ORPHA:56425
Cold agglutinin disease
Also known as: CAD · CAS · Chronic cold agglutinin disease · Cold agglutinin syndrome
Publications
1,921
88.2th percentile
Trials
16
Interventional, condition-specific
Researchers
1,007
Distinct authors in sample
Gene link
—
Readiness
3/6
Stages with a signal
Clinical definition (Orphanet)
Cold agglutinin disease is a type of autoimmune hemolytic anemia defined by the presence of cold autoantibodies (autoantibodies which are active at temperatures below 30°C).
How rare: 1-9 / 1 000 000 — roughly one to nine people per million. In a city the size of Kolkata, perhaps a few dozen.
Cross-references
Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.
- MONDO:0018922
- UMLS:C1264008
Additional Mondo synonyms (2)
chronic cold agglutinin disease · cold agglutinin syndrome
Research stages
Trial readiness signals
Where this condition sits on an open-data research pipeline — not how close a treatment is, and not medical advice. Empty stages often mean “not in these databases under this Mondo ID,” not “impossible.”
3/6 stages with a signal
An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.
- Gene identifiedNot found
No GenCC disease–gene assertion in this build
- LiteraturePresent
1,921 matched papers (1,208 in last 10 years) Source
- Phenotype characterisedPresent
14 HPO annotations (e.g. Back pain; Splenomegaly; Hepatomegaly) Source
- Animal modelNot found
No Alliance genotype “model of” associations via Monarch for these Mondo IDs
- Orphan designationNot found
No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source
- Interventional trialPresent
16 matched on ClinicalTrials.gov (1 recruiting in sample)
Biology
Genes and phenotypes
Gene–disease validity from GenCC, plus phenotypes and animal models joined from Monarch Initiative via Mondo ID — not a clinical diagnosis aid.
Do we know what causes it?
Not yet — the cause hasn't been pinned down in GenCC.
No strong gene–disease assertion joined for this Orphanet entity.
Phenotypes (Monarch / HPO)
14
Associated phenotypes · MONDO:0018922
- Back pain
- Splenomegaly
- Hepatomegaly
- Autoimmunity
- Fatigue
Showing 5 of 14 — open Monarch for the full list.
Animal models (Monarch / Alliance)
None returned for this Mondo ID. Empty here is not proof that no model organism work exists under another name or gene.
Monarch fetch 2026-07-29
Therapies
Designations, candidates, and chemicals
FDA OOPD and EMA orphan designations, Open Targets clinical candidates, and CTD chemical associations via MyDisease.info. These never change the interventional-trial headline.
Orphan designation (FDA · EMA)
No designation matched this disease via UMLS or preferred name on the FDA OOPD mirror or EMA orphan register. Absence here is not proof that none exists under another wording.
Open Targets candidates
11
Drugs / clinical candidates · MONDO_0018922
- PEGCETACOPLAN·phase 3
- BENDAMUSTINE·phase 2
- BORTEZOMIB·phase 2
- ECULIZUMAB·phase 2
- FLUDARABINE·phase 2
- RITUXIMAB·phase 2
- ZANUBRUTINIB·phase 2
- RILIPRUBART·phase 1
- ANTITHROMBIN GAMMA·approval
- POVETACICEPT·phase 1 2
- SUTIMLIMAB·approval
CTD chemicals (MyDisease.info)
No CTD chemical associations returned for this Mondo ID.
Literature
Is anyone studying this?
1,921
1,921 papers have been published on this condition. That is a real research literature — still far smaller than common diseases (breast cancer: over 700,000 papers). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.
1,921 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 59 (publications denominator n=3967).
1,208 in the last 10 years · medium confidence · 88.2th percentile (publications denominator)
Phrase hits: 1,921 · MeSH hits: 0
Who's working on it?
1,007
Distinct author names in 200 sampled papers — named people below.
Who's working on it?
People publishing on this condition (sampled Europe PMC records). Affiliation is the most recent found in that sample.
- 01Fattizzo B16 papers · 2026
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Papers in Europe PMC - 02Barcellini W14 papers · 2026
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Papers in Europe PMC - 03Berentsen S10 papers · 2026
Department of Research and Innovation, Haugesund Hospital, Haugesund, Norway.
Papers in Europe PMC - 04Röth A7 papers · 2026
Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Papers in Europe PMC - 05Vos JMI7 papers · 2026
Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Papers in Europe PMC - 06Michel M6 papers · 2026
Henri-Mondor University Hospital, Assistance Publique-Hôpitaux de Paris, UPEC, Créteil, France.
Papers in Europe PMC - 07Broome CM5 papers · 2026
Division of Hematology, MedStar Georgetown University Hospital, Washington, DC, USA.
Papers in Europe PMC - 08D'Sa S4 papers · 2024
UCLH Centre for Waldenström's Macroglobulinemia and Related Conditions, University College London Hospitals NHS Foundation Trust, London, UK.
Papers in Europe PMC - 09Miyakawa Y4 papers · 2026
Department of General Internal Medicine, Saitama Medical University Hospital, Saitama, Japan.
Papers in Europe PMC - 10
Clinical research
Is a treatment being tested?
