TABLE 1.
PK parameters of the final popPK model developed using data from patients with primary HLH participating in the NI‐0501‐04/‐05 studies a
| Parameter | Description | Estimate (95% CI) | RSE, % |
|---|---|---|---|
| CLL, L/h/70 kg | Linear clearance | 0.0116 (0.00486‐0.0183) | 29.7 |
| CLNL, L/h/70 kg | Nonlinear clearance (IFNγ‐dependent) | 0.133 (0.0456‐0.220) | 33.5 |
| V1, L/70 kg | Central volume of distribution | 4.16 (3.80‐4.52) | 4.4 |
| Q, L/h/70 kg | Intercompartmental clearance | 0.102 (0.0495‐0.155) | 26.3 |
| V2, L/70 kg | Peripheral volume of distribution | 5.55 (3.30‐7.80) | 20.7 |
| CLNL_IFNγ | Influence of IFNγ on CLNL (power function) | +0.746 (0.567‐0.925) | 12.3 |
| CL_BWV_BW | Allometric exponent of body weight on CLs | +0.886 (0.680‐1.09) | 11.9 |
| Allometric exponent of body weight on vs | 1 fixed | … | |
| IIV | Estimate (IIV %) | Shrinkage, % | |
| OMEGA2_CLI | Variance of CL | 0.240 (49.0) | 4.1 |
| OMEGA2_V1 | Variance of V1 | 0.0721 (26.9) | 7.1 |
| OMEGA2_V2 | Variance of V2 | 0.766 (87.5) | 5.4 |
| OMEGA2_V1_V2 | Correlation (V1/V2) | +0.728 (−) | … |
| RSV | Estimate (RSV %) | Shrinkage, % | |
| SIGMA | SD of residual (additive in log domain) | 0.306 (30.6) | 2.4 |
Note: CL = (CLL + CLNL × (total IFNγ/1,000,000)^CLNL_IFNγ) × (BW/70)^CL_BW with total IFNγ in pg/mL and BW in kg.
Abbreviations: BW, body weight; CI, confidence interval; CL, clearance; CLL, linear clearance; CLNL, nonlinear clearance; HLH, hemophagocytic lymphohistiocytosis; IFNγ, interferon‐γ; IIV, interindividual variability; RSE, relative standard error; RSV, residual variability; SD, standard deviation; V, volume of distribution.
Model developed using 2414 measurements of emapalumab concentrations from the 33 patients with primary HLH treated in the NI‐0501‐04 study and 16 HLH patients who received emapalumab in compassionate use. Objective function value = −2851.507.