Trial reportAnnals of the rheumatic diseases2019
Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker variables in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study.
Trial report in Annals of the rheumatic diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01751776 (A Randomised, Double-blind, Placebo-controlled Trial for Establishing Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Efficacy of Multiple Subcutaneous Doses of BI 655064 in Healthy Volunteers and in Rheumatoid Arthritis Patients With Prior Inadequate Response to Methotrexate Therapy), which is not on this map. Cited by 39 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.
A Randomised, Double-blind, Placebo-controlled Trial for Establishing Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Efficacy of Multiple Subcutaneous Doses of BI 655064 in Healthy Volunteers and in Rheumatoid Arthritis Patients With Prior Inadequate Response to Methotrexate Therapy
Who cites it
39 citing papers in PubMed, 60 citations in OpenAlex.
- Safety, pharmacokinetics and pharmacodynamics of BI 655064 in phase 1 clinical trials in healthy Chinese and Japanese subjects.British journal of clinical pharmacology · 2021Trial
- Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker variables in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study.Annals of the rheumatic diseases · 2019Trial
- Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Rising Doses of BI 655064, an Antagonistic Anti-CD40 Antibody, in Healthy Subjects: A Potential Novel Treatment for Autoimmune Diseases.Journal of clinical pharmacology · 2018Trial
- Emerging Therapeutics in Rheumatoid Arthritis.Current rheumatology reports · 2026Review
- Clinical applications and challenges of CD40/CD40L signaling regulation in autoimmune diseases.Frontiers in immunology · 2026Review
- Immune checkpoint imbalance in ANCA-associated vasculitis: insights into disease activity and precision immunotherapy.Frontiers in medicine · 2026Review
- Importance of B cells (Review).International journal of molecular medicine · 2026Review
- Use of Bayesian techniques in clinical trials for rheumatoid arthritis and systemic sclerosis: a scoping review.BMC rheumatology · 2025Article
- Investigation of Novel Therapeutic Targets for Rheumatoid Arthritis Through Human Plasma Proteome.Biomedicines · 2025Article
- Molecule Formats of B-Cell Targeting Biologics: Applications in Autoimmune Disease Treatment and Impacts on Manufacturability.Pharmaceutics · 2025Review
- Targeting the TNF and TNFR superfamilies in autoimmune disease and cancer.Nature reviews. Drug discovery · 2024Review
- Implications of CD154 and Its Receptors in the Pathogenesis and Treatment of Systemic Lupus Erythematosus.Cells · 2024Review
- Costimulatory and Coinhibitory Immune Checkpoints in Atherosclerosis: Therapeutic Targets in Atherosclerosis?JACC. Basic to translational science · 2024Review
- New molecular targets in the treatment of rheumatoid arthritis.Current opinion in rheumatology · 2024Review
- Machine learning and molecular subtype analyses provide insights into PANoptosis-associated genes in rheumatoid arthritis.Arthritis research & therapy · 2023Article
- The bidirectional immune crosstalk in metabolic dysfunction-associated steatotic liver disease.Cell metabolism · 2023Review
- Targeting immune checkpoints in anti-neutrophil cytoplasmic antibodies associated vasculitis: the potential therapeutic targets in the future.Frontiers in immunology · 2023Review
- Targeting B cells and plasma cells in autoimmune diseases: From established treatments to novel therapeutic approaches.European journal of immunology · 2023Review
- Activation Markers on B and T Cells and Immune Checkpoints in Autoimmune Rheumatic Diseases.International journal of molecular sciences · 2022Review
- Targeting TNature immunology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 8 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo evaluate the safety, efficacy and therapeutic mechanism of BI 655064, an antagonistic anti-CD40 monoclonal antibody, in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR).
methodsIn total, 67 patients were randomised to receive weekly subcutaneous doses of 120 mg BI 655064 (n=44) or placebo (n=23) for 12 weeks. The primary endpoint was the proportion of patients who achieved 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Safety was assessed in patients who received at least one dose of study drug.
resultsAt week 12, the primary endpoint was not met, with 68.2% of patients treated with BI 655064 achieving an ACR20 vs 45.5% with placebo (p=0.064); using Bayesian analysis, the posterior probability of seeing a difference greater than 35% was 42.9%. BI 655064 was associated with greater changes in CD40-CD40L pathway-related markers, including reductions in inflammatory and bone resorption markers (interleukin-6, matrix metalloproteinase-3, receptor activator of nuclear factor-κB ligand), concentration of autoantibodies (immunoglobulin [Ig]G rheumatoid factor [RF], IgM RF, IgA RF) and CD95+ activated B-cell subsets. No serious adverse events (AEs) related to BI 655064 treatment or thromboembolic events occurred; reported AEs were mainly of mild intensity.
conclusionAlthough blockade of the CD40-CD40L pathway with BI 655064 in MTX-IR patients with RA resulted in marked changes in clinical and biological parameters, including reductions in activated B-cells, autoantibody production and inflammatory and bone resorption markers, with a favourable safety profile, clinical efficacy was not demonstrated in this small phase IIa study. TRIAL REGISTRATION NUMBER: NCT01751776.
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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.