Abstract
Objective To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABT-981, a human dual variable domain immunoglobulin simultaneously targeting interleukin (IL)-1α and IL-1β, in patients with knee osteoarthritis (OA). Method This was a randomized, double-blind, placebo-controlled, single-center study of multiple subcutaneous (SC) injections of ABT-981 in patients with mild-to-moderate OA of the knee (NCT01668511). Three cohorts received ABT-981 (0.3, 1, or 3 mg/kg) or placebo every other week for a total of four SC injections, and one cohort received ABT-981 (3 mg/kg) or placebo every 4 weeks for a total of three SC injections. Assessment of safety and tolerability were the primary objectives. A panel of serum and urine biomarkers of inflammation and joint degradation were evaluated. Results A total of 36 patients were randomized (ABT-981, n = 28; placebo, n = 8); 31 (86%) completed the study. Adverse event (AE) rates were comparable between ABT-981 and placebo (54% vs 63%). The most common AE reported with ABT-981 vs placebo was injection site erythema (14% vs 0%). ABT-981 significantly reduced absolute neutrophil count and serum concentrations of IL-1α/IL-1β, high-sensitivity C-reactive protein, and matrix metalloproteinase (MMP)-derived type 1 collagen. Serum concentrations of MMP-derived type 3 collagen and MMP-degraded C-reactive protein demonstrated decreasing trends with ABT-981. Antidrug antibodies were found in 37% of patients but were not associated with the incidence or severity of AEs. Conclusion ABT-981 was generally well tolerated in patients with knee OA and engaged relevant tissue targets, eliciting an anti-inflammatory response. Consequently, ABT-981 may provide clinical benefit to patients with inflammation-driven OA.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1952-1961 |
| Number of pages | 10 |
| Journal | Osteoarthritis and Cartilage |
| Volume | 25 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 1 2017 |
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Keywords
- ABT-981
- Clinical study
- Interleukin-1
- Osteoarthritis
- Pharmacokinetic
- Safety
ASJC Scopus subject areas
- Rheumatology
- Biomedical Engineering
- Orthopedics and Sports Medicine
Cite this
Safety, tolerability, and pharmacodynamics of an anti-interleukin-1α/β dual variable domain immunoglobulin in patients with osteoarthritis of the knee : a randomized phase 1 study. / Wang, S. X.; Abramson, S. B.; Attur, M.; Karsdal, M. A.; Preston, Richard A; Lozada, Carlos; Kosloski, M. P.; Hong, F.; Jiang, P.; Saltarelli, M. J.; Hendrickson, B. A.; Medema, J. K.
In: Osteoarthritis and Cartilage, Vol. 25, No. 12, 01.12.2017, p. 1952-1961.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Safety, tolerability, and pharmacodynamics of an anti-interleukin-1α/β dual variable domain immunoglobulin in patients with osteoarthritis of the knee
T2 - a randomized phase 1 study
AU - Wang, S. X.
AU - Abramson, S. B.
AU - Attur, M.
AU - Karsdal, M. A.
AU - Preston, Richard A
AU - Lozada, Carlos
AU - Kosloski, M. P.
AU - Hong, F.
AU - Jiang, P.
AU - Saltarelli, M. J.
AU - Hendrickson, B. A.
AU - Medema, J. K.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Objective To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABT-981, a human dual variable domain immunoglobulin simultaneously targeting interleukin (IL)-1α and IL-1β, in patients with knee osteoarthritis (OA). Method This was a randomized, double-blind, placebo-controlled, single-center study of multiple subcutaneous (SC) injections of ABT-981 in patients with mild-to-moderate OA of the knee (NCT01668511). Three cohorts received ABT-981 (0.3, 1, or 3 mg/kg) or placebo every other week for a total of four SC injections, and one cohort received ABT-981 (3 mg/kg) or placebo every 4 weeks for a total of three SC injections. Assessment of safety and tolerability were the primary objectives. A panel of serum and urine biomarkers of inflammation and joint degradation were evaluated. Results A total of 36 patients were randomized (ABT-981, n = 28; placebo, n = 8); 31 (86%) completed the study. Adverse event (AE) rates were comparable between ABT-981 and placebo (54% vs 63%). The most common AE reported with ABT-981 vs placebo was injection site erythema (14% vs 0%). ABT-981 significantly reduced absolute neutrophil count and serum concentrations of IL-1α/IL-1β, high-sensitivity C-reactive protein, and matrix metalloproteinase (MMP)-derived type 1 collagen. Serum concentrations of MMP-derived type 3 collagen and MMP-degraded C-reactive protein demonstrated decreasing trends with ABT-981. Antidrug antibodies were found in 37% of patients but were not associated with the incidence or severity of AEs. Conclusion ABT-981 was generally well tolerated in patients with knee OA and engaged relevant tissue targets, eliciting an anti-inflammatory response. Consequently, ABT-981 may provide clinical benefit to patients with inflammation-driven OA.
AB - Objective To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABT-981, a human dual variable domain immunoglobulin simultaneously targeting interleukin (IL)-1α and IL-1β, in patients with knee osteoarthritis (OA). Method This was a randomized, double-blind, placebo-controlled, single-center study of multiple subcutaneous (SC) injections of ABT-981 in patients with mild-to-moderate OA of the knee (NCT01668511). Three cohorts received ABT-981 (0.3, 1, or 3 mg/kg) or placebo every other week for a total of four SC injections, and one cohort received ABT-981 (3 mg/kg) or placebo every 4 weeks for a total of three SC injections. Assessment of safety and tolerability were the primary objectives. A panel of serum and urine biomarkers of inflammation and joint degradation were evaluated. Results A total of 36 patients were randomized (ABT-981, n = 28; placebo, n = 8); 31 (86%) completed the study. Adverse event (AE) rates were comparable between ABT-981 and placebo (54% vs 63%). The most common AE reported with ABT-981 vs placebo was injection site erythema (14% vs 0%). ABT-981 significantly reduced absolute neutrophil count and serum concentrations of IL-1α/IL-1β, high-sensitivity C-reactive protein, and matrix metalloproteinase (MMP)-derived type 1 collagen. Serum concentrations of MMP-derived type 3 collagen and MMP-degraded C-reactive protein demonstrated decreasing trends with ABT-981. Antidrug antibodies were found in 37% of patients but were not associated with the incidence or severity of AEs. Conclusion ABT-981 was generally well tolerated in patients with knee OA and engaged relevant tissue targets, eliciting an anti-inflammatory response. Consequently, ABT-981 may provide clinical benefit to patients with inflammation-driven OA.
KW - ABT-981
KW - Clinical study
KW - Interleukin-1
KW - Osteoarthritis
KW - Pharmacokinetic
KW - Safety
UR - http://www.scopus.com/inward/record.url?scp=85031745402&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85031745402&partnerID=8YFLogxK
U2 - 10.1016/j.joca.2017.09.007
DO - 10.1016/j.joca.2017.09.007
M3 - Article
C2 - 28964890
AN - SCOPUS:85031745402
VL - 25
SP - 1952
EP - 1961
JO - Osteoarthritis and Cartilage
JF - Osteoarthritis and Cartilage
SN - 1063-4584
IS - 12
ER -