SYN-004 for Post-Bone Marrow Transplant Complications

Not currently recruiting at 1 trial location

Overseen By Kimberly Reske, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Synthetic Biologics Inc.

Must be taking: Beta-lactam antibiotics

Disqualifiers: Allergies, Other studies, Liver issues, others

Compensation: Varies

Number of Visits: 30

Duration: 7-9 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effects of a new oral treatment, SYN-004, for individuals who have undergone a bone marrow transplant and are experiencing post-procedure fevers. The researchers aim to determine if SYN-004 can protect the gut's natural bacteria while patients receive strong antibiotics. Individuals who have had a bone marrow transplant for certain blood cancers and can take an oral capsule might be suitable candidates for this study. As a Phase 1, Phase 2 trial, this research focuses on understanding how SYN-004 works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are currently enrolled in another clinical study or have taken an investigational drug recently, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that SYN-004 was safe in earlier studies. Patients who took SYN-004 as a pill generally tolerated it well, receiving a dose of 150 mg four times a day for up to 28 days. Importantly, there were no major reports of serious side effects. This suggests that SYN-004 is a safe option for individuals who have undergone a bone marrow transplant and are taking certain antibiotics. The purpose of using SYN-004 is to help maintain gut health, potentially reducing complications after a transplant. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

SYN-004 is unique because it targets the gut microbiome, aiming to prevent antibiotic-associated complications without disrupting beneficial gut bacteria. Unlike traditional treatments that often involve broad-spectrum antibiotics, which can lead to significant side effects and resistance issues, SYN-004 is designed to protect the gut flora while allowing antibiotics to fight infections. Researchers are particularly excited about SYN-004 because it offers a novel approach by breaking down certain antibiotics in the gut before they can harm the beneficial bacteria, potentially reducing complications like Clostridium difficile infections and antibiotic resistance, which are common concerns after bone marrow transplants.

What evidence suggests that SYN-004 might be an effective treatment for post-bone marrow transplant complications?

Research has shown that SYN-004, also known as ribaxamase, protects the gut by breaking down certain IV antibiotics in the digestive system. This process prevents these antibiotics from destroying beneficial gut bacteria, which is crucial for maintaining a healthy balance. Early findings suggest that by preserving the gut microbiome—the community of tiny organisms in the intestines—SYN-004 may enhance recovery for patients who have undergone bone marrow transplants. In this trial, participants will receive either SYN-004 or a placebo alongside IV antibiotics such as Meropenem, Piperacillin/Tazobactam, or Cefepime. Some early studies have indicated that maintaining this balance can lead to better recovery and fewer complications after the transplant. These potential protective effects on the gut make SYN-004 a promising option for improving patient health during this vulnerable period. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

Adults over 18 years old undergoing bone marrow transplant for blood disorders who can swallow a capsule and have consented to participate. They must not have severe kidney, heart, liver issues, lung function below 80%, certain infections or bleeding problems, be pregnant/breastfeeding, or allergic to the study drugs.

Inclusion Criteria

Participant is able to ingest the SYN-004 dosage form (size 0 hard capsule)

Participant provides written informed consent

I am 18 or older and will have a stem cell transplant for blood cancer or disorder.

Exclusion Criteria

Pregnant or breast feeding

I started on MER, PIP/TAZO, or FEP before joining this study.

You have had Clostridium difficile infection (CDI) in the past 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SYN-004 or placebo starting on day +1 after HCT until 72 hours after completion of IV antibiotics

7-9 days

Daily monitoring during treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

365 days

Weekly visits for the first 30 days, then periodic assessments up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• SYN-004

Trial Overview The trial is testing SYN-004's safety and its effects on gut bacteria in patients receiving bone marrow transplants who develop fevers treated with specific IV antibiotics. It also looks at how well SYN-004 enters the bloodstream and interacts with these antibiotics.

How Is the Trial Designed?

