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. 2020 Jun 16;12(1):1770018. doi: 10.1080/19420862.2020.1770018

Table 2.

Estimated JNJ-8104, CNTO148 and CNTO 6785 cynomolgus monkey PK/TE model parameters (mean, residual standard error%) and predicted human parameters.

Parameter (unit) JNJ-8104
Human, predicted
(observed human PK)
JNJ-8104
Human, predicted
(allometric scaling)
JNJ-8104
Cyno, estimated
Golimumab
Cyno, estimated
CNTO 6785
Cyno, estimated
CL (L/day/kg) 0.00549 0.0048 * 0.0077 (4%) 0.0131 (10%) 0.0072 (14%)
V1 (L/kg) 0.0464 0.0375 * 0.0375 (5%) 0.0588 (4%) 0.0405 (6%)
V2 (L/kg) 0.0341 0.0217 * 0.0217 (9%) 0.0342 (9%) 0.0302 (5%)
Q (L/day/kg) 0.00598 0.0140 * 0.0224 (11%) 0.0353 (11%) 0.023 (9%)
TNFα          
kdeg (1/day) 271.18 * 271.18 * 596 ● 596 ●  
Baseline (pg/mL) 0.9^^ 0.9^^ 0.612 ^ 0.612 ^  
kel_complex (1/day) 0.12 0.17* 0.365 ● 0.365 ●  
KD (pM) 1610 ʘ 1610 ʘ 1610 (10%) 65.7 (10%)  
IL-17A          
kdeg (1/day) 45.50 * 45.50 * 100 #   100 (31%)
Baseline (pg/mL) 1.365^^^ 1.365^^^ 0.763 (29%)   1.365 ^
kel_complex (1/day) 0.12 0.14 * 0.317 (25%)   0.504 (39%)
KD (pM) 254 ʘ 254 ʘ 254 (21%)   38.9 (41%)

The PK data points under apparent impact of ADA were excluded for estimating human PK parameters based on JNJ-61178104 observed PK in the FIH study.

kel_complex was based on the estimated human PK parameters assuming that kel_complex for both targets was the same as the elimination rate constant of JNJ-8104 (e.g., calculated as CL/V1).

*Scaled from JNJ-8104 cyno parameters using BW-based allometric scaling with fixed exponents.

ʘ fixed at the estimated parameter values based on JNJ-8104 cyno model fitting.

^^ fixed at the reported population median value for TNFα baseline in RA patients.40

^^^ assumed to be the same as cynos and fixed at the observed mean IL-17A baseline in cynos

● fixed based on mathematical derivations using observed data, see section “TMDD model for TNFα” for details.

^ fixed at the observed mean baseline levels for TNFα or IL-17A in cynos

# fixed at the estimated parameter value based on CNTO 6785 cyno model fitting.