ArticleVaccine2008
Open-label, dose escalation phase I study in healthy volunteers to evaluate the safety and pharmacokinetics of a human monoclonal antibody to Clostridium difficile toxin A.
Article in Vaccine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Determination of the starting dose in the first-in-human clinical trials with monoclonal antibodies: a systematic review of papers published between 1990 and 2013.Drug design, development and therapy · 2016Pooled it
- Immunization Strategies Against Clostridioides difficile.Advances in experimental medicine and biology · 2024Review
- Application of recombinant antibodies for treatment ofFrontiers in immunology · 2022Review
- Predicting monoclonal antibody pharmacokinetics following subcutaneous administration via whole-body physiologically-based modeling.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- A generic whole body physiologically based pharmacokinetic model for therapeutic proteins in PK-Sim.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- Bezlotoxumab: an emerging monoclonal antibody therapy for prevention of recurrentBiologics : targets & therapy · 2018Review
- Application of Antibody-Mediated Therapy for Treatment and Prevention ofFrontiers in microbiology · 2018Review
- A Tetraspecific VHH-Based Neutralizing Antibody Modifies Disease Outcome in Three Animal Models of Clostridium difficile Infection.Clinical and vaccine immunology : CVI · 2016Article
- Physiologically-based pharmacokinetic modeling to predict the clinical pharmacokinetics of monoclonal antibodies.Journal of pharmacokinetics and pharmacodynamics · 2016Article
- An update on antibody-based immunotherapies for Clostridium difficile infection.Clinical and experimental gastroenterology · 2016Review
- Colonization Resistance of the Gut Microbiota against Clostridium difficile.Antibiotics (Basel, Switzerland) · 2015Review
- The roles of host and pathogen factors and the innate immune response in the pathogenesis of Clostridium difficile infection.Molecular immunology · 2015Review
- Biochemical and Immunological Characterization of Truncated Fragments of the Receptor-Binding Domains of C. difficile Toxin A.PloS one · 2015Article
- Antibodies for treatment of Clostridium difficile infection.Clinical and vaccine immunology : CVI · 2014Review
- Article
- Clostridium difficile infection in the twenty-first century.Emerging microbes & infections · 2013Review
- Giving monoclonal antibodies to healthy volunteers in phase 1 trials: is it safe?British journal of clinical pharmacology · 2013Review
- Pseudomembranous colitis due to Clostridium difficile as a cause of perineal necrotising fasciitis.BMJ case reports · 2013Article
- Antibody against TcdB, but not TcdA, prevents development of gastrointestinal and systemic Clostridium difficile disease.The Journal of infectious diseases · 2013Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundRecent data suggest that Clostridium difficile-associated diarrhea is becoming more severe and difficult to treat. Antibody responses to C. difficile toxin A are protective against symptomatic disease and recurrence. We examined the safety and pharmacokinetics (pk) of a novel neutralizing human monoclonal antibody against C. difficile toxin A (CDA1) in healthy adults.
methodsFive cohorts with 6 subjects each received a single intravenous infusion of CDA1 at escalating doses of 0.3, 1, 5, 10, and 20 mg/kg. Safety evaluations took place on days 1, 2, 3, 7, 14, 28, and 56 post-infusion. Samples for pk analysis were obtained before and after infusion, and at each safety evaluation. Serum CDA1 antibody concentrations and human anti-human antibody (HAHA) titers were measured with enzyme-linked immunosorbent assays. A noncompartmental model was used for pk analysis.
resultsThirty subjects were enrolled. The median age was 27.5 yrs. There were no serious adverse events (AE) related to CDA1. Twenty-one of the 48 reported non-serious adverse events were possibly related to CDA1, and included transient blood pressure changes requiring no treatment, nasal congestion, headache, abdominal cramps, nausea, and self-limited diarrhea. Serum CDA1 concentrations increased with escalating doses: mean C(max) ranged from 6.82 microg/ml for the 0.3 mg/kg cohort to 511 microg/ml for the 20 mg/kg cohort. The geometric mean values of the half-life of CDA1 ranged between 25.3 and 31.8 days, and the volume of distribution approximated serum. No subject formed detectable HAHA titers.
conclusionAdministration of CDA1 as a single intravenous infusion was safe and well tolerated. C(max) increased proportionally with increasing doses. A randomized study of CDA1 in patients with C. difficile associated diarrhea is underway.
Indexed as
Identifiers
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.