Clinical Trials Register

Summary
EudraCT Number:	2020-002325-28
Sponsor's Protocol Code Number:	D-PLEX311
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-09-02
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2020-002325-28

A.3

Full title of the trial

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

Prospektivní, multinárodní, multicentrická, randomizovaná, kontrolovaná, dvojitě zaslepená studie fáze III s dvěma rameny k vyhodnocení účinnosti a bezpečnosti přípravku D-PLEX podávaného současně se standardní péčí (SoC), ve srovnání s kontrolním ramenem léčeným SoC, k prevenci pooperační infekce incize po břišní operaci

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

study of D-PLEX in prevention of infections following abdominal surgeries.

Hodnocení D-PLEX v prevenci infekcí po operacích břicha

A.3.2

Name or abbreviated title of the trial where available

Safety and Efficacy of D-PLEX in the Prevention of Post Abdominal Surgery Incisional Infection.

Bezpečnost a účinnost D-PLEX při prevenci infekce incize po břišní chirurgii

A.4.1

Sponsor's protocol code number

D-PLEX311

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04233424

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	PolyPid Ltd.
B.1.3.4	Country	Israel
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	PolyPid Ltd.
B.4.2	Country	Israel
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PolyPid Ltd.
B.5.2	Functional name of contact point	PolyPid Clinical Department
B.5.3	Address:
B.5.3.1	Street Address	Hasivim 18
B.5.3.2	Town/ city	Petach Tikva
B.5.3.3	Post code	4959376
B.5.3.4	Country	Israel
B.5.4	Telephone number	+97274 719 5700
B.5.5	Fax number	+97274 719 5718
B.5.6	E-mail	clinical@polypid.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	D-PLEX
D.3.4	Pharmaceutical form	Powder for implantation paste
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Implantation
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Doxycycline Hyclate
D.3.9.1	CAS number	24390-14-5
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	SUB01830MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/W) percent weight/weight
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.26
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Prevention of post abdominal surgery incisional infection

E.1.1.1

Medical condition in easily understood language

Prevention of infections following abdominal surgeries

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10078408
E.1.2	Term	Surgical site infection
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subjects undergoing an elective colorectal surgery involving resection, with or without a stoma formation, that includes at least 1 abdominal incision that is > 10cm (target incision).
2. Subjects are preoperative hemodynamically stable (BP≤180/110 and >90/60 mmHg, and HR≤100 and >60 bpm, and temperature ≤38.50C and 35.50C).
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.

E.4

Principal exclusion criteria

1. Subjects with suspected/diagnosed intestinal perforation, intra-abdominal abscess,or any emergency/urgent colorectal surgery with acute intestinal obstruction (ex. toxic colitis, ileus/sub-ileus, megacolon, diverticulitis, volvulus, etc.)
2. Subjects who underwent an intra-abdominal surgery within the last 6 months prior to randomization.
3. Subjects with any preoperative active infection or who are receiving any antibiotic therapy in the past 1 week prior to randomization, excluding pre operative prophylaxis.
4. Subjects undergoing concomitant major procedures in addition to the abdominal surgery, including concomitant repair of ventral hernia.
Salpingo-oophorectomy and cholecystectomy are allowed.
5. Subjects who received any anticancer treatment within the last 4 weeks of surgery.
6. Subjects who received radiation for colorectal cancer to the abdomen area, prior to the planned abdominal surgery.
7. Subjects who received oral or IV Doxycycline or Tetracycline family antibiotics 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 reaction
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 who underwent any abdominal surgery and current planned index surgery involves reopening the scar of a prior abdominal surgery performed within the last 3 years.
16. Any subject with an active malignancy, other than resectable non metastatic colorectal cancer, that is the reason for the index surgery, or carcinoma in situ (or other cancer "in situ = Stage 0"), or squamous cell carcinoma of the skin, or basal cell carcinoma of the skin, or a malignancy that has not been in complete clinical remission and without maintenance chemo or immunotherapy for at least 3 years
17. Subjects with other concurrent severe and/or uncontrolled medical condition.
18. Psychiatric or any other disorder that compromises ability to provide informed consent for participation in this study.
19. Chronic alcoholic or drug abuse subjects.
20. Pregnant or breast feeding women or women of child bearing age 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 study.
23. Subjects, who in the opinion of Investigator, are not eligible to participate in the study and/or to comply with the protocol requirements (e.g. due to a cognitive or medical condition).

