Trial reportRheumatology (Oxford, England)2016
Safety and patient response as indicated by biomarker changes to binding immunoglobulin protein in the phase I/IIA RAGULA clinical trial in rheumatoid arthritis.
Trial report in Rheumatology (Oxford, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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, 45 citations in OpenAlex.
- The Biologic IRL201805 Alters Immune Tolerance Leading to Prolonged Pharmacodynamics and Efficacy in Rheumatoid Arthritis Patients.International journal of molecular sciences · 2024Trial
- GALNT1 drives aggressive phenotypes of rheumatoid synoviocytes via NEK9 O-glycosylation.JCI insight · 2026Article
- Development of an efficient expression system for human chaperone BiP in Pichia pastoris: production optimization and functional validation.Microbial cell factories · 2025Article
- The Differential Expressions and Associations of Intracellular and Extracellular GRP78/Bip with Disease Activity and Progression in Rheumatoid Arthritis.Bioengineering (Basel, Switzerland) · 2025Article
- Citrullinated peptides as drug candidates for rheumatoid arthritis.Frontiers in immunology · 2025Review
- Introducing Molecular Chaperones into the Causality and Prospective Management of Autoimmune Hepatitis.Digestive diseases and sciences · 2023Review
- The therapeutic mavericks: Potent immunomodulating chaperones capable of treating human diseases.Journal of cellular and molecular medicine · 2023Review
- A peptide derived from HSP60 reduces proinflammatory cytokines and soluble mediators: a therapeutic approach to inflammation.Frontiers in immunology · 2023Review
- ER-stress-induced secretion of circulating glucose-regulated protein 78kDa (GRP78) ameliorates pulmonary artery smooth muscle cell remodelling.Cell stress & chaperones · 2022Article
- Heat Shock Proteins Alterations in Rheumatoid Arthritis.International journal of molecular sciences · 2022Review
- Proteomics based markers of clinical pain severity in juvenile idiopathic arthritis.Pediatric rheumatology online journal · 2022Article
- Endoplasmic reticulum stress associates with the development of intervertebral disc degeneration.Frontiers in endocrinology · 2022Review
- Regulation of neuroimmune processes by damage- and resolution-associated molecular patterns.Neural regeneration research · 2021Review
- Therapeutic Implications of Targeting Heat Shock Protein 70 by Immunization or Antibodies in Experimental Skin Inflammation.Frontiers in immunology · 2021Article
- Endoplasmic Reticulum Stress: An Emerging Therapeutic Target for Intervertebral Disc Degeneration.Frontiers in cell and developmental biology · 2021Review
- Heat Shock Protein 70 as a Double Agent Acting Inside and Outside the Cell: Insights into Autoimmunity.International journal of molecular sciences · 2020Review
- Vaccination against autoimmune diseases moves closer to the clinic.Human vaccines & immunotherapeutics · 2020Review
- Binding Immunoglobulin Protein (BIP) Inhibits TNF-α-Induced Osteoclast Differentiation and Systemic Bone Loss in an Erosive Arthritis Model.ACR open rheumatology · 2019Article
- ATPase activity of human binding immunoglobulin protein (BiP) variants is enhanced by signal sequence and physiological concentrations of MnFEBS open bio · 2019Article
- Heat shock proteins in the therapy of autoimmune diseases: too simple to be true?Cell stress & chaperones · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesBinding immunoglobulin protein (BiP) is a human endoplasmic reticulum-resident stress protein. In pre-clinical studies it has anti-inflammatory properties due to the induction of regulatory cells. This randomized placebo-controlled, dose ascending double blind phase I/IIA trial of BiP in patients with active RA, who had failed accepted therapies, had the primary objective of safety. Potential efficacy was measured by DAS28-ESR and changes in biomarkers.
methodsTwenty-four patients with active RA who had failed one or more DMARDs were sequentially assigned to three groups each of eight patients randomly allocated to receive placebo (two patients) or BiP (six patients), 1, 5 or 15 mg. Patients received a single i.v. infusion over 1 h and were observed as inpatients overnight. A 12-week follow-up for clinical, rheumatological and laboratory assessments for safety, efficacy (DAS28-ESR) and biomarker analysis was performed.
resultsNo infusion reactions or serious adverse drug reactions were noted. Adverse events were evenly distributed between placebo and BiP groups with no BiP-related toxicities. Haematological, renal and metabolic parameters showed no drug-related toxicities. Remission was only achieved by patients in the 5 and 15 mg groups, and not patients who received placebo or 1 mg BiP. Good DAS28-ESR responses were achieved in all treatment groups. The BiP responding patients showed significantly lower serum concentrations of CRP, 2 weeks post-infusion compared with pre-infusion levels, and of VEGF and IL-8 from the placebo group.
conclusionBiP (⩽15 mg) is safe in patients with active RA. Some patients had clinical and biological improvements in RA activity. BiP merits further study.
trial registrationISRCTN registry, http://isrctn.com, ISRCTN22288225 and EudraCT, https://eudract.ema.europa.eu, 2011-005831-19.
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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.