RecruitingPhase 1NCT07083960
Blood
Cold Agglutinin Disease
Also known as cold hemagglutinin disease, CAD, cold antibody AIHA
Cold agglutinin disease is a distinct subtype of autoimmune hemolytic anemia characterized by IgM autoantibodies (cold agglutinins) that bind to I or i antigens on red blood cell surfaces at cold temperatures, leading to complement C3 depos
ORPHA:56425 ↗Prevalence Approximately 1 per millionOnset Older adults; median age of diagnosis approximately 67-72 yearsAcquired (primary or secondary to lymphoproliferative disorder)
4
studies recruiting now
as of 7 Sept 2026
23
studies registered in total
as of 7 Sept 2026
5
countries with a recruiting site
as of 7 Sept 2026
24 Jul 2025
most recent study posted
among recruiting studies
Recruiting trials
RecruitingPhase 1NCT05318534
Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Male and Female Subjects and Safety, Tolerability, Pharmacokinetics, and Pilot Efficacy Biomarkers in Subjects With Cold Agglutinin Disease
RecruitingNCT07019038
National Longitudinal Cohort of Hematological Diseases- Autoimmune Hemolytic Anemia
RecruitingNCT05931718
Prospective Evaluation of Diagnosis and Treatment of Patients With Autoimmune Cytopenias Including Autoimmune Hemolytic Anemia, Immune Thrombocytopenia, and Chronic Idiopathic/Autoimmune Neutropenia
Showing the 4 most recently updated recruiting studies, as recorded 7 Sept 2026. Live status on each study page.
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Countries with at least one recruiting site among the studies above, 7 Sept 2026. Tap a country to search trials there.
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About Cold Agglutinin Disease
Cold agglutinin disease is a distinct subtype of autoimmune hemolytic anemia characterized by IgM autoantibodies (cold agglutinins) that bind to I or i antigens on red blood cell surfaces at cold temperatures, leading to complement C3 deposition and subsequent C1-mediated intravascular hemolysis and extravascular hemolysis in the liver. Primary CAD is a clonal lymphoproliferative disorder of the bone marrow producing monoclonal IgM cold agglutinins, while secondary CAD is associated with infections (Mycoplasma pneumoniae, EBV) or lymphoma. Cold temperatures trigger or exacerbate hemolysis, acrocyanosis, and Raynaud-like phenomena, significantly impairing quality of life.
Common clinical features
Chronic hemolytic anemia worsened by cold exposureAcrocyanosis and Raynaud phenomenon in cold temperaturesFatigue and pallor from chronic anemiaHemoglobinuria in cold-triggered acute hemolytic episodesElevated cold agglutinin titer (typically above 1:64 at 4 degrees Celsius)C3-positive but IgG-negative direct antiglobulin testJaundice and elevated LDH from ongoing hemolysisLivedo reticularis
From Orphanet’s phenotype annotations (CC BY 4.0). Not a complete list.
Treatments being studied
2 approved treatments and 4 in clinical development, from Open Targets (CC BY 4.0). Not medical advice.
Approved: Antithrombin GammaApproved: Sutimlimab (Enjaymo)
Phase 3Pegcetacoplan (Aspaveli)
Phase 2Eculizumab (Bekemv)
Phase 1/2Povetacicept (Variant tnf receptor domain)
Phase 1Riliprubart
Before you apply
Things trial teams commonly ask about for Cold Agglutinin Disease. Not eligibility rules; those are set by each study.
- Cold agglutinin titer (measured at 4 degrees Celsius with monospecific anti-IgM serum) above 1:64 and DAT positive for C3d only (IgG negative) are diagnostic requirements for most CAD trials; bring laboratory documentation from a reference laboratory.
- Complement pathway inhibitor trials (targeting C1s, C1q, or C3) are the most active therapeutic area in CAD; prior rituximab response and current hemoglobin level and transfusion frequency determine eligibility.
- Bone marrow biopsy documenting underlying clonal lymphoproliferative disorder distinguishes primary CAD from secondary CAD and affects trial eligibility; bring biopsy and immunohistochemistry results.
Related conditions
Information, not medical advice. Trial listings are shown as recorded on ClinicalTrials.gov; whether any study is right for you is a decision for you and your clinicians, and eligibility is decided by each research team. Disease information from Orphanet (CC BY 4.0).