Group I: SYN-004 + IV Meropenem Active Control 1 Intervention

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)

Group II: SYN-004 + IV Piperacillin/Tazobactam Active Control 1 Intervention

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)

Group III: SYN-004 + Cefepime Active Control 1 Intervention

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)

Group IV: Placebo + IV Meropenem Placebo Group 1 Intervention

Placebo, oral administration, 4 times per day (q6h), beginning on day +1 after HCT until 72-hours after completion of IV Meropenem (MER)

Group V: Placebo + IV Piperacillin/Tazobactam Placebo Group 1 Intervention

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)

Group VI: Placebo + IV Cefepime Placebo Group 1 Intervention

Placebo, oral administration, 4 times per day (q6h), beginning on day +1 after HCT until 72-hours after completion of IV Cefepime (FEP)

Who Is Running the Clinical Trial?

Synthetic Biologics Inc.

Lead Sponsor

Trials

9

Recruited

720+

Theriva Biologics, Inc.

Lead Sponsor

Trials

9

Recruited

720+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Citations

1. therivabio.com therivabio.com/press_releases/theriva-biologics-announces-presentation-of-data-from-the-phase-1b-2a-clinical-trial-of-syn-004-ribaxamase-in-allogeneic-hematopoietic-cell-transplant-recipients/

Theriva Biologics Announces Presentation of Data from the ... 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 ...

2. biospace.com biospace.com/synthetic-biologics-announces-first-patient-dosed-in-phase-1b-2a-clinical-trial-of-syn-004-ribaxamase-in-allogeneic-hematopoietic-cell-transplant-recipients

Synthetic Biologics Announces First Patient Dosed in ... SYN-004 (ribaxamase) is an oral prophylactic therapy designed to degrade certain IV beta-lactam antibiotics within the GI tract and maintain the ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8327718/

The post-hematopoietic cell transplantation microbiome Results from the first, predominantly single-arm trials have demonstrated potential for microbiota-modulating therapies to improve transplant outcomes (e.g., ...

4. therivabio.com therivabio.com/press_releases/theriva-biologics-announces-presentation-of-safety-and-pharmacokinetic-data-from-cohort-1-of-the-phase-1b-2a-clinical-trial-of-syn-004-ribaxamase-in-allogeneic-hematopoietic-cell-transplant-recipien/

Theriva™ Biologics Announces Presentation of Safety and ... SYN-004 (ribaxamase) is an oral prophylactic therapy designed to degrade certain IV beta-lactam antibiotics within the GI tract and maintain the ...

5. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK12966/

Complications of Hematopoietic Transplantation - NCBI - NIH Late complications of hematopoietic transplantation include delayed effects of high-dose therapy, indolent infections, transfusion-related complications, and ...

6. therivabio.com therivabio.com/press_releases/theriva-biologics-announces-positive-outcome-of-data-and-safety-monitoring-committee-dsmc-review-in-phase-1b-2a-clinical-trial-of-syn-004-ribaxamase-in-allogeneic-hematopoietic-cell-trans/

Theriva™ Biologics Announces Positive Outcome of Data ... 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 ...

7. finance.yahoo.com finance.yahoo.com/news/nano-cap-theriva-biologics-investigational-144546836.html

Nano-Cap Theriva Biologics' Investigational Drug For ... Nano-Cap Theriva Biologics' Investigational Drug For Transplant-Related Complication Shows Safety In Bone Marrow Transplant Patients ...

8. ashpublications.org ashpublications.org/hematology/article/2023/1/141/506430/Posttransplant-complications-in-patients-with

Posttransplant complications in patients with marrow failure ... The most common IBMFS include Fanconi anemia, Shwachman-Diamond syndrome, Diamond-Blackfan anemia, and telomere biology disorders/ dyskeratosis ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10821161/

Post-Transplant Complications in Patients Undergoing ... The main purpose of this research is to analyze the differences in the appearance of post-transplant complications between patients having ...