A Phase 1/2 interventional study of SYN-004, Ribaxamase or Placebo in Acute Graft-Versus-Host Reaction Following Bone Marrow Transplant and Prevention of CDI in Adult Patients Being Treated With IV Beta-lactam Antibiotics, sponsored by Theriva Biologics, Inc.. Active, not recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-17.
Sponsored by Theriva Biologics, Inc. · Phase 1/2, Interventional, and Prevention
Study Objectives:
Study Design:
This is a single-center, placebo controlled, double blinded Phase 1b/2a study to assess the safety, tolerability and potential efficacy of orally administered SYN-004 in adult allo-HCT recipients. Participants will be randomized 2:1 to SYN-004 or placebo in blocks of three, stratified in three cohorts based on study assigned antibiotic (MER, piperacillin/tazobactam [PIP/TAZO], FEP) to be administered if the treating clinicians determine initiation of broad-spectrum antibiotics is indicated. As such, there will be six groups based on antibiotic cohort and randomized assignment of study drug:
Group 1: Placebo + IV MER (n=4) (MER control). Group 2: SYN-004 + IV MER (n=8) (MER treatment). Group 3: Placebo + IV PIP/TAZO (n=4) (PIP/TAZO control). Group 4: SYN-004 + IV PIP/TAZO (n=8) (PIP/TAZO treatment). Group 5: Placebo + IV FEP (n=4) (FEP control). Group 6: SYN-004 + IV FEP (n=8) (FEP treatment). Study-assigned antibiotics will be dosed as follows (adjusted for renal function as needed): MER 1 gram every 8 hours, PIP/TAZO 4.5 grams every 6 hours, FEP 1 gram every 8 hours. SYN-004 treated participants (Groups 2, 4 and 6) will be compared to control participants who receive placebo (Groups 1, 3 and 5, respectively). The study will be conducted in stages, commencing with Groups 1 and 2 who will be assigned to receive MER if antibiotics are indicated. MER is the first cohort because anti-infective efficacy of MER is not anticipated to be affected if SYN-004 is absorbed systemically. Accrual for Groups 3 and 4 (PIP/TAZO cohort) will begin only after review of the data from Groups 1 and 2 by the Data and Safety Monitoring Committee (DSMC) and agreement to proceed. PIP/TAZO is the next cohort because TAZO is a beta-lactamase inhibitor. As such, in the unlikely event of SYN-004 systemic absorption, TAZO systemic concentrations should be sufficient to inhibit any absorbed SYN-004. Accrual for the FEP cohort will begin after approval by the DSMC's review of results from groups 3 and 4.
Patients planned to receive an allo-HCT will be eligible for enrollment in the study and can be enrolled anytime from when it is known they will undergo HCT until day +1 after HCT (day of study drug start). Written informed consent will be obtained by all patients. To count towards the enrollment goal of 36 participants, a study participant must receive at least 80% of scheduled study drug doses from initiation of study assigned antibiotics through the second antibiotic pharmacokinetic assessment (7-9 days of concomitant study drug and study assigned antibiotic). Additional participants will be enrolled to replace participants who do not meet criteria to count towards the goal study enrollment until the goal enrollment is achieved.
This Phase 1b/2a study will use the SYN-004 dosing regimen (150 mg, PO, q6h) used in previous Phase 1 and Phase 2 clinical trials in healthy volunteers and patents with LRTIs. The first dose of study drug will be administered at day +1 after HCT and will be continued until Criteria for Discontinuation of Study Drug are met.
The study will consist of two periods: the Treatment Period and the Follow-up Period.
The Follow-up Period begins after cessation of study drug dosing and is split into three parts:
All participants will be evaluated as outlined in the Schedule of Assessments. At predetermined points during the study as outlined in the SOA, blood samples, urine samples, fecal swabs, and fecal samples will be collected for the indicated analyses.
Theriva Biologics, Inc. is the lead sponsor of 8 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
FEV1
From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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, 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, 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, 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, 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, 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
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
SYN-004 systemic absorption
Assess potential SYN-004 systemic absorption (if any) by measuring SYN-004 plasma concentrations
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Up to 30 days after the last dose of SYN-004 or Placebo
First line failure of PIP/TAZO or FEP
Assess the number of study participants who fail first line PIP/TAZO or FEP therapy and require second line therapy with another antibiotic
Time frame: Up to 30 days after the last dose of SYN-004 or Placebo
Gut microbiome protection
Assess the ability of SYN-004 to protect the gut microbiome (defined by alterations from baseline in bacterial community composition, metabolic potential of the microbiome, and antibiotic resistome) in study participants treated with PIP/TAZO or FEP, and confirm lack of protection in study participants treated with MER at up to 30 days after last dose of SYN-004 (and up to 180 days after HCT)
Time frame: 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
Assess urine concentrations of 3-indoxyl sulfate as a biomarker of fecal levels of Clostridium and Enterococcus species up to 30 days after last dose of SYN-004 (and 180 days after HCT)
Time frame: Up to 30 days after the last dose of SYN-004 or Placebo, and up to 180 days after HCT
Impact on immunosuppressant dosing
Assess impact of SYN-004 on immunosuppressant dosing and levels obtained through routine care up to 30 days after last dose of SYN-004 (and 180 days after HCT)
Time frame: Up to 30 days after the last dose of SYN-004 or Placebo, and up to 180 days after HCT
Long-term overall survival
Overall survival at 180 and 365 days after HCT
Time frame: 180 and 365 days after HCT
Relapse free survival
Relapse free survival at 30 days after last dose of SYN-004 (and 180 and 365 days after HCT)
Time frame: 180 and 365 days after HCT
Incidence of aGVHD
Incidence of aGVHD at 30 days after last dose of SYN-004 (and 180 days after HCT)
Time frame: 30 days after last dose of SYN-004 or Placebo, and 180 days after HCT
GVHD and relapse free survival
GVHD and relapse free survival at 30 days after last dose of SYN-004 (and 180 and 365 days after HCT)
Time frame: 30 days after last dose of SYN-004 or Placebo, and 180 and 365 days after HCT
Incidence of CDI
Assess the incidence of CDI up to 30 days after last dose of SYN-004 (and up to 180 days after HCT)
Time frame: 30 days after last dose of SYN-004 or Placebo, and up to 180 days after HCT
Incidence of MDRO bacteremia and Candidemia
Assess the incidence of MDRO bacteremia and Candidemia up to 30 days after last dose of SYN-004 (and up to 180 days after HCT)
Time frame: 30 days after last dose of SYN-004 or Placebo, and up to 180 days after HCT
Incidence of chronic GVHD
Assess incidence of chronic GVHD at 180 days and 1 year after HCT
Time frame: 180 days and 1 year after HCT
New stool colonization with MDRO and Candida species
Assess the rate of new stool colonization with MDRO and Candida species up to 30 days after last dose of SYN-004 (and up to 180 days after HCT)
Time frame: Up to 30 days after last dose of SYN-004 or Placebo, and up to 180 days after HCT
Microbiome domination due to MDRO
Assess microbiome domination (defined as ≥30% of all bacterial species present in the intestinal microbiome) due to MDRO up to 30 days after last dose of SYN-004 (and 180 days after HCT)
Time frame: Up to 30 days after last dose of SYN-004 or Placebo, and up to 180 days after HCT
New colonization with C. difficile
Assess new colonization with C. difficile
Time frame: Up to 30 days after last dose of SYN-004 or Placebo, and up to 180 days after HCT
Plan to share: No
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Theriva Biologics, Inc.