Acute Graft-Versus-Host Reaction Following Bone Marrow TransplantPhase 1/2NCT04692181
SYN-004 Safety and Tolerability in Allo-HCT Subjects
A Phase 1/2 study of Acute Graft-Versus-Host Reaction Following Bone Marrow Transplant and Prevention of CDI in Adult Patients Being Treated With IV Beta-lactam Antibiotics, run by Theriva Biologics, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Graft-Versus-Host Reaction Following Bone Marrow Transplant, Prevention of CDI in Adult Patients Being Treated With IV Beta-lactam Antibiotics
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Feb 2021to 30 Sep 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
- Unable to comply with study protocol as determined by primary investigator.
- Active gastrointestinal (GI) bleeding at time of HCT.
- Prior colectomy or short gut syndrome.
- Pregnant or breast feeding.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1b/2a Evaluation of the Safety and Tolerability of SYN-004 in Adult Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) Recipients
Study Objectives:
- 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).
- 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.
- To evaluate potential protective effects of SYN-004 on the intestinal microbiome of allo-HCT recipients treated with IV MER, PIP/TAZO or FEP.
- 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
Read the detailed description
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 Treatment Period will be defined as the time from first dose of study drug until the last dose. For participants who do not meet criteria for early discontinuation, study drug will be continued for 72 hours after last dose of MER, PIP/TAZO, or FEP.
- The Follow-up Period begins after cessation of study drug dosing and is split into three parts:
- Part A: up to 30 days after study drug was discontinued
- Part B: from end of Part A to day +180 after HCT
- Part C: from end of Part B to day +365 after HCT Patients enrolled in the study will receive conditioning and HCT according to their treatment plan. Fever and time of antibiotic start will be defined per local standard of care of patients. Cessation of antibiotic therapy and/or changes to antibiotic therapy will be at the discretion of the treating physician.
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.
- Conditions
- Acute Graft-Versus-Host Reaction Following Bone Marrow Transplant, Prevention of CDI in Adult Patients Being Treated With IV Beta-lactam Antibiotics
- Being tested
- SYN-004, Ribaxamase or Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SYN-004, Ribaxamase or PlaceboBiological
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 group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: 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) Receives: 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) Receives: 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) Receives: 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) Receives: Biological: SYN-004, Ribaxamase or Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
SYN-004 systemic absorption
Assess potential SYN-004 systemic absorption (if any) by measuring SYN-004 plasma concentrations
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Up to 30 days after the last dose of SYN-004 or Placebo
Secondary outcomes (4)
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
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Up to 30 days after the last dose of SYN-004 or Placebo, and up to 180 days after HCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2020
- Study start15 Feb 2021
- Primary completion30 Sep 2029 (estimated)
- Study completion30 Sep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Graft-Versus-Host Reaction Following Bone Marrow TransplantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Theriva Biologics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Washington University School of Medicine
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04692181
- Sponsor's protocol ID
- SB-1-004-006
- Status last verified
- Mar 2026
- First submitted
- 28 Dec 2020
- Last updated
- 17 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1b/2a Evaluation of the Safety and Tolerability of SYN-004 in Adult Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) Recipients
- ClinicalTrials.gov ID
- NCT04692181
- Acronym / sponsor ID
- SB-1-004-006
- Conditions
- Acute Graft-Versus-Host Reaction Following Bone Marrow Transplant, Prevention of CDI in Adult Patients Being Treated With IV Beta-lactam Antibiotics
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Theriva Biologics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Washington University School of Medicine
- Study start
- 15 Feb 2021 (actual)
- Primary completion
- 30 Sep 2029 (estimated)
- Study completion
- 30 Sep 2030 (estimated)
- First posted
- 31 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study Objectives:
- 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).
- 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.
- To evaluate potential protective effects of SYN-004 on the intestinal microbiome of allo-HCT recipients treated with IV MER, PIP/TAZO or FEP.
- 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
Detailed description
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 Treatment Period will be defined as the time from first dose of study drug until the last dose. For participants who do not meet criteria for early discontinuation, study drug will be continued for 72 hours after last dose of MER, PIP/TAZO, or FEP.
- The Follow-up Period begins after cessation of study drug dosing and is split into three parts:
- Part A: up to 30 days after study drug was discontinued
- Part B: from end of Part A to day +180 after HCT
- Part C: from end of Part B to day +365 after HCT Patients enrolled in the study will receive conditioning and HCT according to their treatment plan. Fever and time of antibiotic start will be defined per local standard of care of patients. Cessation of antibiotic therapy and/or changes to antibiotic therapy will be at the discretion of the treating physician.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Placebo + IV Meropenem | Placebo comparator | Biological: SYN-004, Ribaxamase or PlaceboPlacebo, 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 | Biological: SYN-004, Ribaxamase or PlaceboSYN-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 | Biological: SYN-004, Ribaxamase or PlaceboPlacebo, 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 | Biological: SYN-004, Ribaxamase or PlaceboSYN-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 | Biological: SYN-004, Ribaxamase or PlaceboPlacebo, 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 | Biological: SYN-004, Ribaxamase or PlaceboSYN-004, oral administration, 150mg, 4 times per day (q6h), beginning on day +1 after HCT until 72-hours after completion of IV Cefepime (FEP) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SYN-004, Ribaxamase or PlaceboSYN-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 | Biological | Placebo + IV Cefepime, Placebo + IV Meropenem, Placebo + IV Piperacillin/Tazobactam, SYN-004 + Cefepime, SYN-004 + IV Meropenem, SYN-004 + IV Piperacillin/Tazobactam |
Primary outcome
SYN-004 systemic absorption
Time frame: No more than 28 days
Assess potential SYN-004 systemic absorption (if any) by measuring SYN-004 plasma concentrations
Systemic antibiotic concentrations
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Up to 30 days after the last dose of SYN-004 or Placebo
Overall survival at 30 days after last dose of SYN-004
4 secondary outcomes
First line failure of PIP/TAZO or FEP
Time frame: Up to 30 days after the last dose of SYN-004 or Placebo
Gut microbiome protection
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
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
Time frame: Up to 30 days after the last dose of SYN-004 or Placebo, and up to 180 days after HCT
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2026.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study of Acute Graft-Versus-Host Reaction Following Bone Marrow Transplant and Prevention of CDI in Adult Patients Being Treated With IV Beta-lactam Antibiotics, run by Theriva Biologics, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 17 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
SYN-004 systemic absorption (time frame: No more than 28 days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2026.