Table 2.
Primary efficacy analysesa.
| Efficacy outcome | LLDT-8 (1 mg) | LLDT-8 (0.5 mg) | Placebo |
|---|---|---|---|
| Primary endpoints | |||
| Change in the CD4 counts at Wk 48, cells/mm3 | |||
| Mean | 62 (40, 84) | 50 (29, 70) | 29 (13, 45) |
| LSMEAN | 63 (41, 84) | 49 (29, 68) | 32 (13, 51) |
| LSMEAN Difference | 14 (−14, 43)b; 30 (2, 59)c | 16 (−10, 43)c | – |
| P-value | 0.338b; 0.036b | 0.224c | – |
| Proportion of patients with the CD4 count increased by ≥ 50 cells/mm3 at Wk 48 | |||
| No. (%) | 23 (50.0) | 23 (45.1) | 18 (34.6) |
| P-value | 0.584b; 0.077c | 0.302c | – |
| Change in inflammatory factors (IP-10, hsCRP, IL-6) at Wk 48d | |||
| IP-10, pg/ml | |||
| Mean | −72.1 (−99.9, −44.3) | −42.5 (−64.3, −20.7) | −22.8 (−48.7, 3.1) |
| LSMEAN | −72.1 (−97.7, −46.5) | −42.5 (−66.8, −18.2) | −22.8 (−47.1, 1.5) |
| LSMEAN Difference | −29.6 (−64.9, 5.7)b; −49.3 (−84.6, −14.0)c | −19.7 (−54.0, 14.7)c | – |
| P-value | 0.100b; 0.007c | 0.260c | – |
| hsCRP, mg/L | |||
| Mean | −2.7 (−8.0, 2.5) | −0.5 (−1.0, −0.1) | −0.3 (−1.2, −0.6) |
| LSMEAN | −2.7 (−5.7, 0.2) | −0.5 (−3.3, −2.3) | −0.3 (−3.1, −2.5) |
| LSMEAN Difference | −2.2 (−6.3, 1.8)b; −2.5 (−6.5, 1.6)c | −0.3 (−4.2, 3.7)c | – |
| P-value | 0.288b; 0.234c | 0.895c | – |
| IL-6, pg/ml | |||
| Mean | −2.1 (−7.2, 2.9) | 0.7 (−0.6, 1.9) | 2.6 (−2.4, 7.6) |
| LSMEAN | −2.1 (−6.3, 2.0) | 0.7 (−3.3, 4.6) | 2.6 (−1.3, 6.5) |
| LSMEAN Difference | −2.8 (−8.5, 3.0)b; −4.7 (−10.5, 1.0)c | −1.9 (−7.5, 3.6)c | – |
| P-value | 0.340b; 0.106c | 0.493c | – |
| Secondary endpoints | |||
| Change in the CD4/CD8 ratio at Wk 24 | |||
| Mean | 0.04 (0.01, 0.07) | 0.04 (0, 0.08) | −0.01 (−0.04, 0.01) |
| LSMEAN | 0.04 (0.01, 0.07) | 0.04 (0.01, 0.07) | −0.01 (−0.04, 0.02) |
| LSMEAN Difference | 0 (−0.04, 0.04)b; 0.05 (0.01, 0.10)c | 0.05 (0.01, 0.10)c | – |
| P-value | 0.987b; 0.017c | 0.015 c | – |
| Change in the CD4/CD8 ratio at Wk 48 | |||
| Mean | 0.05 (−0.01, 0.11) | 0.04 (−0.01, 0.09) | 0.04 (0, 0.07) |
| LSMEAN | 0.05 (0, 0.10) | 0.04 (−0.01, 0.09) | 0.04 (−0.01, 0.08) |
| LSMEAN Difference | 1.1 (−0.06, 0.08)b; 2.2 (−0.05, 0.08)c | 0.01 (−0.06, 0.07)c | – |
| P-value | 0.809b; 0.646c | 0.829c | – |
| Proportion of patients with the CD4 count increased by ≥ 20% at Wk 24 | |||
| No. (%) | 21 (45.7) | 26 (51.0) | 10 (19.2) |
| P-value | 0.833b; 0.005c | <0.001c | – |
| Proportion of patients with the CD4 count increased by ≥ 20% at Wk 48 | |||
| No. (%) | 23 (50.0) | 24 (47.1) | 18 (34.6) |
| P-value | 0.874b; 0.240c | 0.423c | – |
| Proportion of patients with the CD4 count <200 cells/mm3 at baseline and increased to ≥ 200 cells/mm3at Wk 24e | |||
| No. (%) | 6 (60.0) | 12 (80.0) | 5 (38.5) |
| P-value | 0.252b; 0.657c | 0.023c | – |
| Proportion of patients with the CD4 count <200 cells/mm3 at baseline and increased to ≥ 200 cells/mm3at Wk 48e | |||
| No. (%) | 9 (90.0) | 11 (73.3) | 9 (69.2) |
| P-value | 0.769b; 0.339c | 0.827c | – |
Abbreviations: LSMEANS: least-squares means; CI: confidence interval; IP-10: Interferon gamma-induced protein 10; hsCRP: high-sensitivity C-reactive protein; IL-6: interleukin 6.
a
The analyses were set for the FAS population. Mean, LSMEAN, and LSMEAN difference were represented as data and 95% CI. LSMEANs Difference and P-values were bversus the LLDT-8 (0.5 mg) group; or cversus the placebo group.
d
LLDT-8 (1 mg) group included 46 patients; LLDT-8 (0·5 mg) group included 51 patients; placebo group included 51 (1 missing baseline data) patients.
e
LLDT-8 (1 mg) group included 10 patients; LLDT-8 (0·5 mg) group included 15 patients; placebo group included 13 patients.