-
Something wrong with this record ?
Phase 1b Study of the Safety, Pharmacokinetics, and Disease-related Outcomes of the Matrix Metalloproteinase-9 Inhibitor Andecaliximab in Patients With Rheumatoid Arthritis
DL. Gossage, B. Cieslarová, S. Ap, H. Zheng, Y. Xin, P. Lal, G. Chen, V. Smith, JS. Sundy,
Language English Country United States
Document type Clinical Trial, Phase I, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
NLK
ProQuest Central
from 2002-01-01 to 2 months ago
Nursing & Allied Health Database (ProQuest)
from 2002-01-01 to 2 months ago
Health & Medicine (ProQuest)
from 2002-01-01 to 2 months ago
Health Management Database (ProQuest)
from 2002-01-01 to 2 months ago
- MeSH
- Antirheumatic Agents * adverse effects pharmacokinetics therapeutic use MeSH
- Double-Blind Method MeSH
- Matrix Metalloproteinase Inhibitors * adverse effects pharmacokinetics therapeutic use MeSH
- Infusions, Intravenous MeSH
- Middle Aged MeSH
- Humans MeSH
- Matrix Metalloproteinase 9 metabolism MeSH
- Antibodies, Monoclonal * adverse effects pharmacokinetics therapeutic use MeSH
- Arthritis, Rheumatoid drug therapy metabolism MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase I MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial 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
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc18033420
- 003
- CZ-PrNML
- 005
- 20181023111034.0
- 007
- ta
- 008
- 181008s2018 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.clinthera.2017.11.011 $2 doi
- 035 __
- $a (PubMed)29287749
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Gossage, David L $u Gilead Sciences, Inc, Foster City, California, USA. Electronic address: david.gossage@gilead.com.
- 245 10
- $a Phase 1b Study of the Safety, Pharmacokinetics, and Disease-related Outcomes of the Matrix Metalloproteinase-9 Inhibitor Andecaliximab in Patients With Rheumatoid Arthritis / $c DL. Gossage, B. Cieslarová, S. Ap, H. Zheng, Y. Xin, P. Lal, G. Chen, V. Smith, JS. Sundy,
- 520 9_
- $a 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.
- 650 _2
- $a senioři $7 D000368
- 650 12
- $a monoklonální protilátky $x škodlivé účinky $x farmakokinetika $x terapeutické užití $7 D000911
- 650 12
- $a antirevmatika $x škodlivé účinky $x farmakokinetika $x terapeutické užití $7 D018501
- 650 _2
- $a revmatoidní artritida $x farmakoterapie $x metabolismus $7 D001172
- 650 _2
- $a dvojitá slepá metoda $7 D004311
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a intravenózní infuze $7 D007262
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a matrixová metaloproteinasa 9 $x metabolismus $7 D020780
- 650 12
- $a inhibitory matrixových metaloproteinas $x škodlivé účinky $x farmakokinetika $x terapeutické užití $7 D061965
- 650 _2
- $a lidé středního věku $7 D008875
- 655 _2
- $a klinické zkoušky, fáze I $7 D017426
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a multicentrická studie $7 D016448
- 655 _2
- $a randomizované kontrolované studie $7 D016449
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Cieslarová, Blanka $u Pharmaceutical Research Associates, CZ, s.r.o., Prague, Czech Republic.
- 700 1_
- $a Ap, Sophe $u Gilead Sciences, Inc, Foster City, California, USA.
- 700 1_
- $a Zheng, Hao $u Gilead Sciences, Inc, Foster City, California, USA.
- 700 1_
- $a Xin, Yan $u Gilead Sciences, Inc, Foster City, California, USA.
- 700 1_
- $a Lal, Preeti $u Gilead Sciences, Inc, Foster City, California, USA.
- 700 1_
- $a Chen, Guang $u Gilead Sciences, Inc, Foster City, California, USA.
- 700 1_
- $a Smith, Victoria $u Gilead Sciences, Inc, Foster City, California, USA.
- 700 1_
- $a Sundy, John S $u Gilead Sciences, Inc, Foster City, California, USA.
- 773 0_
- $w MED00001165 $t Clinical therapeutics $x 1879-114X $g Roč. 40, č. 1 (2018), s. 156-165.e5
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/29287749 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20181008 $b ABA008
- 991 __
- $a 20181023111541 $b ABA008
- 999 __
- $a ok $b bmc $g 1339455 $s 1030414
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2018 $b 40 $c 1 $d 156-165.e5 $e 20171226 $i 1879-114X $m Clinical therapeutics $n Clin Ther $x MED00001165
- LZP __
- $a Pubmed-20181008
