SYN-004 Safety and Tolerability in Allo-HCT Subjects

Condition(s) studied

Investigational drug(s) / intervention(s)

SYN-004, Ribaxamase or Placebo: 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

Study summary

Study Objectives:

1. To evaluate the safety and tolerability of oral SYN-004 in adult allogeneic HCT (allo-HCT) recipients who develop fever after conditioning therapy and are treated with IV β-lactam antibiotics meropenem (MER), piperacillin tazobactam (PIP/TAZO), or cefepime (FEP).
2. To evaluate potential absorption of oral SYN-004 into the systemic circulation of allo-HCT recipients and potential SYN-004-mediated alterations to systemic levels and efficacy of IV MER, PIP/TAZO or FEP.
3. To evaluate potential protective effects of SYN-004 on the intestinal microbiome of allo-HCT recipients treated with IV MER, PIP/TAZO or FEP.
4. To obtain preliminary information on potential therapeutic benefits and patient outcomes of SYN-004 in allo-HCT recipients treated with IV MER, PIP/TAZO or FEP

Eligibility

Primary outcome measure(s)

• SYN-004 systemic absorption — No more than 28 days
  Assess potential SYN-004 systemic absorption (if any) by measuring SYN-004 plasma concentrations
• Systemic antibiotic concentrations — Up to 8 hours after IV administration of antibiotic
  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
• Bacteremia — Daily during treatment, and weekly until 30 days after discontinuation of SYN-004 or Placebo
  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
• Bacterial intestinal infections — Daily during treatment, and weekly until 30 days after discontinuation of SYN-004 or Placebo
  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
• Grade 3 or 4 adverse events — Up to 30 days after the last dose of SYN-004 or Placebo
  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 — Up to 30 days after the last dose of SYN-004 or Placebo
  Overall survival at 30 days after last dose of SYN-004

Trial sites (1)