{"doi":"10.1038/s43856-024-00575-y","title":"Safety and tolerability of the protein C activator AB002 in end-stage renal disease patients on hemodialysis: a randomized phase 2 trial","abstract":"BACKGROUND: The protein C system regulates blood coagulation, inflammation, and vascular integrity. AB002 is an injectable protein C activating enzyme under investigation to safely prevent and treat thrombosis. In preclinical models, AB002 is antithrombotic, cytoprotective, and anti-inflammatory. Since prophylactic use of heparin is contraindicated during hemodialysis in some end-stage renal disease (ESRD) patients, we propose using AB002 as a short-acting alternative to safely limit blood loss due to clotting in the dialysis circuit. METHODS: This phase 2, randomized, double-blind, placebo-controlled, single-dose study evaluates the safety and tolerability of AB002 administered into the hemodialysis line of ESRD patients during hemodialysis at one study center in the United States (ClinicalTrials.gov: NCT03963895). In this study, 36 patients were sequentially enrolled into two cohorts and randomized to AB002 or placebo in a 2:1 ratio. In cohort 1, patients received 1.5 µg/kg AB002 (n = 12) or placebo (n = 6); in cohort 2, patients received 3 µg/kg AB002 (n = 12) or placebo (n = 6). Patients underwent five heparin-free hemodialysis sessions over 10 days and were dosed with AB002 or placebo during session four. RESULTS: Here we show that AB002 is safe and well-tolerated in ESRD patients, with no treatment-related adverse events. Clinically relevant bleeding did not occur in any patient, and the time to hemostasis at the vascular access sites is not affected by AB002. CONCLUSIONS: As far as we are aware, this proof-of-concept study is the first clinical trial assessing the therapeutic potential of protein C activation. The results herein support additional investigation of AB002 to safely prevent and treat thrombosis in at-risk populations.","journal":"Communications Medicine","year":2024,"id":501592,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03963895"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":339126,"name":"Christina U. Lorentz","orcid":"0000-0002-6885-2352","position":1,"is_corresponding":false},{"id":443811,"name":"Brandon D. Markway","orcid":"0000-0001-8865-1649","position":2,"is_corresponding":false},{"id":356258,"name":"Michael Wallisch","orcid":"0000-0002-7133-795X","position":3,"is_corresponding":false},{"id":1350951,"name":"Thomas Marbury","orcid":"0000-0002-6416-3314","position":4,"is_corresponding":false},{"id":369910,"name":"Enrico Di","orcid":"0000-0003-2300-4891","position":5,"is_corresponding":false},{"id":339124,"name":"Joseph J. Shatzel","orcid":"0000-0001-9396-5976","position":6,"is_corresponding":false},{"id":339129,"name":"András Gruber","orcid":"0000-0001-6212-2247","position":7,"is_corresponding":false},{"id":339127,"name":"Erik I. Tucker","orcid":"0000-0003-0532-113X","position":8,"is_corresponding":false},{"id":443810,"name":"Norah G. Verbout","orcid":"0000-0002-8170-9331","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T02:10:15.999370Z","pmid":"39060370","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}