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)

Overview

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).

Interventions

• Drug RAY121
  Injection

Primary outcome measures

• Adverse events (AEs) [Time frame: Baseline to Week 32]

Secondary outcome measures (8)

• RAY121 concentration [Time frame: Baseline to Week 32]
• AUCτ [Time frame: Baseline to Week 32]
• Cmax [Time frame: Baseline to Week 32]
• Cmin [Time frame: Baseline to Week 32]
• Active C1s [Time frame: Baseline to Week 32]
• Total C1s [Time frame: Baseline to Week 32]
• Complement activity (classical pathway) [Time frame: Baseline to Week 32]
• Anti-RAY121 antibodies [Time frame: Baseline to Week 32]

Eligibility criteria

• Signed informed consent form
• Age ≥ 18 and ≤ 85 at the time of signing informed consent form with Karnofsky score ≥ 60 % at screening
• Ability to comply with the study protocol
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
• 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 LA test
• Persistently positive aCL IgG isotype
• Persistently positive aβ2GPI IgG isotype
• Clinical criteria

• Livedoid vasculopathy and presence of skin ulcer
• Acute/chronic aPL nephropathy
• BP cohort:

1\) Predominant cutaneous lesions 2) Diagnosis with BP with following assessments positive:

• Positive direct immunofluorescence, and either
• Positive indirect immunofluorescence, or
• Positive serology on ELISA for BP180 autoantibody 3) BPDAI score >= 20 4) Weekly average of daily Peak Pruritus NRS >=4 5) Accept to take photograph of bullous lesions

8\. BS cohort:

• Diagnosed with BS
• Oral ulcers that occurred at least 3 times in the previous 12 month period
• Have at least 2 oral ulcers over the 4 weeks prior to screening
• Have at least 2 oral ulcers at Week 0
• Have prior treatment with at least 1 non-biologic BS therapy
• Patients who need systemic therapy as whose oral or mucocutaneous ulcers cannot be adequately controlled by topical therapy

9\. DM cohort:

• Diagnosed with definite or probable inflammatory myopathies and categorized as DM
• Patients with inadequate response to corticosteroids and/or immune-suppressants or intolerance to DM therapies
• MMT-8 score < 142, with at least one abnormality in the following Core Set Measures:

• PtGA-VAS >= 2 cm
• PhGA-VAS >= 2 cm
• Global extra-muscular activity >= 2 cm
• At least one muscle enzyme > 1.5 times ULN
• HAQ >= 0.25
• Moderate to severe DM defined as CDASI activity score > 14

10\. IMNM cohort:

• Clinically Diagnosed with IMNM as anti-HMGCR myopathy or anti-SRP myopathy
• CK > 1,000 U/L
• Patients who have an inadequate response to corticosteroids and/or immunesuppressants or intolerance to IMNM therapies
• MMT-8 score < 142

11\. ITP cohort:

• 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
• Lack of an sustained adequate platelet count response to a thrombopoietin receptor agonist and at least one other ITP treatment or a second TPO-RA
• 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

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

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Japan · 13 centers

• Hokkaido University Hospital — Sapporo
• Hyogo Prefectural Harima-Himeji General Medical Center — Himeji
• Tokai University Hospital — Isehara
• Tohoku University Hospital — Sendai
• Tohoku Medical and Pharmaceutical University Hospital — Sendai
• Kindai University Hospital — Sakai
• The University of Osaka Hospital — Suita
• Hamamatsu University Hospital — Hamamatsu
• … and 5 more centers

United States · 11 centers

• University of California-Irvine — Orange
• Johns Hopkins University — Baltimore
• Northwell Health, LLC PRIME — Lake Success
• Hospital for Special Surgery — New York
• Universtity of North Carolina at Chapel Hill — Chapel Hill
• Ohio State University — Columbus
• Oregon Health & Science University — Portland
• University of Pennsylvania, Perelman Center for Advanced Medicine — Philadelphia
• … and 3 more centers

