Table 2:
Clinical trials involving therapeutic antibodies/antisera against S. aureus infections*
| Targeta | Name [Company; NCT numberb] |
Study Design | Status (study result) | Interventionc | Ref |
|---|---|---|---|---|---|
| Single component | |||||
| ClfA (adhesin) | Tefibazumab (Aurexis®) [Inhibitex] |
randomized, double-blind, placebo-controlled trial of bacteremia patients receiving standard antibiotic treatment plus Tefibazumab (N = 63) | Phase II (failed) | Huz/mAb (IgG1) | [104] |
| Tefibazumab (Aurexis®) [Inhibitex; NCT00198289] |
dose escalation study of Aurexis® in cystic fibrosis patients chronically colonized with S. aureus in their lung (N = 30) | Phase IIa (failed) | Huz/mAb (IgG1) | i | |
| CP 5 and CP8 (capsular polysaccharides) | AltaStaph™ [Nabi Biopharmaceuticals; NCT00063089] |
randomized, double-blind, placebo-controlled trial involving adult S. aureus bacteremia patients receiving standard treatment plus Altastaph (N = 40) | Phase II (halted) | polyclonal human IgG with high antibody titers against CP5 and CP8, purified from the plasma of healthy donors that have been vaccinated with StaphVAXd | [105] |
| AltaStaph™ [Nabi Biopharmaceuticals; NCT00066989] |
randomized, double-blind, placebo-controlled trial for prevention of nosocomial S. aureus infections in very low birth weight (VLBW) neonates (N = 206) | Phase II (failed) | same as above | [106] | |
| LTA (cell wall component) | Pagibaximab® [Biosynexus; NCT00631800] |
randomized, double-blind, placebo-controlled dose-ranging study on prevention of CoNS and S. aureus sepsis in VLBW neonates (N = 88) | Phase II (finished) | murine/human chimeric mAb | [127] |
| Pagibaximab® [Biosynexus; NCT00646399] |
randomized, double-blind, placebo-controlled study on prevention of staphylococcal sepsis in VLBW neonates (N = 1579) | Phase III (failed) | murine/human chimeric mAb | [108] | |
| WTA (wall teichoic acid) | DSTA4637S [Roche/Genentech; NCT03162250] |
randomized double-blind, placebo-controlled multiple-ascending dose study on safety, tolerability, and pharmacokinetics in S. aureus bacteremia (N = 24) | Phase lb (ongoing) | THIOMAB™ antibody (Hu/mAb; IgG1)-antibiotic conjugate | [114,115] |
| PNAG (cell wall component) | SAR279356 [Sanofi-Aventis; NCT01389700] |
randomized, double-blind, placebo-controlled study to assess a single dose of SAR279356 in ICU patients on mechanical ventilation (N = 7) | Phase IIa (terminated due to difficulty in patient recruitment) | Hu/mAb | ii |
| Hla (toxin) | MEDI4893 (Suvratoxumab) [MedImmune LLC; NCT02296320] |
randomised, double-blind, placebo-controlled, single-dose, dose-ranging study in mechanically ventilated adult subjects (N = 213) | Phase II (ongoing) | Hu/mAb (IgG1) | [111] |
| AR-301 (Salvecin®) [Aridis Pharmaceuticals; NCT01589185] |
randomized, double-blind, placebo-controlled, single dose study of AR-301 as an adjunctive therapy against severe S. aureus-related pneumonia (N = 48) | Phase IIa (successful) | Hu/mAb (IgG1) | iii | |
| GrfA (ABC transporter) | Aurograb® [NeuTec Pharma Ltd./Novartis Pharma AG; NCT00217841] |
randomised, double-blind, placebo-controlled trial of patients with severe, deep-seated staphylococcal infections receiving vancomycin plus Aurograb (N = 180) | Phase II (failed), development stopped | single chain antibody fragment (Fab) | [134,144] |
| Multi-component | |||||
| ClfA (S. aureus), SdrG (S. epidermidis) (adhesins) | INH-A21 (Veronate®) [Inhibitex / Bristol Myers-Squibb; NCT00113191] |
randomized, double-blind, placebo-controlled study of INH-A21 for prevention of staphylococcal late-onset sepsis in VLBW infants (N = 1983) | Phase III (failed) | Pooled human Ig purified from the serum of donors with high titers against ClfA and SdrG | [113] |
| Hla, HlgAB, HlgCB, LukED, LukSF, LukAB (toxins) | ASN100 [Arsanis Biosciences GmbH; NCT02940626] |
randomized, double-blind, single-dose, placebo-controlled study of ASN100 for the prevention of S. aureus pneumonia in heavily-colonized, mechanically ventilated subjects (N = 354) | Phase II (halted) | Hu/mAb combination of ASN-1 (IgG1, crossreactive mAb with affinity for Hla, HlgAB, HlgCB, LukED and LukSF) and ASN-2 (IgG1, mAb against LukAB) | [95,112] |
data based on publications, review of sponsor website information as well as clinical trial data accessible via www.clinicaltrials.gov on 20.08.2018.
Abbreviations: ClfA, clumping factor A; LTA, lipoteichoic acid; PNAG, ß-1,6-poly-N-acetylglucosamine; Hla, α-toxin; SdrG, Serine- aspartate repeat- containing protein G; HlgAB and HlgCB, γ-haemolysin AB and CB; LukED and LukSF, leukotoxin ED and SF; NA, data not available; VLBW, very low birth weight.
ClinicalTrials.gov Identifieriv
Antibodies applied in clinical studies were either murine, chimeric, humanized or human (see Glossary)
StaphVAX® is a bivalent S. aureus vaccine which contains the purified capsular polysaccharides (CPS) types 5 and 8v. Its development was halted by Nabi due to failure in preventing S. aureus infections in kidney disease patients in a confirmatory phase III clinical trialvi.. The company also halted the development of Altastaph™, as it is based on the same capsular polysaccharide technology as StaphVAX®.
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