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Testing RAY121 for various immunological diseases

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

Phase 1 Interventional Chugai Pharmaceutical · NCT06371417

This study is testing a new drug called RAY121 to see if it can safely help people with different immune system diseases like antiphospholipid syndrome and dermatomyositis.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment144 (estimated)
Ages18 Years to 85 Years
SexAll
SponsorChugai Pharmaceutical Industry-sponsored
Locations69 sites (Orange, California and 68 other locations)
Trial IDNCT06371417 on ClinicalTrials.gov

What this trial studies

This Phase 1b basket trial evaluates the safety and effectiveness of RAY121, an inhibitor of the classical complement pathway, in patients with several immunological diseases including antiphospholipid syndrome, bullous pemphigoid, Behçet's syndrome, dermatomyositis, and immune-mediated necrotizing myopathy. The study will assess pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy after multiple doses of the drug. Participants will be monitored for tolerability and safety throughout the trial.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 75 with established primary antiphospholipid syndrome or other specified immunological diseases.

Not a fit: Patients with conditions not included in the study or those outside the specified age range may not benefit from this trial.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from these challenging immunological conditions.

How similar studies have performed: Other studies targeting the classical complement pathway have shown promise, suggesting potential for success in this novel approach.

Eligibility criteria

Show full 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

Where this trial is running

Orange, California and 68 other locations

+19 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Antiphospholipid SyndromeBullous PemphigoidBehçet's SyndromeDermatomyositisImmune-mediated Necrotizing MyopathyImmune Thrombocytopenia
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.