16
interventional trials for this specific condition
16 interventional trials matched this specific condition name; 1 currently recruiting in our sample.
Data as of 11 September 2026
16 interventional trials — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 94.2th percentile).
medium confidence · 94.2th percentile (trials denominator)
Recruiting interventional trials
From the matched ClinicalTrials.gov set
16 interventional trials matched after quoted-phrase search and title/condition post-filter.
- NCT05318534·RECRUITING·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
Not reviewed·Conditions: First in Man Study to Evaluate Initial Safety·Matched via name phrase
Observational and natural-history studies
3 observational studies match this condition. These do not test a treatment and are not counted in the interventional-trial headline, but they are genuine research: natural-history work often defines the endpoints needed for a future rare-disease trial, and families may be able to enroll.
Recruiting or not-yet-recruiting
- NCT05931718·RECRUITING·Prospective Evaluation of Diagnosis and Treatment of Patients With Autoimmune Cytopenias Including Autoimmune Hemolytic Anemia, Immune Thrombocytopenia, and Chronic Idiopathic/Autoimmune Neutropenia
Not reviewed·Conditions: Autoimmune Hemolytic Anemia · Immune Thrombocytopenia · Chronic Idiopathic Neutropenia · Autoimmune Neutropenia·Matched via name phrase
Other registries (secondary)
Broader net from EU CTIS, ISRCTN, and ICTRP when available — deduped against ClinicalTrials.gov IDs already counted above. Dual-model LLM relevance gates what we keep. These rows are not added to the interventional headline.
raw 7 · after dedupe 7 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 7 · dropped 0 · fetched 2026-07-29
Source notes: ictrp: Error: ICTRP public search unavailable (WHO portal is SPA-only; SOAP needs partnership). Tried: https://apps.who.int/tri
No secondary-registry studies passed dual-model relevance for this condition name (after dedupe).
Uncertain / not reviewed (7)
- ctis·2023-505746-25-00·Expired·HOVON 169 CAD: Phase II trial of Zanubrutinib in primary Cold Agglutinin Disease. CaZa study
skipped — LLM skipped (--skip-llm)
- ctis·2023-507067-19-00·Cancelled·Open-Label Study to Assess the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Povetacicept in Subjects with Autoimmune Cytopenias (RUBY-4)
skipped — LLM skipped (--skip-llm)
- ctis·2023-510210-68-00·Cancelled·An open-label, long-term, safety and tolerability study of SAR445088 in participants with cold agglutinin disease previously treated with SAR445088 or never treated with SAR445088
skipped — LLM skipped (--skip-llm)
- ctis·2023-507017-10-00·Cancelled·A Phase 1b, Open-Label, Single-Arm Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Effect of ANX1502 in Participants with Primary Cold Agglutinin Disease
skipped — LLM skipped (--skip-llm)
- isrctn·ISRCTN13110963·No longer recruiting·A phase 3 study of obexelimab in patients with warm autoimmune hemolytic anemia
skipped — LLM skipped (--skip-llm)
- isrctn·ISRCTN14903256·No longer recruiting·Study of the efficacy and safety of parsaclisib in participants with primary warm autoimmune hemolytic anemia
skipped — LLM skipped (--skip-llm)
- isrctn·ISRCTN00283877·No longer recruiting·A multicentre study to determine the efficacy and patient acceptability of scalp cooling in the prevention of docetaxel-induced hair loss
skipped — LLM skipped (--skip-llm)
Where to find support
Condition-specific patient organisations, when Orphanet lists them, are on the disease’s Orphanet page. We also link umbrella groups that support undiagnosed and ultra-rare families.
Orphanet entry for Cold agglutinin disease — check Associations / patient organisations on that page.
India — NPRD
Last verified 2026-07-26This ORPHAcode is not on our curated NPRD list (direct or Mondo-parent match). That does not decide clinical eligibility; families in India should ask a notified Centre of Excellence about current coverage.
Hand-curated for this project. ORPHAcode mappings are best-effort and may be incomplete or imprecise for umbrella categories. Parent (Mondo) matches mean the policy lists a broader category — confirm eligibility with a Centre of Excellence. Financial entitlements summarised from public policy statements and may change. This is not official government guidance.
How we counted this
Europe PMC query (preferred label + any corrected label + Orphanet and Mondo exact synonyms, stoplisted; unioned with resolved MeSH labels when available). UMLS / OMIM / NCIT cross-references are stored on the overview but are not added to the query string.
"Cold agglutinin disease" OR "Chronic cold agglutinin disease" OR "Cold agglutinin syndrome"
ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"Cold agglutinin disease" OR "Chronic cold agglutinin disease" OR "Cold agglutinin syndrome"
Interventional trials matched via: phrase (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).
Study-type breakdown: 16 interventional · 3 observational · 0 expanded access. Only interventional studies enter the trial headline.
Query health: ok — strategies attempted: phrase; with hits: phrase
Run this search on ClinicalTrials.gov
Synonyms dropped by stoplist: CAD; CAS
Confidence reasoning
- Preferred label is multi-word and distinctive
- 2 synonym(s) dropped by stoplist (may under-count)
- No label/synonym collisions with other diseases in this corpus
Ingested 2026-07-27T00:59:14.618Z