Clinical Trial Results:
A multicenter, multinational, randomized, controlled, open label study, performed in children with thermal burns, to evaluate the efficacy and safety of NexoBrid as compared to standard of care (SOC) treatment
Summary
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EudraCT number |
2014-003066-24 |
Trial protocol |
CZ ES SK DE BE AT BG NL FR SE GB HU PL IT |
Global end of trial date |
19 Dec 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Sep 2024
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First version publication date |
25 Sep 2024
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MW2012-01-01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02278718 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
US (FDA): IND065448 | ||
Sponsors
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Sponsor organisation name |
MediWound, Ltd.
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Sponsor organisation address |
42 Hayarkon Street, North Industrial Area, Yavne, Israel, 8122745
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Public contact |
Asi Haviv, DMD, Medical Director, MediWound, Ltd., 972 7797141000,
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Scientific contact |
Asi Haviv, DMD, Medical Director, MediWound, Ltd., 972 7797141000,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000142-PIP02-09 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
19 Mar 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
19 Dec 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Dec 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of the trial is:
-To demonstrate enzymatic eschar removal efficacy of NexoBrid by providing earlier, complete eschar removal.
-To demonstrate enzymatic eschar removal efficacy of NexoBrid by reducing patients’ surgical burden and resulting in non inferior final outcomes of cosmesis and function as compared to SOC.
-To assess the safety of NexoBrid compared to SOC.
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Protection of trial subjects |
The study will be carried out in accordance with accepted international standards, which meet regulations relating to Good Clinical Practice (GCP). These standards are drawn from the following guidelines: ICH Guideline for Good Clinical Practice 1.5.96, amended September 1997 (Post step errata July 2002) and Declaration of Helsinki (as amended in Fortaleza, Brazil, October 2013), concerning medical research in humans. In the Netherlands, the NVK (The Netherlands Association for Paediatric Medicine) code of conduct for dealing with subjects’ expressions of objection in the course of the research will be adhered to as well. The investigator(s) will ensure that this study is conducted in full conformity with the principles of the "Declaration of Helsinki" and with the laws and regulations of the participating countries, whichever affords the greater protection to the individual. It is the responsibility of the investigator to obtain informed consent in written form (according to local legal requirements) from each subject participating in this study. All patients will be informed of the aims, methods, anticipated benefits, potential hazards and confidentiality of data. Candidates will also be told that they are free to refuse participation at any time.
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Background therapy |
Patients will be treated in the same way in all study arms (NexoBrid or SOC) except for the Eschar Removal stage which will be performed as per the randomization study arm. Subsequent to complete eschar removal, all wounds will be assessed and treated in the same manner, in accordance with post-eschar removal wound care strategy. Post eschar removal, subjects will undergo Vital Signs and pain assessments, daily, until HD (Hospital Discharge) and weekly assessments of wound progress thereafter, until wound closure. Following wound closure confirmation, subjects will be followed up for 3 months (at week 6 and 12) and after that at 6, 12, 18 and 24 months post wound closure for long term outcomes evaluation. In addition, all subjects will be invited to one additional extended follow up visit that will occur at least 30 months after wound closure confirmation for a blinded assessment of cosmesis, function and QoL evaluation. | ||
Evidence for comparator |
Comparators: Standard of Card (SOC) Conservative, non-surgical treatment by the antimicrobial SSD (Silver Sulphadiazine) dressing followed by daily dressing change and bathing is designed basically to slowly slough and debride the eschar-covered- wound by autolysis without excessive infection. SSD should not be used on a clean bed as it decreases epithelialization. | ||
Actual start date of recruitment |
01 Dec 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 28
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Country: Number of subjects enrolled |
Poland: 2
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Country: Number of subjects enrolled |
Israel: 2
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Country: Number of subjects enrolled |
Georgia: 4
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Country: Number of subjects enrolled |
Ukraine: 12
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Country: Number of subjects enrolled |
India: 30
