Phase III, Prospective, Multinational, Multicenter, Randomized, Controlled, Two-arm, Double Blind Study to Assess Efficacy and Safety of D-PLEX Administered Concomitantly with the Standard of Care (SoC), Compared to a SoC Treated Control Arm, in Prevention of Post Abdominal Surgery Incisional Infection.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Polypid Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

17 Mar 2021 → 10 May 2025

Decision date (initial)

2024-02-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-509698-21-00

EudraCT number

2020-003617-36

ClinicalTrials.gov

NCT04411199

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Prophylaxis, Safety, Efficacy

To assess the anti-infective efficacy of D-PLEX administered concomitantly with the Standard of Care (SoC) over a period of 30 days post operation, by preventing surgical site infection (SSI), defined as superficial and/or deep infection, in the target incision, compared to the SoC treated control arm and to assess the safety of D-PLEX administered concomitantly with the Standard of Care (SoC).

Secondary objectives 3

1. Infection rate as measured by the proportion of subjects with at least one abdominal target incisional infection event, occurring within 30 days post abdominal (index) surgery and determined by a blinded and independent adjudication committee, in the population of subjects with target incision length >20cm.
2. Infection rate as measured by the proportion of subjects with at least one abdominal target incisional infection event, occurring within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee, in the overall study population (incision ≥7cm). All-cause mortality and re-interventions through the abdominal incision (target) within 30 days post index surgery will be analysed as treatment failure.
3. Number (percent) of subjects with at least 1 score of ASEPSIS >20, within 30 days post abdominal (index) surgery (population of subjects with target incision length >20cm).

Conditions and MedDRA coding

Prevention of post abdominal surgery incisional infection.

Regulatory references

Scientific advice from competent authorities

Health Products Regulatory Authority, Swedish Medical Products Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Subjects undergoing an elective colorectal surgery involving resection, with or without a stoma formation, that includes at least 1 abdominal incision (target incision) that is >20cm.
2. Subjects are preoperative hemodynamically stable (BP≤180/12 and ≥90/60 mmHg, and HR≤120 and ≥60 bpm, and temperature ≤37.5°C and ≥35.5°C).
3. Male or non-pregnant female.
4. Female of child-bearing potential should have a negative pregnancy test (serum or urine dipstick) prior to index procedure. Note: All female subjects of child-bearing potential must agree to use a highly effective method of contraception consistently and correctly for the duration of the study (see Section 8.6 – CONTRACEPTIVE METHODS).
5. Subjects’ age 18 years old and above at screening.
6. Subjects who sign the written Informed Consent Form.
7. Subjects who are willing and able to participate and meet all study requirements.
8. Survival expectancy of at least 60 days post randomization.

Exclusion criteria 23

1. Subjects with suspected/diagnosed intestinal perforation, intra-abdominal abscess, or any emergency/urgent colorectal surgery with acute intestinal obstruction (for example toxic colitis, ileus/subileus, megacolon, diverticulitis, volvulus, etc).
2. Subjects who underwent an intra-abdominal surgery within the last 6 months prior to randomization.
3. Subjects with an preoperative infection or who are receiving any antibiotic therapy in the past one week prior to randomization, excluding pre-operative prophylaxisor or antibiotics for the treatment of the disease that is the indication for surgery.
4. Subjects undergoing concomitant major procedures in addition to the colorectal resection. Female sterilization surgeries (i.e. salpingo-oophorectomy etc.), involvement of a small bowel procedure or cholecystectomy may be allowed, pending an advanced consultation and approval from the Sponsor.
5. Subject who received any anti-cancer treatment within the last 4 weeks of surgery
6. Subjects who received abdomen and/or pelvis area radiotherapy for colorectal cancer within the last 4 weeks of the planned abdominal surgery.
7. Subjects who received oral or IV Doxycycline/Tetracycline family antibiotic during the past 4 weeks prior to randomization.
8. Subjects with known allergy to Doxycycline and/or to the tetracycline family of drugs or to the D-PLEX's excipients.
9. Subjects with known allergies to more than 3 substances (an allergy questionnaire will be completed during the screening process).
10. Subjects with history of severe allergic reaction to any substance, having required treatment with intravenous steroids/intramuscular epinephrine, or who in the opinion of the PI is at high risk of developing severe allergic reactions.
11. Subjects with End Stage Renal Disease (ESRD/CKD stage 5).
12. Subjects with severe hepatic impairment.
13. Subjects with chronic urticaria.
14. Subjects diagnosed with CVA within the past 6 months prior to randomization.
15. Subjects that undergone any abdominal surgery and current planned index surgery involves re-opening the scar of a prior abdominal surgery performed within the last 3 years.
16. Any subject with an active malignancy or with malignancy that has not been in complete clinical remission and without maintenance chemo or immunotherapy for at least 3 years. Excluding: Subjects with potentially resectable non-metastatic colorectal cancer that is the reason for the index surgery. Subjects with carcinoma in situ (or other cancer "in situ = Stage 0"), or squamous cell carcinoma of the skin, or basal cell carcinoma of the skin. Subjects with any additional non-violent tumor that does not require treatment 4 weeks prior to the surgery, and throughout the entire study duration.
17. Subjects with other concurrent severe and/or uncontrolled medical condition.
18. Psychiatric or any other disorder that compromises the ability to provide Informed Consent Form for participation in this study.
19. Chronic alcoholic or drug abuse subjects.
20. Pregnant or breast-feeding women or women of child-bearing potential who refuse or are prohibited of using an effective contraceptive method of birth control throughout study participation, including the safety follow-up period.
21. Subjects who received any investigational drug within 30 days or 5 half-lives prior to randomization to the study (whichever is longer) and through the study.
22. Subjects participating in any other interventional studies.
23. Subjects who in the opinion of Investigator are not eligible to participate in the study and/or to comply with protocol requirements (e.g., due to a cognitive or medical condition).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Infection rate as measured by the proportion of subjects with at least one abdominal target incisional infection event, occurring within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee, in the study population with longer incision (>20cm). [abdominal incisional infection is defined as Deep Incisional Surgical Site Infection (DSSI) and/or Superficial Incisional Surgical Site Infection (SSSI)].

