Table 1.
Animal Studies: Antitoxin Monotherapy
| Study | Study Design | Antitoxin | Trigger for Treatment | Treatment | Outcome (No. Survived/ No. Treated) | P valuea |
|---|---|---|---|---|---|---|
| Nonhuman Primates: treatment at detection of serum protective antigen (PA) | ||||||
| 32, 33 | Cynomolgus macaques, randomized, placebo-controlled | Anthrasil | Detection of serum PA | IVIG | 1/16 (6%) | – |
| 7.5 U/kg | 4/15 (27%) | 0.1462 | ||||
| 15 U/kg | 7/16 (44%) | 0.0373 | ||||
| 30 U/kg | 10/14 (71%) | 0.0009 | ||||
|
| ||||||
| 30 | Cynomolgus macaques, placebo-controlled | Thravixa | Detection of serum PA (31–49 h postexposure) | Controls | 0/8 (0.0%) | – |
| 1 mg/kg | 6/10 (60.0%) | 0.0385 | ||||
| 5 mg/kg | 6/9 (66.7%) | 0.0385 | ||||
| 10 mg/kg | 4/10 (40.0%) | n.s. | ||||
| 20 mg/kg | 6/10 (60.0%) | 0.0385 | ||||
|
| ||||||
| 26, 29 | Cynomolgus macaques, randomized, blinded, placebo-controlled | Raxibacumab | Detection of serum PA (avg. 39 h postexposure) | Controls | 0/12 (0.0%) | – |
| 20 mg/kg | 7/14 (50.0%) | 0.0064 | ||||
| 40 mg/kg | 9/14 (64.3%) | <0.0007 | ||||
|
| ||||||
| 31 | Cynomolgus macaques, blinded, randomized, placebo-controlled | Anthrivig | Detection of serum PA (avg. 48 h postexposure) | Gamunex | 0/6 (0.0%) | – |
| 7.1 mg/kg | 2/6 (33.3%) | n.s. | ||||
| 14.2 mg/kg | 1/6 (16.7%) | n.s. | ||||
| 21.3 mg/kg | 2/6 (33.3%) | n.s. | ||||
|
| ||||||
| Nonhuman Primates: treatment at preset time points | ||||||
| 34 | Cynomolgus macaques, randomized, placebo- controlled | Anthim | 48 h postexposure | Controls | 1/10 (10.0%) | – |
| 16 mg/kg | 4/14 (28.6%) | – | ||||
|
| ||||||
| Rabbits: treatment at detection of significant increase in body temperature (SIBT) or serum protective antigen (PA) | ||||||
| 30 | New Zealand white rabbits, placebo-controlled | Thravixa | Detection of SIBT or serum PA (geometric mean: 24–48 h postexposure) | Controls | 0/6 (0.0%) | – |
| 1 mg/kg | 3/9 (33.3%) | n.s. | ||||
| 5 mg/kg | 12/13 (92.3%) | <0.05 | ||||
| 10 mg/kg | 10/11 (90.9%) | <0.05 | ||||
| 20 mg/kg | 6/ 9 (66.7%) | <0.05 | ||||
|
| ||||||
| 23 | New Zealand white rabbits, untreated controls | Thravixa | Detection of SIBT (avg. 27 h postexposure) | Controls | 0/9 (0.0%) | – |
| 8 mg/kg | 9/10 (90.0%) | <0.001 | ||||
|
| ||||||
| 23 | New Zealand white rabbits, untreated controls | Thravixa | Detection of SIBT (avg. 27 h postexposure), 6 h or 12 h post-SIBT | Controls | 0/6 (0.0%) | – |
| 10 mg/kg at SIBT | 5/6 (83.3%) | <0.05 | ||||
| 10 mg/kg 6 h post-SIBT | 6/6 (100.0%) | <0.05 | ||||
| 10 mg/kg 12 h post-SIBT | 4/5 (80.0.%) | <0.05 | ||||
|
| ||||||
