Phase 1b Study of the Safety, Pharmacokinetics, and Disease-related Outcomes of the Matrix Metalloproteinase-9 Inhibitor Andecaliximab in Patients With Rheumatoid Arthritis
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu klinické zkoušky, fáze I, časopisecké články, multicentrická studie, randomizované kontrolované studie, práce podpořená grantem
PubMed
29287749
DOI
10.1016/j.clinthera.2017.11.011
PII: S0149-2918(17)31102-5
Knihovny.cz E-zdroje
- Klíčová slova
- autoimmune diseases, cartilage matrix, matrix metalloproteinase-9, pharmacokinetics, rheumatoid arthritis, therapeutic antibody,
- MeSH
- antirevmatika * škodlivé účinky farmakokinetika terapeutické užití MeSH
- dvojitá slepá metoda MeSH
- humanizované monoklonální protilátky MeSH
- inhibitory matrixových metaloproteinas * škodlivé účinky farmakokinetika terapeutické užití MeSH
- intravenózní infuze MeSH
- lidé středního věku MeSH
- lidé MeSH
- matrixová metaloproteinasa 9 metabolismus MeSH
- monoklonální protilátky * škodlivé účinky farmakokinetika terapeutické užití MeSH
- revmatoidní artritida farmakoterapie metabolismus MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze I MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- andecaliximab MeSH Prohlížeč
- antirevmatika * MeSH
- humanizované monoklonální protilátky MeSH
- inhibitory matrixových metaloproteinas * MeSH
- matrixová metaloproteinasa 9 MeSH
- monoklonální protilátky * MeSH
PURPOSE: Andecaliximab (GS-5745) is a highly selective monoclonal antibody against matrix metalloproteinase-9 (MMP9), a proteolytic enzyme implicated in the pathogenesis of rheumatoid arthritis (RA). This study assessed the safety and pharmacokinetic (PK) parameters of andecaliximab in patients with RA and evaluated the effects of andecaliximab treatment on exploratory disease biomarkers. METHODS: In this double-blind, Phase 1b trial, patients with active RA were randomized (4:1) to receive 400-mg andecaliximab or placebo every 2 weeks for a total of 3 intravenous infusions. The primary and secondary end points were safety and the PK parameters of andecaliximab, respectively. Data were summarized by using descriptive statistics. FINDINGS: A total of 18 patients were randomized; 15 received andecaliximab (participants with confirmed RA diagnosis without current administration of a biologic DMARD a biologic DMARD (disease-modifying antirheumatic drug), aged 18 to 70 years old, weighing >45 to <120 kg). No deaths, serious adverse events, or study discontinuations occurred. All reported adverse events were grade 1 or grade 2 in severity. Mean plasma andecaliximab exposure was 587 d · µg/mL and 878 d · µg/mL at days 1 and 29, respectively, suggesting moderate accumulation. The median terminal t1/2 was 5.65 days; mean volume of distribution at steady state was 4560 mL. Mean MMP9 coverage (the percentage of total plasma MMP9 bound by therapeutic antibody) was maintained at ~80% after the first administration of andecaliximab. IMPLICATIONS: Andecaliximab administered as 3 infusions over 29 days was generally safe and well tolerated in patients with RA. The majority of total plasma MMP9 was bound by andecaliximab after the first administration. Clinical studies of increased treatment duration in larger patient cohorts are warranted. ClinicalTrials.gov identifier: NCT02176876. Registered on 25 June 2014.
Gilead Sciences Inc Foster City California USA
Pharmaceutical Research Associates CZ s r o Prague Czech Republic
Citace poskytuje Crossref.org
ClinicalTrials.gov
NCT02176876