Secondary endpoints 16

1. Infection rate as measured by the proportion of subjects with at least one abdominal target incisional infection event, occurring within 30 days post abdominal (index) surgery and determined by a blinded and independent adjudication committee, in the population of subjects with target incision length >20cm.
2. Infection rate as measured by the proportion of subjects with at least one abdominal target incisional infection event, occurring within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee, in the overall study population (incision ≥7cm). All-cause mortality and re-interventions through the abdominal incision (target) within 30 days post index surgery will be analysed as treatment failure.
3. Number (percent) of subjects with at least 1 score of ASEPSIS > 20, within 30 days post abdominal (index) surgery (population of subjects with target incision length >20cm).
4. Additional endpoints (population of subjects with target incision length >20cm): Incidence of SSSI during 30 days post index surgery.
5. Additional endpoints (population of subjects with target incision length >20cm): Incidence of DSSI during 30 days post index surgery.
6. Additional endpoints (population of subjects with target incision length >20cm): All-cause mortality rate within 30 days post randomization.
7. Additional endpoints (population of subjects with target incision length >20cm): All-cause mortality rate within 60 days post randomization.
8. Additional endpoints (population of subjects with target incision length >20cm): Time to adjudicated SSI during 30 days post index surgery.
9. Additional endpoints (population of subjects with target incision length >20cm): Number (percent) of subjects re-admitted during 30 days post index surgery (for any reason) that have experienced adjudicated SSI during this re-admission.
10. Additional endpoints (population of subjects with target incision length >20cm): Number (percent) of subjects who experienced at least 1 surgical re-intervention due to adjudicated SSIs during 30 days post index surgery.
11. SSI related Additional Endpoints: Number (percent) of subjects with adjudicated SSI where at least one Doxycycline-resistant bacteria have grown in bacteriology tests.
12. SSI related Additional Endpoints: Number (percent) of Doxycycline-resistant bacteria out of all bacteria that were cultured during bacteriology test from subjects with adjudicated SSI.
13. SSI related Additional Endpoints: Number (percent) of subjects who experienced adjudicated SSI during 30 days post index surgery that were treated by IV antibiotic.
14. SSI related Additional Endpoints: Number of IV antibiotic treatment days, administered to subjects who experience adjudicated SSI during 30 days post index surgery.
15. SSI related Additional Endpoints: Average of subjects’ cumulative ASEPSIS assessment score (AUC) for subjects with adjudicated SSI during 30 days.
16. SSI related Additional Endpoints: Number (percent) of subjects with at least 1 score of ASEPSIS > 20 in subject with adjudicated SSI within 30 days post abdominal (index) surgery.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Polypid Ltd.

Sponsor organisation

Polypid Ltd.

Address

18 Ha-Sivim

City

Petakh Tikva

Postcode

4959376

Country

Israel

Scientific contact point

Organisation

Polypid Ltd.

Contact name

Dalit Hazan

Public contact point

Organisation

Polypid Ltd.

Contact name

Dalit Hazan

Third parties 7

Locations

7 EU/EEA countries · 32 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 28 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications