Clinical trial NCT06371417: Phase 1b Trial of RAY121 in Immunological Diseases (RAINBOW Trial)
Official title: Phase 1b Open-label Basket Trial of RAY121 to Inhibit Classical Complement Pathway in Immunological Diseases (RAINBOW Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Antiphospholipid Syndrome (APS)
Bullous Pemphigoid (BP)
Behçet's Syndrome (BS)
Dermatomyositis (DM)
Immune-mediated Necrotizing Myopathy (IMNM)
Immune Thrombocytopenia (ITP)
Lead sponsor: Chugai Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2024-04-17
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility 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

Primary outcomes:
measure: Adverse events (AEs)
timeFrame: Baseline to Week 32
Secondary outcomes:
measure: RAY121 concentration
timeFrame: Baseline to Week 32
measure: AUCτ
timeFrame: Baseline to Week 32
measure: Cmax
timeFrame: Baseline to Week 32
measure: Cmin
timeFrame: Baseline to Week 32
measure: Active C1s
timeFrame: Baseline to Week 32
measure: Total C1s
timeFrame: Baseline to Week 32
measure: Complement activity (classical pathway)
timeFrame: Baseline to Week 32
measure: Anti-RAY121 antibodies
timeFrame: Baseline to Week 32
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California-Irvine
state: California
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Lake Success
country: United States
facility: Northwell Health, LLC PRIME
state: New York
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania, Perelman Center for Advanced Medicine
state: Pennsylvania
city: Amarillo
country: United States
facility: Amarillo Center for Clinical Research
state: Texas
city: Houston
country: United States
facility: Nerve and Muscle Center of Texas
state: Texas
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Campbelltown Public Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Vienna
country: Austria
facility: AKH - Medizinische Universitaet Wien, Abteilung fuer Klinische Pharmakologie
city: Sofia
country: Bulgaria
facility: Diagnostic Consultation Center CONVEX EOOD
state: Sofia City Province
city: Sofia
country: Bulgaria
facility: "SHATHD" EAD Sofia
state: Sofia City Province
city: Stara Zagora
country: Bulgaria
facility: UMHAT "Prof. Dr. St. Kirkovich", AD
state: Stara Zagora Province
city: Edmonton
country: Canada
facility: University of Alberta Hospital - Department of Anesthesiology and Pain Medicine
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital - Dermatology
state: Alberta
city: Montreal
country: Canada
facility: The Royal Institution for the Advancement of Learning/McGill University
state: Quebec
city: Rimouski
country: Canada
facility: Centre de Rhumatologie de l'Est du Quebec
state: Quebec
city: Sherbrooke
country: Canada
facility: DIEX Recherche Sherbrooke Inc.
state: Quebec
city: Zagreb
country: Croatia
facility: Clinical Hospital Center "Sestre Milosrdnice"
state: City Of Zagreb
city: Zagreb
country: Croatia
facility: University hospital centre Zagreb
state: City Of Zagreb
city: Rijeka
country: Croatia
facility: Specialty Hospital Medico
state: Primorje-Gorski Kotar County
city: Prague
country: Czechia
facility: Sanatorium Profesora Arenbergera
state: City Of Prague
city: Montpellier
country: France
facility: Hopital Lapeyronie,Service d'Immuno Rhumatologie
state: Occitanie
city: Paris
country: France
facility: AP-HP Hôpital Universitaire Pitié Salpêtrière
state: Île-de-France
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
state: Baden-Württemberg
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen
state: Bavaria
city: Sachsen
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden, Klinik und Poliklinik f. Dermatologie
state: Bundesländer
city: Göttingen
country: Germany
facility: Universitaetsmedizin Goettingen
state: Göttingen District
city: Luebeck
country: Germany
facility: Universitaetsklinikum Schleswig Holstein - Campus Luebeck, Klinik f Dermatologie, Allergologie u Venerologie
state: Schleswig-Holstein
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
state: Csongrád-Csanád County
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Meldola
country: Italy
facility: IRCCS Istituto Scientifico Romagnolo Per Lo Studio Dei Tumori "Dino Amadori" - IRST
state: Forlì-Cesena Province
city: Milano
country: Italy
facility: Istituto Clinico Humanitas
state: Milan Province
city: Torino
country: Italy
facility: Ospedale San Giovanni Bosco
state: Turin Province
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Osakasayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Hamamatsu
country: Japan
facility: Hamamatsu University Hospital
state: Shizuoka
city: Kodaira
country: Japan
facility: National Center of Neurology and Psychiatry
state: Tokyo
city: Ota-ku
country: Japan
facility: Toho University Omori Medical Center
state: Tokyo
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Groningen
country: Netherlands
facility: University Medical Centre Groningen UMCG
state: Groningen Province
city: Utrecht
country: Netherlands
facility: UMC Utrecht
state: Utrecht Province
city: Kristiansand
country: Norway
facility: Sorlandet sykehus Kristiansand
state: Agder County
city: Stavanger
country: Norway
facility: Stavanger Universitetssjukehus
state: Rogaland County
city: Warszawa
country: Poland
facility: Institute Reumatologii I'm. Eleonory Reicher
state: Masovian Voivodeship
city: Braga
country: Portugal
facility: Centro Clinico Academico Braga
state: Braga District
city: Vila Nova De Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.
state: Porto District
city: Bucharest
country: Romania
facility: Centrul Medical Monza SRL
state: Bucharest Municipality
city: Cluj-Napoca
country: Romania
facility: Oncology Institute Prof. Dr. Ion Chiricuta I.O.C.N.
state: Cluj County
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Community Of Madrid & Navarre
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal, Servicio de Reumatologia
state: Community Of Madrid
city: Madrid
country: Spain
facility: Hospital Universitario 12 de October
state: Community Of Madrid
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron, Internal Medicine Dept.
state: Province Of Barcelona And Catalonia
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
state: Province Of Córdoba
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
state: Province Of Seville
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
state: Valencian Community
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taichung Veterans General Hospital
city: Ankara
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital
state: Ankara Province
city: Istanbul
country: Turkey
facility: Istanbul University Istanbul Medical Faculty
state: Istanbul Province
Study officials:
affiliation: clinical-trials@chugai-pharm.co.jp
name: Sponsor Chugai Pharmaceutical Co.Ltd
role: STUDY_DIRECTOR
References: