Theriva Announces Positive Outcome Of DSMC Review in Phase 1b/2a Trial of Ribaxamase

Theriva Announces Positive Outcome Of DSMC Review in Phase 1b/2a Trial of Ribaxamase

By, Admin 7 October 2024

Theriva Biologics announces positive outcome of DSMC review in phase 1b/2a trial of ribaxamase in allogeneic HCT recipients

Overview

Theriva Biologics, Inc., a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, announced a positive outcome from the Data and Safety Monitoring Committee (DSMC) review of results from the second Cohort of its phase 1b/2a randomized, double-blinded, placebo-controlled clinical trial of SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant (HCT) recipients for the prevention of acute graft-versus-host-disease (aGVHD).

Detailes on Chohort 2

  • Cohort 2 enrolled 19 patients who received at least 1 dose of study drug (SYN-004 or Placebo randomized 2:1). 
  • Eighteen (18) patients received at least one dose of intravenous (IV) piperacillin/tazobactam and 12 of these patients completed sufficient doses of IV piperacillin/tazobactam to be evaluable towards the study endpoints. 
  • The study is ongoing and remains blinded; however, key findings from blinded data for Cohort 2 are included:
  • Common adverse events
  • Adverse events (AEs) and serious adverse events (SAEs) observed in Cohort 2 were typical of those observed in allo-HCT patients and no AEs or SAEs were determined by the investigators to be related to study drug treatment.
  • A total of 15 SAEs were reported among 10 patients, with the most common SAE being infections and infestations, including sepsis.
  • No patients died within the 30-day follow-up period after the last dose of study drug; 1 patient died 95 days and another 211 days after the last dose of study drug due to cancer relapse and pneumonia respectively (not related to study drug).

Cohort 1 Findings

  • Consistent with the findings from Cohort 1 and previous studies of SYN-004 in healthy volunteers, no patient blood samples were positive for SYN-004 at any timepoint.
  • The pharmacokinetics of piperacillin, which can be metabolized by SYN-004, were as expected for this patient population.

Recommendations for Cohort 3

Based on a review of the safety and pharmacokinetic data, the DSMC has recommended that the study proceed to enroll Cohort 3, in which study drug (SYN-004 or placebo) will be administered in combination with the IV beta-lactam antibiotic cefepime.

Statement from the CEO: Theriva Biologics

  • Steven A. Shallcross, chief executive officer of Theriva Biologics, commented, “These encouraging data support the clinical advancement of SYN-004 and build on the growing data that underscore its therapeutic potential. The first 2 cohorts have shown that active SYN-004 is not found in the blood of allo-HCT patients after repeated oral doses, in part alleviating the concern that SYN-004 might be absorbed in patients with poor intestinal barrier function and potentially interfere with IV antibiotics.
  • We are very grateful for the tremendous support from Dr. Dubberke and his team at Washington University as we pursue additional funding to enable the conduct of the third cohort and continue with the goal of improving standard treatment for these highly susceptible patients by overcoming existing limitations of broad-spectrum IV beta-lactam antibiotics.

Current Trial

  • The ongoing randomized, double-blinded, placebo-controlled phase 1b/2a clinical trial is being conducted at Washington University School of Medicine in St. Louis. 
  • The trial is designed to evaluate the safety, tolerability, and potential absorption of oral SYN-004 (150 mg QID for a maximum of 28 days) into the systemic circulation of allogeneic HCT recipients who receive an IV antibiotic. 
  • To mitigate risk, Cohort 1 of the study administered meropenem as the study-assigned antibiotic. Meropenem is a carbapenem antibiotic that is not metabolized by SYN-004. 
  • Patients in Cohorts 2 were administered piperacillin/tazobactam and Patients in Cohort 3 will be administered cefepime. 
  • Both piperacillin and cefepime can be metabolized by SYN-004. 
  • The trial is also designed to evaluate potential protective effects of SYN-004 on the gut microbiome as well as generate preliminary information on potential therapeutic benefits and patient outcomes of SYN-004 in allogeneic HCT recipients. 
  • The trial is expected to enroll up to 36 participants with three sequential cohorts, each evaluating a different study-assigned IV beta-lactam antibiotic. 
  • Safety and pharmacokinetic data for each Cohort will be reviewed by an independent Data and Safety Monitoring Committee that will make a recommendation on whether to proceed to the next IV antibiotic. 
  • More information on the study is available here (NCT04692181).

The Therapy: SYN-004 (ribaxamase)

  • SYN-004 (ribaxamase) is an oral prophylactic therapy designed to degrade certain IV beta-lactam antibiotics within the GI tract and maintain the natural balance of the gut microbiome for the prevention of Clostridioides difficile infection (CDI), overgrowth of pathogenic organisms, the emergence of antimicrobial resistance (AMR) and acute graft-versus-host-disease (aGVHD) in allogeneic hematopoietic cell transplant (HCT) recipients. 
  • Allogeneic HCT recipients routinely receive long courses of IV beta-lactam antibiotics to treat infection following conditioning therapy. 
  • Antibiotic-mediated damage of the gut microbiome in allogeneic HCT recipients may lead to adverse outcomes including CDI, VRE colonization and potentially fatal bacteremia and aGVHD. 
  • A previously completed placebo-controlled phase 2b clinical trial of 412 patients demonstrated SYN-004 protected the gut microbiome from antibiotic-mediated dysbiosis. 
  • Patients who received SYN-004 also demonstrated significantly better maintenance and recovery of the gut microbiome as well as lower incidences of new colonization by opportunistic and potentially pathogenic microorganisms such as VRE.

About the Company: Theriva Biologics

  • Theriva Biologics, is a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need. 
  • The company is advancing a new oncolytic adenovirus platform designed for intravenous (IV), intravitreal and antitumoral delivery to trigger tumor cell death, improve access of co-administered cancer therapies to the tumour.
  • It promotes a robust and sustained anti-tumour response by the patient’s immune system.

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