Trial reportPloS one2016
Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study.
Trial report in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 73 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 147 citations in OpenAlex.
- Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.Pharmacological reviews · 2021Pooled it
- Safety and Efficacy of Avacopan in Patients with Complement 3 Glomerulopathy: Randomized, Double-Blind Clinical Trial.Journal of the American Society of Nephrology : JASN · 2025Trial
- A phase I thorough QT/QTc study evaluating therapeutic and supratherapeutic doses of avacopan in healthy participants.Clinical and translational science · 2024Trial
- Pre-existing antibody-mediated adverse effects prevent the clinical development of a bacterial anti-inflammatory protein.Disease models & mechanisms · 2020Trial
- Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis.Journal of the American Society of Nephrology : JASN · 2017Trial
- Early experience of avacopan for ANCA-associated vasculitis in an Australian paediatric population: a case series.EULAR rheumatology open · 2026Article
- Innovative Clinical Pharmacology, Modeling, and Simulation Strategies for Accelerating Rare Disease Drug Development.Journal of clinical pharmacology · 2026Review
- A Phase 1 Study Evaluating the Pharmacokinetics and Safety of Avacopan in Participants with End-Stage Kidney Disease on Hemodialysis.Journal of clinical pharmacology · 2026Article
- C5aR1 and cGAS/STING and their possible involvement in radiosensitivity of colorectal cancer.iScience · 2026Review
- Predictors of glucocorticoid-free clinical remission in patients with newly diagnosed microscopic polyangiitis and granulomatosis with polyangiitis: a retrospective cohort study using a nationwide registry in Japan (J-CANVAS).Arthritis research & therapy · 2026Article
- Targeting the complement system in ANCA-associated vasculitis management.Rheumatology (Oxford, England) · 2026Review
- IgA Nephropathy: An Overview of the Clinical Trials.Kidney medicine · 2025Review
- UPR-induced intracellular C5aR1 promotes adaptation to the hypoxic tumour microenvironment.Cell death & disease · 2025Article
- Safety of Avacopan for the Treatment of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Combined Data From Three Clinical Trials.ACR open rheumatology · 2025Article
- Targeted Complement Treatments in Glomerulopathies: A Comprehensive Review.Journal of clinical medicine · 2025Review
- Evaluating Avacopan in the Treatment of ANCA-Associated Vasculitis: Design, Development and Positioning of Therapy.Drug design, development and therapy · 2025Review
- Complement-targeted therapeutics: Are we there yet, or just getting started?European journal of immunology · 2024Review
- Treatment of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Diffuse Alveolar Hemorrhage With Avacopan.ACR open rheumatology · 2024Article
- A case of rapid avacopan-induced liver injury in pediatric granulomatosis with polyangiitis.Pediatric nephrology (Berlin, Germany) · 2024Article
- Avacopan for antineutrophil cytoplasmic antibody-associated vasculitis.Australian prescriber · 2024Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan), an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood. A transgenic human C5aR knock-in mouse model allowed comparison of the in vitro and in vivo efficacy of the molecule. CCX168 effectively blocked migration in in vitro and ex vivo chemotaxis assays, and it blocked the C5a-mediated neutrophil vascular endothelial margination. CCX168 was effective in migration and neutrophil margination assays in cynomolgus monkeys. This thorough in vitro and preclinical characterization enabled progression of CCX168 into the clinic and testing of its safety, tolerability, pharmacokinetic, and pharmacodynamic profiles in a Phase 1 clinical trial in 48 healthy volunteers. CCX168 was shown to be well tolerated across a broad dose range (1 to 100 mg) and it showed dose-dependent pharmacokinetics. An oral dose of 30 mg CCX168 given twice daily blocked the C5a-induced upregulation of CD11b in circulating neutrophils by 94% or greater throughout the entire day, demonstrating essentially complete target coverage. This dose regimen is being tested in clinical trials in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Trial Registration ISRCTN registry with trial ID ISRCTN13564773.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.