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Country: Number of subjects enrolled |
Netherlands: 1
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Country: Number of subjects enrolled |
Romania: 8
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Country: Number of subjects enrolled |
Slovakia: 1
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Country: Number of subjects enrolled |
Spain: 3
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Country: Number of subjects enrolled |
United Kingdom: 10
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Country: Number of subjects enrolled |
Belgium: 10
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Country: Number of subjects enrolled |
Bulgaria: 2
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Country: Number of subjects enrolled |
France: 2
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Country: Number of subjects enrolled |
Germany: 14
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Country: Number of subjects enrolled |
Hungary: 15
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Country: Number of subjects enrolled |
Italy: 1
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Worldwide total number of subjects |
145
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EEA total number of subjects |
59
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
45
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Children (2-11 years) |
80
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Adolescents (12-17 years) |
20
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The patients included in this study were hospitalized burn victims with DPT (deep partial thickness) and FT (full thickness) thermal burns | |||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Signing of Informed Consent, demographics, medical history, concomitant medication, physical examination, vital signs, pain assessment, burn etiology, clinical assessment of the burn, randomization | |||||||||||||||||||||||||||
Period 1
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Period 1 title |
12-Week Follow-up
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||||||||
Blinding implementation details |
Assessor was blinded
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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NexoBrid | |||||||||||||||||||||||||||
Arm description |
NexoBrid is presented as partially purified Bromelain powder and gel vehicle for preparation of a gel for cutaneous use. Following mixing of the powder with the gel vehicle, each gram of the prepared product contains 0.09 g partially purified Bromelain. Partially purified Bromelain is a mixture of enzymes extracted from the stem of Ananas comosus (pineapple plant). | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
NexoBrid
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and gel for gel
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Routes of administration |
Cutaneous use
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Dosage and administration details |
Two grams or 5 grams of NexoBrid sterile powder are mixed in 20 grams or 50 grams of sterile Gel Vehicle to obtain NexoBrid Gel. NexoBrid Gel is applied to the burn wound at a dose of 2g NexoBrid/20g Gel per 180cm² for four hours. In most cases, NexoBrid is effective after a single application; however it may be applied for a second time to the same burn area based on the investigator's judgment of debridement efficacy.
NexoBrid should not be applied more than twice to the same burn wound area.
NexoBrid should not be applied to more than 15% TBSA in one session.
Treatment was only applied at the beginning of the Study, no application at the Follow-Up Visits.
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Arm title
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SOC (Standard of Care) | |||||||||||||||||||||||||||
Arm description |
Standard of care. Includes surgical and/or non surgical eschar removal procedures. | |||||||||||||||||||||||||||
Arm type |
Standard of care | |||||||||||||||||||||||||||
Investigational medicinal product name |
Standard of care procedures
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Cream, Cutaneous solution, Ointment
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Routes of administration |
Conjunctival use , Topical use
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Dosage and administration details |
Surgical procedures intended for eschar removal are pre-specified in the protocol for standardization and will include tangential/ minor/ avulsion/ Versajet/ dermabrasion excision.
Non-surgical procedures intended for eschar removal are pre-specified below for standardization and will include the application of antimicrobial solutions (e.g. Dakin’s Solution, Sulfa-Nystatin Solution), ointments/creams (e.g. Bacitracin, Polysporin, Silvadene) and/or Silver dressings (e.g. Mepilex Ag, Aquacel Ag, Acticoat). Non-Surgical procedure is considered as one procedure for the whole period of any continuous dressing changes of more than 24h until either complete eschar removal is achieved or until surgical eschar removal is conducted. The need of either non-surgical or surgical procedures will be determined by the burn specialists and can be repeated as needed until complete debridement.
Treatment was only applied at the beginning of the Study, no application at the Follow-Up Visits.