Spain · 7 centers

• Clinica Universidad de Navarra — Pamplona
• Hospital Universitario Ramon y Cajal, Servicio de Reumatologia — Madrid
• Hospital Universitario 12 de October — Madrid
• Hospital Universitari Vall d'Hebron, Internal Medicine Dept. — Barcelona
• Hospital Universitario Reina Sofia — Córdoba
• Hospital Universitario Virgen del Rocio — Seville
• Hospital Universitari i Politecnic La Fe — Valencia

Germany · 6 centers

• Universitaetsklinikum Tuebingen — Tübingen
• Universitaetsklinikum Erlangen — Erlangen
• Immanuel Klinik Rudersdorf — Rüdersdorf
• Universitaetsklinikum Carl Gustav Carus TU Dresden, Klinik und Poliklinik f. Dermatologie — Sachsen
• Universitaetsmedizin Goettingen — Göttingen
• Universitaetsklinikum Schleswig Holstein - Campus Luebeck, Klinik f Dermatologie, Allergol — Lübeck

Australia · 5 centers

• Royal Prince Alfred Hospital — Camperdown
• Westmead Hospital — Sydney
• Campbelltown Public Hospital — Sydney
• The Alfred Hospital — Melbourne
• Box Hill Hospital — Melbourne

Canada · 5 centers

• University of Alberta Hospital - Department of Anesthesiology and Pain Medicine — Edmonton
• University of Alberta Hospital - Dermatology — Edmonton
• The Royal Institution for the Advancement of Learning/McGill University — Montreal
• Centre de Rhumatologie de l'Est du Quebec — Rimouski
• DIEX Recherche Sherbrooke Inc. — Sherbrooke

Bulgaria · 4 centers

• Diagnostic Consultation Center CONVEX EOOD — Sofia
• UMHAT Sv Ivan Rilski EAD — Sofia
• "SHATHD" EAD Sofia — Sofia
• UMHAT "Prof. Dr. St. Kirkovich", AD — Stara Zagora

Croatia · 3 centers

• Clinical Hospital Center "Sestre Milosrdnice" — Zagreb
• University hospital centre Zagreb — Zagreb
• Specialty Hospital Medico — Rijeka

Italy · 3 centers

• IRCCS Istituto Scientifico Romagnolo Per Lo Studio Dei Tumori "Dino Amadori" - IRST — Meldola
• Istituto Clinico Humanitas — Milan
• Ospedale San Giovanni Bosco — Torino

Norway · 3 centers

• Sorlandet sykehus Kristiansand — Kristiansand
• Stavanger Universitetssjukehus — Stavanger
• Sykehuset Ostfold Fredrikstad — Fredrikstad

France · 2 centers

• Hopital Lapeyronie,Service d'Immuno Rhumatologie — Montpellier
• AP-HP Hôpital Universitaire Pitié Salpêtrière — Paris

Hungary · 2 centers

• Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont — Szeged
• Semmelweis Egyetem — Budapest

Netherlands · 2 centers

• University Medical Centre Groningen UMCG — Groningen
• UMC Utrecht — Utrecht

Portugal · 2 centers

• Centro Clinico Academico Braga — Braga
• Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E. — Vila Nova de Gaia

Romania · 2 centers

• Centrul Medical Monza SRL — Bucharest
• Oncology Institute Prof. Dr. Ion Chiricuta I.O.C.N. — Cluj-Napoca

Taiwan · 2 centers

• National Taiwan University Hospital — Taipei
• Taichung Veterans General Hospital — Taipei

Turkey (Türkiye) · 2 centers

• Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital — Ankara
• Istanbul University Istanbul Medical Faculty — Istanbul

Austria · 1 center

• AKH - Medizinische Universitaet Wien, Abteilung fuer Klinische Pharmakologie — Vienna

Czechia · 1 center

• Sanatorium Profesora Arenbergera — Prague

Poland · 1 center

• Institute Reumatologii I'm. Eleonory Reicher — Warsaw

Identifiers

NCT: NCT06371417 · RAY902CT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