| 31 | New Zealand white rabbits, open-label, randomized, placebo-controlled | Anthrivig | Detection of SIBT (avg. 28 h postexposure) | Gamunex | 0/8 (0.0%) | – |
| 7.1 mg/kg | 0/8 (0.0%) | – | ||||
| 14.2 mg/kg | 6/8 (75.0%) | <0.05 | ||||
| 21.3 mg/kg | 2/8 (25.0%) | <0.05 | ||||
|
| ||||||
| 26, 29 | New Zealand white rabbits, randomized, open-label, placebo-controlled | Raxibacumab | Detection of SIBT or serum PA (avg. 30 h postexposure) | Controls | 0/17 (0.0%) | – |
| 20 mg/kg | 5/18 (27.8%) | 0.0455 | ||||
| 40 mg/kg | 8/18 (44.4%) | 0.0029 | ||||
|
| ||||||
| 29 | New Zealand white rabbits, randomized, double-blind, placebo-controlled | Raxibacumab | Detection of SIBT or serum PA (avg. 30 h postexposure) | Controls | 0/24 (0.0%) | – |
| 40 mg/kg | 11/24 (45.8%) | <0.0001 | ||||
|
| ||||||
| 32, 33 | New Zealand white rabbits, Placebo-controlled | Anthrasil | Detection of serum PA (average 32.4 h postexposure) | IVIG | 1/48 (2%) | – |
| 15 U/kg | 13/50 (26%) | 0.0009 | ||||
|
| ||||||
| Rabbits: treatment at preset time points | ||||||
| 32, 33 | New Zealand white rabbits, placebo-controlled | Anthrasil | 30 h postexposure | IVIG | 0/10 (0%) | – |
| 7.5 U/kg | 4/14 (29%) | 0.0489 | ||||
| 15 U/kg | 6/14 (43%) | 0.0239 | ||||
| 30 U/kg | 5/14 (36%) | 0.0407 | ||||
|
| ||||||
| 35, 36 | New Zealand white rabbits, placebo-controlled | Raxibacumab | 36 h postexposure | Controls | 1/12 (8.3%) | – |
| 40 mg/kg | 5/12 (41.7%) | 0.1550 | ||||
|
| ||||||
| 35, 36 | New Zealand white rabbits, placebo-controlled | Raxibacumab | 36 h postexposure | Controls | 0/12 (0.0%) | – |
| 20 mg/kg | 0/12 (0.0%) | 1.0000 | ||||
|
| ||||||
| 38 | Dutch Belted rabbits, untreated controls | Thravixa | 36 h postexposure | Controls | 0/6 (0.0%) | – |
| 2 mg/kg | 2/6 (33.0%) | n.s. | ||||
|
| ||||||
| 38 | Dutch Belted rabbits, untreated controls | Thravixa | 36 h postexposure | Controls | 0/6 (0.0%) | – |
| 0.5 mg/kg | 0/6 (0.0%) | n.s. | ||||
|
| ||||||
| 37 | New Zealand white rabbits, randomized, placebo-controlled | Anthim | 36 h or 48 h postexposure | Controls | 0/10 (0.0%) | – |
| 10 mg at 36 h | 5/10 (50.0%) | 0.041 | ||||
| 10 mg at 48 h | 3/7 (42.9%) | 0.424 | ||||
|
| ||||||
| 39 | Dutch Belted rabbits, placebo-controlled | Thravixa | 48 h postexposure | Controls | 0/5 (0.0%) | – |
| 10 mg/kg | 3/5 (60.0%) | n.s. | ||||
|
| ||||||
| 40 | New Zealand white rabbits, placebo-controlled | Valortim | 48 h postexposure | Controls | 0/10 (0.0%) | – |
| 10 mg/kg | 3/7 (42.9%) | – | ||||
a
p-value Fisher’s Exact Test: compared the treatment group with the control group; n.s. = not significant.