Trial reportClinical and translational science2022
Determination of a clinically effective evobrutinib dose: Exposure-response analyses of a phase II relapsing multiple sclerosis study.
Trial report in Clinical and translational science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02975349 (A Randomized, Double-Blind, Placebo-Controlled Phase II Study of M2951 With a Parallel, Open-Label, Active Control Group), which is not on this map. Cited by 10 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 Randomized, Double-Blind, Placebo-Controlled Phase II Study of M2951 With a Parallel, Open-Label, Active Control Group (Tecfidera), in Patients With Relapsing Multiple Sclerosis to Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics, and Biological Activity.
Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Efficacy and safety results after >3.5 years of treatment with the Bruton's tyrosine kinase inhibitor evobrutinib in relapsing multiple sclerosis: Long-term follow-up of a Phase II randomised clinical trial with a cerebrospinal fluid sub-study.Multiple sclerosis (Houndmills, Basingstoke, England) · 2024Trial
- Effect of Evobrutinib on Slowly Expanding Lesion Volume in Relapsing Multiple Sclerosis: A Post Hoc Analysis of a Phase 2 Trial.Neurology · 2024Trial
- Determination of a clinically effective evobrutinib dose: Exposure-response analyses of a phase II relapsing multiple sclerosis study.Clinical and translational science · 2022Trial
- Review
- The Role of Pharmacometrics in Advancing the Therapies for Autoimmune Diseases.Pharmaceutics · 2024Review
- BTK inhibition limits microglia-perpetuated CNS inflammation and promotes myelin repair.Acta neuropathologica · 2024Article
- Update and Application of a Deep Learning Model for the Prediction of Interactions between Drugs Used by Patients with Multiple Sclerosis.Pharmaceutics · 2023Article
- Antibody response to SARS-CoV-2 vaccines in patients with relapsing multiple sclerosis treated with evobrutinib: A Bruton's tyrosine kinase inhibitor.Multiple sclerosis (Houndmills, Basingstoke, England) · 2023Article
- Bruton's Tyrosine Kinase Inhibitors (BTKIs): Review of Preclinical Studies and Evaluation of Clinical Trials.Molecules (Basel, Switzerland) · 2023Review
- Navigating a transforming landscape: the evolving role of pharmacovigilance physicians in drug development and implications for future challenges and training requirements.Frontiers in drug safety and regulation · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pharmacometric analysis of the double-blind, randomized, phase II study (NCT02975349) investigating the safety and efficacy of evobrutinib, explored exposure-response relationships and suitable dosing regimens of evobrutinib for relapsing multiple sclerosis. Population pharmacokinetic (PK)/pharmacodynamic modeling was applied to data collected in fasted patients treated with placebo or evobrutinib (25 mg once-daily [q.d.], 75 mg q.d., or 75 mg twice-daily [b.i.d.]) for 24 weeks, followed by a 24-week blinded extension (placebo patients switched to 25 mg q.d.). Model-based exposures for PK and Bruton's tyrosine kinase occupancy (BTKO) were used for exposure-response analyses (maximum 207 patients). PK, BTKO profiles, and annualized relapse rate (ARR) after 48 weeks of treatment under alternative dosing regimens were simulated. Exposure-response modeling identified a relationship between evobrutinib exposure and clinical response for total number of T1 Gd+ and new/enlarging T2 lesions at weeks 12-24, and ARR at week 48. Area under the concentration-time curve over 24 h at steady-state (AUC
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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.