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Period 2
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Period 2 title |
12-Month Follow-up
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Is this the baseline period? |
No | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||||||||
Blinding implementation details |
Assessor was blinded
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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NexoBrid | |||||||||||||||||||||||||||
Arm description |
NexoBrid is presented as partially purified Bromelain powder and gel vehicle for preparation of a gel for cutaneous use. Following mixing of the powder with the gel vehicle, each gram of the prepared product contains 0.09 g partially purified Bromelain. Partially purified Bromelain is a mixture of enzymes extracted from the stem of Ananas comosus (pineapple plant). | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
NexoBrid
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and gel for gel
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Routes of administration |
Cutaneous use
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Dosage and administration details |
Two grams or 5 grams of NexoBrid sterile powder are mixed in 20 grams or 50 grams of sterile Gel Vehicle to obtain NexoBrid Gel. NexoBrid Gel is applied to the burn wound at a dose of 2g NexoBrid/20g Gel per 180cm² for four hours. In most cases, NexoBrid is effective after a single application; however it may be applied for a second time to the same burn area based on the investigator's judgment of debridement efficacy.
NexoBrid should not be applied more than twice to the same burn wound area.
NexoBrid should not be applied to more than 15% TBSA in one session.
Treatment was only applied at the beginning of the Study, no application at the Follow-Up Visits.
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Arm title
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SOC (Standard of Care) | |||||||||||||||||||||||||||
Arm description |
Standard of care. Includes surgical and/or non surgical eschar removal procedures. | |||||||||||||||||||||||||||
Arm type |
Standard of care | |||||||||||||||||||||||||||
Investigational medicinal product name |
Standard of care procedures
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Cream, Cutaneous solution, Ointment
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Routes of administration |
Conjunctival use , Topical use
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Dosage and administration details |
Surgical procedures intended for eschar removal are pre-specified in the protocol for standardization and will include tangential/ minor/ avulsion/ Versajet/ dermabrasion excision.
Non-surgical procedures intended for eschar removal are pre-specified below for standardization and will include the application of antimicrobial solutions (e.g. Dakin’s Solution, Sulfa-Nystatin Solution), ointments/creams (e.g. Bacitracin, Polysporin, Silvadene) and/or Silver dressings (e.g. Mepilex Ag, Aquacel Ag, Acticoat). Non-Surgical procedure is considered as one procedure for the whole period of any continuous dressing changes of more than 24h until either complete eschar removal is achieved or until surgical eschar removal is conducted. The need of either non-surgical or surgical procedures will be determined by the burn specialists and can be repeated as needed until complete debridement.
Treatment was only applied at the beginning of the Study, no application at the Follow-Up Visits.
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Period 3
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Period 3 title |
24-Month Follow-up
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Is this the baseline period? |
No | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||||||||
Blinding implementation details |
Assessor was blinded
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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NexoBrid | |||||||||||||||||||||||||||
Arm description |
NexoBrid is presented as partially purified Bromelain powder and gel vehicle for preparation of a gel for cutaneous use. Following mixing of the powder with the gel vehicle, each gram of the prepared product contains 0.09 g partially purified Bromelain. Partially purified Bromelain is a mixture of enzymes extracted from the stem of Ananas comosus (pineapple plant). | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
NexoBrid
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and gel for gel
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Routes of administration |
Cutaneous use
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Dosage and administration details |
Two grams or 5 grams of NexoBrid sterile powder are mixed in 20 grams or 50 grams of sterile Gel Vehicle to obtain NexoBrid Gel. NexoBrid Gel is applied to the burn wound at a dose of 2g NexoBrid/20g Gel per 180cm² for four hours. In most cases, NexoBrid is effective after a single application; however it may be applied for a second time to the same burn area based on the investigator's judgment of debridement efficacy.
NexoBrid should not be applied more than twice to the same burn wound area.
NexoBrid should not be applied to more than 15% TBSA in one session.
Treatment was only applied at the beginning of the Study, no application at the Follow-Up Visits.
