Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
SYN-004 · 2 trials · 4 indications
Percentage of subjects with CDI, based on the protocol definition of CDI (defined as 3 or more unformed stools per 24 hour period and a stool sample being positive for C. difficile toxin A and/or B \[or their respective genes, tcdA and/or tcdB\], based on the clinical site local laboratory results) from Day 1 to the 4-week Follow-up Visit in the SYN-004 treatment group compared to the placebo group, imputing early termination without CDI as not being treatment failures.
Assess potential SYN-004 systemic absorption (if any) by measuring SYN-004 plasma concentrations
Assess potential effects of SYN-004 on systemic antibiotic concentrations by measuring MER, PIP and FEP plasma levels and determining the area under the curve for antibiotic concentrations and time (T) of antibiotic concentration above the minimum inhibitory concentration (MIC) (T\>MIC) using the Clinical and Laboratory Standards Institute (CLSI) MIC susceptibility breakpoint for Enterobacteriaceae and Pseudomonas aeruginosa for each individual participant
Assess the incidence of blood stream infections (bacteremia) with an organism susceptible to MER, PIP/TAZO or FEP while receiving SYN-004 concurrent with the antibiotic the organism is susceptible to, wherein the bacteremia is attributable to a clinical infection with adequate source control (if applicable) and unrelated to a device
Assess the incidence and severity of bacterial intestinal infections other than CDI (such as typhlitis, neutropenic enterocolitis or diverticulitis) while on study drug and study assigned antibiotic
Assess tolerability of SYN-004 and grade 3 or 4 adverse events up to 30 days after the last dose of SYN-004
Overall survival at 30 days after last dose of SYN-004
| Arm | Type | Description |
|---|---|---|
| SYN-004 | EXPERIMENTAL | SYN-004 150 mg |
| Placebo | PLACEBO_COMPARATOR | Matching placebo |
| Placebo + IV Meropenem | PLACEBO_COMPARATOR | Placebo, oral administration, 4 times per day (q6h), beginning on day +1 after HCT until 72-hours after completion of IV Meropenem (MER) |
| SYN-004 + IV Meropenem | ACTIVE_COMPARATOR | SYN-004, oral administration, 150mg, 4 times per day (q6h), beginning on day +1 after HCT until 72-hours after completion of IV Meropenem (MER) |
| Placebo + IV Piperacillin/Tazobactam | PLACEBO_COMPARATOR | Placebo, oral administration, 4 times per day (q6h), beginning on day +1 after HCT until 72-hours after completion of IV Piperacillin/Tazobactam (PIP/TAZO) |
| SYN-004 + IV Piperacillin/Tazobactam | ACTIVE_COMPARATOR | SYN-004, oral administration, 150mg, 4 times per day (q6h), beginning on day +1 after HCT until 72-hours after completion of IV Piperacillin/Tazobactam (PIP/TAZO) |
| Placebo + IV Cefepime | PLACEBO_COMPARATOR | Placebo, oral administration, 4 times per day (q6h), beginning on day +1 after HCT until 72-hours after completion of IV Cefepime (FEP) |
| SYN-004 + Cefepime | ACTIVE_COMPARATOR | SYN-004, oral administration, 150mg, 4 times per day (q6h), beginning on day +1 after HCT until 72-hours after completion of IV Cefepime (FEP) |
| Name | Type | Description |
|---|---|---|
| SYN-004 | DRUG | - |
| Placebo | DRUG | - |
| SYN-004, Ribaxamase or Placebo | BIOLOGICAL | SYN-004 is an oral formulation of a recombinant class-A beta-lactamase that hydrolyzes the beta-lactam ring of susceptible antibiotics that are excreted into the intestines |
Inclusion Criteria: * Expected minimum hospital stay of 5 days * Expected ≥5 day course of intravenous (IV) ceftriaxone alone or in combination with a macrolide * Clinical diagnosis of moderate to severe lower respiratory tract infection consisting of signs and symptoms of a lower respiratory tract...
SYN-004 is an investigational monoclonal antibody developed by Theriva Biologics, Inc. (ticker TOVX). It is being studied for the prevention of acute graft-versus-host reaction following bone marrow transplant and for Clostridium difficile infection, including prevention of CDI in adult patients treated with intravenous beta-lactam antibiotics.
SYN-004 is being studied to prevent Clostridium difficile infection, including in adult patients receiving intravenous beta-lactam antibiotics. A completed Phase 2 trial, NCT02563106, evaluated SYN-004 for the prevention of C. diff in patients with a lower respiratory tract infection across the United States, Bulgaria, Canada, Hungary, Poland, Romania and Serbia.
SYN-004 is developed by Theriva Biologics, Inc., which trades under the ticker TOVX. The company is the sponsor of the clinical program studying the monoclonal antibody in acute graft-versus-host reaction following bone marrow transplant and in Clostridium difficile infection.
SYN-004 is in Phase 1 development. A Phase 1 trial, NCT04692181, is active but not recruiting and is evaluating safety and tolerability in allo-HCT subjects. A separate Phase 2 trial of SYN-004, NCT02563106, has been completed. SYN-004 is investigational and has not been approved by the FDA.
SYN-004 has been studied in two registered trials. NCT04692181 is a Phase 1 safety and tolerability study in allo-HCT subjects that is active but not recruiting, with 36 participants in the United States. NCT02563106 is a completed Phase 2 study for the prevention of C. diff in patients with a lower respiratory tract infection, enrolling 413 participants.
SYN-004 is a monoclonal antibody. It is being developed for prevention of acute graft-versus-host reaction following bone marrow transplant and for Clostridium difficile infection, including prevention of CDI in adult patients being treated with intravenous beta-lactam antibiotics.