SYN-004 Safety and Tolerability in Allo-HCT Subjects

NCT04692181 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: SB-1-004-006
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Study Objectives:

1. 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. 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. 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. 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

Conditions

Acute Graft-Versus-Host Reaction Following Bone Marrow Transplant; Prevention of CDI in Adult Patients Being Treated With IV Beta-lactam Antibiotics

Outcome Measures

Primary Outcomes (6)

• SYN-004 systemic absorption

  Assess potential SYN-004 systemic absorption (if any) by measuring SYN-004 plasma concentrations

  No more than 28 days

• Systemic antibiotic 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

  Up to 8 hours after IV administration of antibiotic

• Bacteremia

  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

  Daily during treatment, and weekly until 30 days after discontinuation of SYN-004 or Placebo

• Bacterial intestinal infections

  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

  Daily during treatment, and weekly until 30 days after discontinuation of SYN-004 or Placebo

• Grade 3 or 4 adverse events

  Assess tolerability of SYN-004 and grade 3 or 4 adverse events up to 30 days after the last dose of SYN-004

  Up to 30 days after the last dose of SYN-004 or Placebo

• Overall survival

  Overall survival at 30 days after last dose of SYN-004

  Up to 30 days after the last dose of SYN-004 or Placebo

Secondary Outcomes (4)

• First line failure of PIP/TAZO or FEP

  Up to 30 days after the last dose of SYN-004 or Placebo

• Gut microbiome protection

  Up to 30 days after the last dose of SYN-004 or Placebo, and up to 180 days after HCT

• Urine concentrations of 3-indoxyl sulfate

  Up to 30 days after the last dose of SYN-004 or Placebo, and up to 180 days after HCT

• Impact on immunosuppressant dosing

  Up to 30 days after the last dose of SYN-004 or Placebo, and up to 180 days after HCT

Other Outcomes (10)

• Long-term overall survival

  180 and 365 days after HCT

• Relapse free survival

  180 and 365 days after HCT

• Incidence of aGVHD

  30 days after last dose of SYN-004 or Placebo, and 180 days after HCT

Study Arms (6)

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)

Biological: SYN-004, Ribaxamase or Placebo

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)

Biological: SYN-004, Ribaxamase or Placebo

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)

Biological: SYN-004, Ribaxamase or Placebo

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)

Biological: SYN-004, Ribaxamase or Placebo

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)

Biological: SYN-004, Ribaxamase or Placebo

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)

Biological: SYN-004, Ribaxamase or Placebo

Interventions

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

Placebo + IV Cefepime; Placebo + IV Meropenem; Placebo + IV Piperacillin/Tazobactam; SYN-004 + Cefepime; SYN-004 + IV Meropenem; SYN-004 + IV Piperacillin/Tazobactam

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant provides written informed consent.
• Male or female patients ≥18 years undergoing myeloablative allo-HCT for a hematologic malignancy or myeloproliferative disorder.
• Participant is able to ingest the SYN-004 dosage form (size 0 hard capsule).

You may not qualify if:

• Allergy(ies) to MER, PIP, TAZO, or FEP.
• History of allergy to SYN-004 or its components.
• Admitted for HCT and started on MER, PIP/TAZO, or FEP prior to enrollment in the present study.
• Currently enrolled in another interventional clinical study or received an investigational drug or device within 30 days or within a time period consistent with a washout period of 5 half-lives before signing the Informed Consent Form, whichever is longer.
• Recipients of umbilical cord blood transplantation.
• Underlying condition requiring HCT is not in remission (per International Working Group definitions), except for myelodysplastic syndrome and lymphoma, as long as these conditions are chemotherapy responsive.
• Creatinine clearance \<60 mL/min/1.73 m² by Cockroft-Gault calculation.
• Cardiac ejection fraction \<50%.
• Cirrhosis, bilirubin \>1.5x upper limit of normal, or AST/ALT \>2.5x upper limit of normal.
• History of veno-occlusive disease (VOD) or hepatic sinusoidal obstructive syndrome (SOS).
• DLCO and/or FEV1 ≤80% of normal.
• Chronic HIV or HBV infection.
• Invasive fungal infection not responding to treatment at time of HCT.
• Known active bacterial or viral infection at time of HCT.
• CDI in the preceding 6 months.

Sponsors & Collaborators

• Theriva Biologics, Inc.: lead
• Washington University School of Medicine: collaborator

Study Sites (1)

Washington University

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Interventions

SYN-004

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blinding by randomization schedule
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2020
• First Posted: December 31, 2020
• Study Start: February 15, 2021
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2030
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)