Safety and patient response as indicated by biomarker changes to binding immunoglobulin protein in the phase I/IIA RAGULA clinical trial in rheumatoid arthritis

Autor: Alexandra Vincent, A T Prevost, Joana C. Vasconcelos, Christopher Hall, Timothy Mant, Toby Garrood, Valerie Corrigall, Elizabeth Allen, Khaldoun Chaabo, Bruce Kirkham, Gabriel S. Panayi
Rok vydání: 2016
Předmět:
Adult
Male
Vascular Endothelial Growth Factor A
0301 basic medicine
medicine.medical_specialty
Adolescent
genetic structures
Placebo
Gastroenterology
Arthritis
Rheumatoid
Young Adult
03 medical and health sciences
0302 clinical medicine
Double-Blind Method
Rheumatology
Internal medicine
medicine
Humans
Pharmacology (medical)
Interleukin 8
skin and connective tissue diseases
Infusions
Intravenous
Adverse effect
Aged
030203 arthritis & rheumatology
Biological Products
Lymphokines
biology
business.industry
Interleukin-8
Remission Induction
Middle Aged
Clinical Science
medicine.disease
Recombinant Proteins
Clinical trial
Treatment Outcome
030104 developmental biology
Antirheumatic Agents
Rheumatoid arthritis
Immunology
biology.protein
Biomarker (medicine)
Female
Binding immunoglobulin protein
Antibody
business
Biomarkers
Zdroj: Rheumatology. 55:1993-2000
ISSN: 1462-0332
1462-0324
Popis: Objectives Binding 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. Methods Twenty-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. Results No 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. Conclusion BiP (⩽15 mg) is safe in patients with active RA. Some patients had clinical and biological improvements in RA activity. BiP merits further study. Trial registration ISRCTN registry, http://isrctn.com, ISRCTN22288225 and EudraCT, https://eudract.ema.europa.eu, 2011-005831-19.
Databáze: OpenAIRE
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