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Arm title
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SOC (Standard of Care) | |||||||||||||||||||||||||||
Arm description |
Standard of care. Includes surgical and/or non surgical eschar removal procedures. | |||||||||||||||||||||||||||
Arm type |
Standard of care | |||||||||||||||||||||||||||
Investigational medicinal product name |
Standard of care procedures
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Cream, Cutaneous solution, Ointment
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Routes of administration |
Conjunctival use , Topical use
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Dosage and administration details |
Surgical procedures intended for eschar removal are pre-specified in the protocol for standardization and will include tangential/ minor/ avulsion/ Versajet/ dermabrasion excision.
Non-surgical procedures intended for eschar removal are pre-specified below for standardization and will include the application of antimicrobial solutions (e.g. Dakin’s Solution, Sulfa-Nystatin Solution), ointments/creams (e.g. Bacitracin, Polysporin, Silvadene) and/or Silver dressings (e.g. Mepilex Ag, Aquacel Ag, Acticoat). Non-Surgical procedure is considered as one procedure for the whole period of any continuous dressing changes of more than 24h until either complete eschar removal is achieved or until surgical eschar removal is conducted. The need of either non-surgical or surgical procedures will be determined by the burn specialists and can be repeated as needed until complete debridement.
Treatment was only applied at the beginning of the Study, no application at the Follow-Up Visits.
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Period 4
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Period 4 title |
30-Month Follow-up
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Is this the baseline period? |
No | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||||||||
Blinding implementation details |
Assessor was blinded
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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NexoBrid | |||||||||||||||||||||||||||
Arm description |
NexoBrid is presented as partially purified Bromelain powder and gel vehicle for preparation of a gel for cutaneous use. Following mixing of the powder with the gel vehicle, each gram of the prepared product contains 0.09 g partially purified Bromelain. Partially purified Bromelain is a mixture of enzymes extracted from the stem of Ananas comosus (pineapple plant). | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
NexoBrid
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and gel for gel
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Routes of administration |
Cutaneous use
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Dosage and administration details |
Two grams or 5 grams of NexoBrid sterile powder are mixed in 20 grams or 50 grams of sterile Gel Vehicle to obtain NexoBrid Gel. NexoBrid Gel is applied to the burn wound at a dose of 2g NexoBrid/20g Gel per 180cm² for four hours. In most cases, NexoBrid is effective after a single application; however it may be applied for a second time to the same burn area based on the investigator's judgment of debridement efficacy.
NexoBrid should not be applied more than twice to the same burn wound area.
NexoBrid should not be applied to more than 15% TBSA in one session.
Treatment was only applied at the beginning of the Study, no application at the Follow-Up Visits.
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Arm title
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SOC (Standard of Care) | |||||||||||||||||||||||||||
Arm description |
Standard of care. Includes surgical and/or non surgical eschar removal procedures. | |||||||||||||||||||||||||||
Arm type |
Standard of care | |||||||||||||||||||||||||||
Investigational medicinal product name |
Standard of care procedures
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Investigational medicinal product code |
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Other name |
||||||||||||||||||||||||||||
Pharmaceutical forms |
Cream, Cutaneous solution, Ointment
|
|||||||||||||||||||||||||||
Routes of administration |
Conjunctival use , Topical use
|
|||||||||||||||||||||||||||
Dosage and administration details |
Surgical procedures intended for eschar removal are pre-specified in the protocol for standardization and will include tangential/ minor/ avulsion/ Versajet/ dermabrasion excision.
Non-surgical procedures intended for eschar removal are pre-specified below for standardization and will include the application of antimicrobial solutions (e.g. Dakin’s Solution, Sulfa-Nystatin Solution), ointments/creams (e.g. Bacitracin, Polysporin, Silvadene) and/or Silver dressings (e.g. Mepilex Ag, Aquacel Ag, Acticoat). Non-Surgical procedure is considered as one procedure for the whole period of any continuous dressing changes of more than 24h until either complete eschar removal is achieved or until surgical eschar removal is conducted. The need of either non-surgical or surgical procedures will be determined by the burn specialists and can be repeated as needed until complete debridement.
Treatment was only applied at the beginning of the Study, no application at the Follow-Up Visits.