E.5 End points

E.5.1

Primary end point(s)

Infection rate as measured by the proportion of subjects with an SSI event, occurring within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee.
The blinded and independent adjudication committee review will include all index surgery incisions, regardless of any re-intervention at the target site (i.e. re-opening of the surgery incision, used for the original index surgery), for the determination of infection status. The committee will also assess re-interventions at the primary incision site through the abdominal incision (target)) for the determination of re-intervention due to suspected SSI or due to poor wound healing, including wound dehiscence. Such event as well as all-cause mortality within 30 days post index surgery will be analysed as treatment failure.
Reinterventions for other reasons likely unrelated to the initial treatment (as determined by the blinded independent adjudication committee; e.g. anastomosis leaks, intraabdominal hemorrhage, bowel obstruction), will be not be considered as failures in the primary analysis of the primary endpoint.
Reintervention is defined as re-opening of the surgery incision, used for the original index surgery, in the operation room (OR).
SSI is defined as Deep Incisional Surgical Site Infection (DSSI) and/or Superficial Incisional Surgical Site Infection (SSSI).
Superficial incisional SSI - Infection involves only skin and subcutaneous tissue of the incision and does not include diagnosis/treatment of cellulitis, a stitch abscess alone or a localized stab wound or pin site infection.
Deep incisional SSI - Infection involves deep tissues, such as fascia and muscle layers; this also includes infection involving both superficial and deep incision sites.
An organ/space SSI (e.g.., infection/abscess in the operated organ or peritoneal cavity) will not be accounted as an endpoint event.
Identification of an SSI will be based on CDC/NHSN Patient Safety Component Manual criteria (January 2020, chapter 9).

E.5.1.1

Timepoint(s) of evaluation of this end point

Primary end point will be assessed at day 30

E.5.2

Secondary end point(s)

Key endpoints:
● Infection rate as measured by the proportion of subjects with at least one abdominal target incisional infection event only, occurring within 30 days post abdominal surgery and determined by a blinded and independent adjudication committee.
[abdominal incisional infection is defined as Deep Incisional Surgical Site Infection (DSSI) and/or Superficial Incisional Surgical Site Infection (SSSI)].
● Number (percent) of subjects with at least 1 score of ASEPSIS > 20 within 30 days post abdominal surgery.
Additional endpoints:
● Incidence of SSSI during 30 days post index surgery.
● Incidence of DSSI during 30 days post index surgery.
● All-cause mortality rate within 30 days post randomization.
● All-cause mortality rate within 60 days post randomization.
● Time to adjudicated target incisional SSI post-surgery during 30 days post index surgery.
● Number (percent) of subjects, re-admitted during 30 days post-surgery (for any reason) and experienced adjudicated SSI during this re-admission.
● Number (percent) of subjects who experienced at least 1 surgical re-intervention due to adjudicated SSI during 30 days post-surgery. Re-intervention is defined as re-opening of the surgery incision, used for the original index surgery, in the operation room (OR)

SSI related Additional Endpoints:
● Number (percent) of subjects with adjudicated SSI where at least one Doxycycline-resistant bacteria has grown during the bacteriology tests.
● Number (percent) of Doxycycline-resistant bacteria out of all bacteria that were grown during the bacteriological tests from subjects with adjudicated SSI.
● Number (percent) of subjects who experienced adjudicated SSI during 30 days post-surgery that was treated by IV antibiotic.
● Number of IV antibiotic treatment days administered to subjects experienced adjudicated abdominal incisional SSI during 30 days post-surgery.
● Average of subjects’ cumulative ASEPSIS assessment score (AUC) for subjects with adjudicated SSI during 30 days post-surgery.
● Number (percent) of subjects with at least 1 score of ASEPSIS > 20 in subjects with adjudicated SSI within 30 days post abdominal index surgery.

E.5.2.1

Timepoint(s) of evaluation of this end point

30 days, 60 days

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Israel

United States

Moldova, Republic of

Ukraine

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The last visit of the last subject

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

750

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

200

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

140

F.4.2

For a multinational trial

F.4.2.1

In the EEA

600

F.4.2.2

In the whole clinical trial

950

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-11-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-08-08

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