D-PLEX for Surgical Site Infection

(D-PLEX312 Trial)

No longer recruiting at 90 trial locations

Overseen By Shifra Fain-Shmueli

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: PolyPid Ltd.

Must not be taking: Antibiotics, Anticancer, Investigational drugs, others

Disqualifiers: Active infection, Recent surgery, Allergies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called D-PLEX, a type of antibiotic therapy, to determine if it can prevent infections after abdominal surgery. Participants will receive either D-PLEX with the usual care or just the usual care to compare outcomes. The goal is to assess whether D-PLEX is safe and effective in reducing infection risks. Individuals who have had planned colorectal surgery with a large abdominal incision and are stable before surgery might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, providing an opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have taken certain antibiotics or anti-cancer treatments recently. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that D-PLEX is likely to be safe for humans?

Research shows that D-PLEX is generally safe for patients. Specifically, it has proven safe for immediate use in surgeries involving contaminated bones, helping to reduce infection risks without major complications. While detailed information about side effects in abdominal surgeries is lacking, its use in other surgeries suggests a favorable safety profile. As this trial is in a late stage, D-PLEX likely demonstrated a good safety record in earlier studies, increasing the likelihood of safety for participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

D-PLEX is unique because it acts as an adjunct to the standard prophylactic antibiotic treatments, specifically targeting the prevention of surgical site infections. Unlike traditional antibiotics that circulate throughout the body, D-PLEX is applied directly at the surgical site, allowing for a sustained release of the antibiotic locally. This direct delivery method can potentially reduce the risk of systemic side effects and improve the effectiveness of infection prevention right where it's needed most. Researchers are excited about D-PLEX because it could represent a significant advance in reducing post-surgical infections with a more focused approach.

What evidence suggests that D-PLEX might be an effective treatment for surgical site infection?

Research has shown that D-PLEX, which participants in this trial may receive, can greatly reduce infections at the surgery site after abdominal surgery. In one study, using D-PLEX with standard care led to 58% fewer infections compared to standard care alone. Specifically, fewer patients developed infections when D-PLEX was part of their treatment. The treatment delivers antibiotics directly to the surgery area, preventing bacteria from causing infections. Early results are promising, suggesting that D-PLEX could enhance current methods for preventing infections. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults over 18, undergoing elective colorectal surgery with a large incision, who are stable before the operation and expected to live at least 60 days after. Women must not be pregnant and agree to birth control. Excludes those with recent abdominal surgeries or infections, severe allergies, liver/kidney issues, or active cancer treatments.

Inclusion Criteria

My blood pressure, heart rate, and temperature are within safe ranges.

I am a woman who can have children and have a negative pregnancy test.

Subjects who sign the written Informed Consent Form.

Exclusion Criteria

I have had certain sterilization surgeries or procedures on my small bowel or gallbladder, with approval from the trial sponsor.

I had radiation for colorectal cancer in my abdomen or pelvis before planned surgery.

I was diagnosed with a stroke less than 6 months ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Treatment

D-PLEX is applied during the surgery at the final stage of incision closure

Immediate

1 visit (in-person)

Follow-up

Participants are monitored for safety and incisional wound assessment, including blood tests and physician's assessment

8 weeks

5 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• D-PLEX

Trial Overview This Phase III trial is testing D-PLEX's safety and effectiveness in preventing infection after abdominal surgery compared to standard care alone. Participants will be randomly assigned to receive either D-PLEX plus standard care or just standard care in a double-blind setup.

How Is the Trial Designed?

Group I: Standard of Care Experimental Treatment 1 Intervention

The SoC for prophylactic antibiotic treatment is based on international guidelines

Group II: D-PLEX+SoC Experimental Treatment 2 Interventions

D-PLEX is provided to suitable and willing study subjects as an adjunct to the SoC treatment

Who Is Running the Clinical Trial?

PolyPid Ltd.

Lead Sponsor

Trials

7

Recruited

1,900+

Published Research Related to This Trial

In a study of 81 cardiac surgery patients, D-PLEX100 (D-PLEX) demonstrated a strong safety profile with no serious adverse events related to sternal wound infections (SWI), and it effectively prevented SWI in the treatment group (0/60) compared to one case in the control group (1/21).

