
      • Hospital Universitario Reina Sofia
  • Province Of Seville
    • Seville, Province Of Seville, Spain, 41013
      • Recruiting
      • Hospital Universitario Virgen del Rocio
  • Province of Barcelona and Catalonia
    • Barcelona, Province of Barcelona and Catalonia, Spain, 08035
      • Not yet recruiting
      • Hospital Universitari Vall d'Hebron, Internal Medicine Dept.
  • Valencia
    • Valencia, Valencia, Spain, 46026
      • Not yet recruiting
      • Hospital Universitari i Politècnic La Fe
• Taiwan
  • Taipei, Taiwan, 100229
    • Recruiting
    • National Taiwan University Hospital
  • Taipei, Taiwan, 407219
    • Not yet recruiting
    • Taichung Veterans General Hospital
• Turkey (Türkiye)
  • Ankara
    • Ankara, Ankara, Turkey (Türkiye), 06200
      • Not yet recruiting
      • Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital
  • Istanbul
    • Istanbul, Istanbul, Turkey (Türkiye), 34093
      • Not yet recruiting
      • Istanbul University Istanbul Medical Faculty
• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • University of California-Irvine
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Not yet recruiting
      • Johns Hopkins University
  • New York
    • Lake Success, New York, United States, 11042
      • Active, not recruiting
      • Northwell Health, LLC PRIME
    • New York, New York, United States, 10021
      • Active, not recruiting
      • Hospital For Special Surgery
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Not yet recruiting
      • Universtity of North Carolina at Chapel Hill
  • Ohio
    • Columbus, Ohio, United States, 43203
      • Withdrawn
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania, Perelman Center for Advanced Medicine
  • Texas
    • Amarillo, Texas, United States, 79124
      • Active, not recruiting
      • Amarillo Center for Clinical Research
    • Austin, Texas, United States, 78759
      • Recruiting
      • Austin Neuromuscular Center
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • Nerve And Muscle Center Of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RAY121; All enrolled patients will receive RAY121 multiple dose	Drug: RAY121; Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)	Incidence, severity, and causal relationship of AEs	Baseline to Week 32

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Chugai Pharmaceutical
• Investigators: Study Director: Sponsor Chugai Pharmaceutical Co.Ltd, clinical-trials@chugai-pharm.co.jp

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: April 4, 2024
• First Submitted That Met QC Criteria: April 14, 2024
• First Posted (Actual): April 17, 2024

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cytopenia; Musculoskeletal Diseases; Mouth Diseases; Stomatognathic Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Muscular Diseases; Pathologic Processes; Neuromuscular Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Skin Manifestations; Eye Diseases; Hematologic Diseases; Skin Diseases; Blood Coagulation Disorders; Skin Diseases, Vascular; Hemorrhagic Disorders; Skin Diseases, Genetic; Blood Platelet Disorders; Thrombotic Microangiopathies; Uveal Diseases; Vasculitis; Skin Diseases, Vesiculobullous; Myositis; Panuveitis; Purpura, Thrombocytopenic; Purpura; Polymyositis; Thrombocytopenia; Uveitis, Anterior; Uveitis; Hereditary Autoinflammatory Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Hemic and Lymphatic Diseases; Purpura, Thrombocytopenic, Idiopathic; Dermatomyositis; Behcet Syndrome; Antiphospholipid Syndrome; Pemphigoid, Bullous
• Other Study ID Numbers: RAY902CT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform. For further details on Chugai's Data Sharing Policy and how to request access to related clinical study documents, see here (www.chugai-pharm.co.jp/english/profile/rd/ctds_request.html).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No