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Baseline characteristics reporting groups
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Reporting group title |
12-Week Follow-up
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
NexoBrid
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Reporting group description |
NexoBrid is presented as partially purified Bromelain powder and gel vehicle for preparation of a gel for cutaneous use. Following mixing of the powder with the gel vehicle, each gram of the prepared product contains 0.09 g partially purified Bromelain. Partially purified Bromelain is a mixture of enzymes extracted from the stem of Ananas comosus (pineapple plant). | ||
Reporting group title |
SOC (Standard of Care)
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Reporting group description |
Standard of care. Includes surgical and/or non surgical eschar removal procedures. | ||
Reporting group title |
NexoBrid
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Reporting group description |
NexoBrid is presented as partially purified Bromelain powder and gel vehicle for preparation of a gel for cutaneous use. Following mixing of the powder with the gel vehicle, each gram of the prepared product contains 0.09 g partially purified Bromelain. Partially purified Bromelain is a mixture of enzymes extracted from the stem of Ananas comosus (pineapple plant). | ||
Reporting group title |
SOC (Standard of Care)
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Reporting group description |
Standard of care. Includes surgical and/or non surgical eschar removal procedures. | ||
Reporting group title |
NexoBrid
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Reporting group description |
NexoBrid is presented as partially purified Bromelain powder and gel vehicle for preparation of a gel for cutaneous use. Following mixing of the powder with the gel vehicle, each gram of the prepared product contains 0.09 g partially purified Bromelain. Partially purified Bromelain is a mixture of enzymes extracted from the stem of Ananas comosus (pineapple plant). | ||
Reporting group title |
SOC (Standard of Care)
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Reporting group description |
Standard of care. Includes surgical and/or non surgical eschar removal procedures. | ||
Reporting group title |
NexoBrid
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Reporting group description |
NexoBrid is presented as partially purified Bromelain powder and gel vehicle for preparation of a gel for cutaneous use. Following mixing of the powder with the gel vehicle, each gram of the prepared product contains 0.09 g partially purified Bromelain. Partially purified Bromelain is a mixture of enzymes extracted from the stem of Ananas comosus (pineapple plant). | ||
Reporting group title |
SOC (Standard of Care)
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Reporting group description |
Standard of care. Includes surgical and/or non surgical eschar removal procedures. | ||
Subject analysis set title |
Full Analysis Set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Includes all patients who were randomized into the trial.
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End point title |
Time to complete eschar removal | |||||||||
End point description |
Eschar removal was measured at the end of debridement starting from randomisation date. Eschar removal (days) can demonstrate superiority of NexoBrid over SoC as measured by a survival analysis of incidence of complete eschar removal when complete eschar removal was achieved for each patient, from the time of randomization.
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
From the time of randomization - baseline until 12-Month Follow-Up.
|
|||||||||
|
||||||||||
Statistical analysis title |
Efficacy | |||||||||
Statistical analysis description |
Time until complete eschar removal was defined as the time until complete echar removal has been achieved.
|
|||||||||
Comparison groups |
NexoBrid v SOC (Standard of Care)
|
|||||||||
Number of subjects included in analysis |
145
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
= 0.0008 | |||||||||
Method |
Wilcoxon-Gehan | |||||||||
Confidence interval |
|
||||||||||
End point title |
Percent Wound Area Surgically Excised for Eschar Removal | |||||||||
End point description |
Demonstrate superiority over SOC in reduction in surgical need for excisional eschar removal as measured by an analysis of percent wound area surgically excised for eschar removal (tangential/ minor/ avulsion/ Versajet and/or dermabrasion excision).