D-PLEX provided localized, prolonged release of the antibiotic doxycycline, resulting in significantly lower plasma levels compared to oral administration, suggesting a targeted approach that minimizes systemic exposure while effectively preventing infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local prolonged release of antibiotic for prevention of sternal wound infections postcardiac surgery-A novel technology. Kachel, E., Moshkovitz, Y., Sternik, L., et al.[2020]

The biodegradable doxycycline/polymer-lipid encapsulation matrix (D-PLEX100) was found to be safe in a study involving Yucatan miniature swine, with no systemic toxicity or migration from the surgical site observed over a 6-month follow-up period.

D-PLEX100 demonstrated effective controlled release of doxycycline, with detectable drug levels in the plasma for up to 15 days, supporting its potential use in preventing surgical site infections in abdominal surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

D-PLEX100 in an Abdominal Surgery Incision Model in Miniature Swine: Safety Study. Ramot, Y., Nedvetzki, S., Rosenfeld, S., et al.[2021]

D-PLEX100, a local antibiotic-releasing paste, demonstrated significant efficacy in reducing surgical site infections (SSIs) in animal models, achieving over a 6.5 Log10 reduction in bacterial loads, including resistant strains like MRSA.

In a clinical trial involving colorectal surgery patients, D-PLEX significantly lowered the SSI rate to 28% compared to 94% in the standard care group, while also showing lower antibiotic resistance rates, indicating its potential as a safe and effective prophylactic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent antibacterial activity in surgical wounds with local administration of D-PLEX100. Emanuel, N., Kozloski, GA., Nedvetzki, S., et al.[2023]

In a Phase 2 clinical trial involving 202 patients undergoing elective colorectal surgery, the use of D-PLEX100 in addition to standard care resulted in a 64% relative risk reduction in surgical site infections (SSIs) compared to standard care alone, with an SSI rate of 8% in the D-PLEX100 group versus 22% in the control group.

The application of D-PLEX100 was found to be safe, as there were no significant differences in treatment-emergent adverse events between the D-PLEX100 group and the standard care group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, randomized assessment of a novel, local antibiotic releasing platform for the prevention of superficial and deep surgical site infections. Zmora, O., Stark, Y., Belotserkovsky, O., et al.[2023]

D-PLEX100, a doxycycline-releasing product designed to prevent surgical site infections, showed no systemic safety concerns or local toxicity in juvenile Yucatan miniature swine over a 9-month observation period, supporting its safety for future pediatric trials.

The study demonstrated that D-PLEX was fully resorbed within 3 months and did not adversely affect the healing of surgical incisions, indicating its potential efficacy and safety for use in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical In-Vivo Safety and Toxicokinetics of D-PLEX100 in an Abdominal Surgery Incision Model in Juvenile Miniature Swine. Ramot, Y., Nyska, A., Dvir, M., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04411199

Study Details | NCT04411199 | D-PLEX 312 - Safety and ... To assess the anti-infective efficacy of D-PLEX over a period of 30 days post operation, by preventing surgical site infection (SSI), defined as superficial and ...

2. investors.polypid.com investors.polypid.com/news-releases/news-release-details/polypid-announces-positive-topline-results-phase-3-shield-ii

PolyPid Announces Positive Topline Results from Phase 3 ... The trial successfully met all key secondary efficacy endpoints, including a 58% reduction in the rate of surgical site infections (“SSI”) in ...

3. clinicaltrial.be clinicaltrial.be/en/details/55519?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Safety and Efficacy of D-PLEX in the Prevent... To assess the anti-infective efficacy of D-PLEX over a period of 30 days post operation, by preventing surgical site infection (SSI), defined as ...

4. polypid.com polypid.com/pipeline/bonypid-1000/

D-PLEX1000 D-PLEX 1000 is designed for filling bone voids, providing effective eradication of bone infection caused by doxycycline-sensitive microorganism around the ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36567225/

Reduction in surgical site infections by localized ... D-PLEX 100 reduces the incidence of SSIs beyond benefits associated with SOC treatment alone and including patients with ≥2 risk factors.

6. polypid.com polypid.com/pipeline/clinical-trials-phase-3/

CLINICAL TRIALS D-PLEX100 – 311 – ( NCT04233424 ) – Abdominal / Colorectal surgery. Efficacy and Safety of D-PLEX in the Prevention of Abdominal Surgery Incision Infection ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10784838/

Antimicrobial approach of abdominal post-surgical infections The purpose of this review is to provide a practical update on the latest available literature on SSIs, focusing on causative pathogens and treatment.