Trial reportJCI insight2019
Immunomodulatory activity of humanized anti-IL-7R monoclonal antibody RN168 in subjects with type 1 diabetes.
Trial report in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02038764 (A Phase 1 Study To Evaluate The Safety, Tolerability, Immunogenicity, Pharmacokinetics And Pharmacodynamics Of Multiple Ascending Doses Of Pf-06342674), which is not on this 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.
A Phase 1 Study To Evaluate The Safety, Tolerability, Immunogenicity, Pharmacokinetics And Pharmacodynamics Of Multiple Ascending Doses Of Pf-06342674 (rn168) In Adults With Type 1 Diabetes
Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals.Science translational medicine · 2021Trial
- Model-Based Characterization of the Pharmacokinetics, Target Engagement Biomarkers, and Immunomodulatory Activity of PF-06342674, a Humanized mAb Against IL-7 Receptor-α, in Adults with Type 1 Diabetes.The AAPS journal · 2020Trial
- Cell-intrinsic IL-7Rα deficiency in Foxp3+ Tregs increases type 1 diabetes incidence in NOD mice.ImmunoHorizons · 2026Article
- The Interleukin-7 Receptor Signaling Pathway and Its Perturbation in Immunodeficiency, Autoimmune Disease and Lymphoid Malignancy.Biomolecules · 2026Review
- Memory CD4Frontiers in immunology · 2026Review
- CD47 signaling in aging and age-related diseases: mechanisms, challenges, and therapeutic opportunities.Biogerontology · 2025Review
- Optimizing antibody stability and efficacy in CD47- SIRPα inhibition via computational approaches.Molecular diversity · 2025Article
- Comparative Efficacy of Interleukin-7 and -15 Blockade in Alleviating Experimental Chronic Uveitis and Suppressing Pathogenic Memory CD4+ T Cells.Investigative ophthalmology & visual science · 2025Article
- Molecular roles in membrane receptor signaling pathways and cascade reactions in chondrocytes: a review.Journal of molecular histology · 2025Review
- CONSORT-DEFINE explanation and elaboration: recommendations for enhancing reporting quality and impact of early phase dose-finding clinical trials.EClinicalMedicine · 2025Article
- IL-7 in autoimmune diseases: mechanisms and therapeutic potential.Frontiers in immunology · 2025Review
- LRH-1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype.Clinical and translational medicine · 2024Article
- Sequential immunotherapy: towards cures for autoimmunity.Nature reviews. Drug discovery · 2024Review
- Article
- Identification of key genes and immune infiltration of diabetic peripheral neuropathy in mice and humans based on bioinformatics analysis.Frontiers in endocrinology · 2024Article
- Baseline gene signatures of reactogenicity to Ebola vaccination: a machine learning approach across multiple cohorts.Frontiers in immunology · 2023Article
- Neural Stem Cells Secretome Increased Neurogenesis and Behavioral Performance and the Activation of Wnt/β-Catenin Signaling Pathway in Mouse Model of Alzheimer's Disease.Neuromolecular medicine · 2022Article
- The Role of Interleukins in the Pathogenesis of Dermatological Immune-Mediated Diseases.Advances in therapy · 2022Review
- Tolerogenic nanoparticles mitigate the formation of anti-drug antibodies against pegylated uricase in patients with hyperuricemia.Nature communications · 2022Article
- Targeting T Follicular Helper Cells to Control Humoral Allogeneic Immunity.Transplantation · 2021Review
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 5 institutions in 1 country.
Funding
Abstract
backgroundThe cytokine IL-7 is critical for T cell development and function. We performed a Phase Ib study in patients with type 1 diabetes (T1D) to evaluate how blockade of IL-7 would affect immune cells and relevant clinical responses.
methodsThirty-seven subjects with T1D received s.c. RN168, a monoclonal antibody that blocks the IL -7 receptor α (IL7Rα) in a dose-escalating study.
resultsBetween 90% and 100% IL-7R occupancy and near-complete inhibition of pSTAT5 was observed at doses of RN168 1 mg/kg every other week (Q2wk) and greater. There was a significant decline in CD4+ and CD8+ effector and central memory T cells and CD4+ naive cells, but there were fewer effects on CD8+ naive T cells. The ratios of Tregs to CD4+ or CD8+ effector and central memory T cells versus baseline were increased. RNA sequencing analysis showed downmodulation of genes associated with activation, survival, and differentiation of T cells. Expression of the antiapoptotic protein Bcl-2 was reduced. The majority of treatment-emergent adverse events (TEAEs) were mild and not treatment related. Four subjects became anti-EBV IgG+ after RN168, and 2 had symptoms of active infection. The immunologic response to tetanus toxoid was preserved at doses of 1 and 3 mg/kg Q2wk but reduced at higher doses.
conclusionsThis trial shows that, at dosages of 1-3 mg/kg, RN168 selectively inhibits the survival and activity of memory T cells while preserving naive T cells and Tregs. These immunologic effects may serve to eliminate pathologic T cells in autoimmune diseases.
trial registrationNCT02038764.
fundingPfizer Inc.
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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.