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
From the time of randomization - baseline until 12-Month Follow-up.
|
|||||||||
|
||||||||||
Statistical analysis title |
% wound area surgically excised for eschar removal | |||||||||
Comparison groups |
NexoBrid v SOC (Standard of Care)
|
|||||||||
Number of subjects included in analysis |
145
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
< 0.0001 | |||||||||
Method |
ANOVA | |||||||||
Parameter type |
Mean difference (net) | |||||||||
Point estimate |
45.5
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
31.6 | |||||||||
upper limit |
58.9 | |||||||||
Variability estimate |
Standard error of the mean
|
|||||||||
Dispersion value |
6.83
|
|
||||||||||||||||
End point title |
Cosmesis and Function | |||||||||||||||
End point description |
To demonstrate non-inferiority to SoC in quality of scars of burns (using MVSS) treated with NexoBrid, measured at 12 and 24 month from wound closure
|
|||||||||||||||
End point type |
Primary
|
|||||||||||||||
End point timeframe |
Cosmesis assessment at 12-Month and 24-Month Follow-Up.
|
|||||||||||||||
|
||||||||||||||||
Statistical analysis title |
MVSS Regression Results 12-Month Follow-Up | |||||||||||||||
Comparison groups |
NexoBrid v SOC (Standard of Care)
|
|||||||||||||||
Number of subjects included in analysis |
145
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority | |||||||||||||||
P-value |
< 0.0001 | |||||||||||||||
Method |
Regression, Linear | |||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||
Point estimate |
2.76
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
1.85 | |||||||||||||||
upper limit |
3.67 | |||||||||||||||
Variability estimate |
Standard deviation
|
|||||||||||||||
Dispersion value |
0.91
|
|||||||||||||||
Statistical analysis title |
MVSS Regression Results 24- Month Follow-Up | |||||||||||||||
Comparison groups |
NexoBrid v SOC (Standard of Care)
|
|||||||||||||||
Number of subjects included in analysis |
132
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority | |||||||||||||||
P-value |
< 0.0001 | |||||||||||||||
Method |
Regression, Linear | |||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||
Point estimate |
2.39
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
1.52 | |||||||||||||||
upper limit |
3.25 | |||||||||||||||
Variability estimate |
Standard deviation
|
|||||||||||||||
Dispersion value |
0.86
|
|
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Adverse events information
|
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Timeframe for reporting adverse events |
Per protocol amendment, the extended long-term FU visit at ≥ 30M did not include
documentation of AEs and SAEs that occurred after the 24M FU visit.
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Adverse event reporting additional description |
For 24M FU Period, TEAEs (Treatment-Emergent Adverse Events) were analysed separately for 2 different periods:
1. Between the 12 months FU and the 24 months FU (12M-24M FU Period)
2. In the cumulative period (0-24M FU Period).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24
|
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Reporting groups
|
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Reporting group title |
NexoBrid AE
|
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Reporting group description |
Summary of Treatment-Emergent Adverse Events by System Organ Class, Preferred Term, and Maximum Intensity – 12M-24M FU Period (SAS) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SOC AE
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||
Substantial protocol amendments (globally) |
|||||||
Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
||||||
27 May 2014 |
Protocol Version 4 |
||||||
08 Sep 2014 |
Protocol Version 5 |
||||||
02 Dec 2014 |
Protocol Version 6 |
||||||
28 Dec 2014 |
Protocol Version 6.01 |
||||||
31 Dec 2014 |
Protocol Version 6.02 |
||||||
02 Jan 2017 |
Protocol Version 7 |
||||||
28 Mar 2017 |
Protocol Version 7.01 |
||||||
01 Jun 2017 |
Protocol Version 7.02 |
||||||
26 Dec 2017 |
Protocol Version 8 |
||||||
29 Jul 2019 |
Protocol Version 9.01 |
||||||
26 Aug 2019 |
Protocol Version 9 |
||||||
16 Nov 2020 |
Protocol Version 10 |
||||||
16 Nov 2020 |
Protocol Version 10.01 |
||||||
16 Jun 2021 |
Protocol Version 11 |
||||||
16 Jun 2021 |
Protocol Version 11.01 |
||||||
Interruptions (globally) |
|||||||
Were there any global interruptions to the trial? Yes | |||||||
|
|||||||
Limitations and caveats |
|||||||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
None reported |