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CACIPLIQ20 in Wound Healing in Subjects With Epidermolysis Bullosa (MATHBULL)

Primary Purpose

Epidermolysis Bullosa Dystrophica, Epidermolysis Bullosa, Junctional

Status
Not yet recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
CACIPLIQ20
Placebo
Sponsored by
Organ, Tissue, Regeneration, Repair and Replacement
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Epidermolysis Bullosa Dystrophica

Eligibility Criteria

3 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Diagnosis of Dystrophic or Junctional EB. 3 years ≤ age ≤ 18 years At least one active wound at inclusion Informed consent form signed by the patient's legal representative; if the patient is minor but capable of providing consent, additional signed consent from the patient. Patient and caregiver must be willing to comply with all protocol requirements. Exclusion Criteria: Use of any investigational drug within the last 30 days before enrolment. Current or former malignancy. Pregnancy or breastfeeding during the study. Females of childbearing potential who are not abstinent and not practicing a medically acceptable method of contraception. Use of CACIPLIQ20 within the last 30 days before enrolment. Patients intolerant to one of the study device components or to heparinoids.

Sites / Locations

  • Hopital Necker - enfants malades

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

A: CACIPLIQ20 before placebo

B: placebo before CACIPLIQ20

Arm Description

Arm A will receive at first CACIPLIQ20 (experimental product) for 1 month, followed by 1-month washout, then 1 month of saline (placebo comparator).

Arm B will receive at first saline (placebo comparator) for 1 month, followed by 1-month washout, then 1 month of CACIPLIQ20 (experimental product).

Outcomes

Primary Outcome Measures

Change in total lesioned skin surface
Change in total lesioned skin surface from baseline* to the end of the CACIPLIQ20 vs Placebo treatment periods * Baseline 1 at inclusion/before treatment period 1, and Baseline 2 at the end of washout/before treatment period 2 Change in total lesioned skin surface at the end of each treatment period will be assessed blindly regarding treatment allocation, using the SilhouetteConnect™ software in reference to "Baseline 1" and "Baseline 2".

Secondary Outcome Measures

The rate of device related serious adverse events
The rate of device related adverse events
The rate of procedure related adverse events
The rate of procedure related serious adverse events
The rate of all adverse events (AEs).
The rate of all serious adverse events (SAE)
Proportion of wounds achieving complete closure at the end of the CACIPLIQ20 versus Placebo treatment periods
This parameter will be assessed with the ARANZ Silhouette® system by comparing wounds areas before and after each treatment period.
Mean CGI at the end of the CACIPLIQ20 versus Placebo treatment periods
The CGI (clinical assessment) will be rated on the following sevenpoint scale: = Very much improved-nearly all better; good level of functioning; minimal symptoms; represents a very substantial change = Much improved-notably better with significant reduction of symptoms; increase in the level of functioning but some symptoms remain = Minimally improved-slightly better with little or no clinically meaningful reduction of symptoms. Represents very little change in basic clinical status, level of care, or functional capacity = No change-symptoms remain essentially unchanged = Minimally worse-slightly worse but may not be clinically meaningful; may represent very little change in basic clinical status or functional capacity = Much worse-clinically significant increase in symptoms and diminished functioning = Very much worse-severe exacerbation of symptoms and loss of functioning
Mean SGI at the end of the CACIPLIQ20 versus Placebo treatment periods
The SGI (subject/family assessment) will be rated on the following sevenpoint scale: = Very much improved-nearly all better; good level of functioning; minimal symptoms; represents a very substantial change = Much improved-notably better with significant reduction of symptoms; increase in the level of functioning but some symptoms remain = Minimally improved-slightly better with little or no clinically meaningful reduction of symptoms. Represents very little change in basic clinical status, level of care, or functional capacity = No change-symptoms remain essentially unchanged = Minimally worse-slightly worse but may not be clinically meaningful; may represent very little change in basic clinical status or functional capacity = Much worse-clinically significant increase in symptoms and diminished functioning = Very much worse-severe exacerbation of symptoms and loss of functioning
Change in pain assessed from baseline to the end of the CACIPLIQ20 versus Placebo treatment periods (for patients from 3 to 4 years of age)
Change in pain will be assessed at the end of the one-month treatment period 1 and 2 compared to baseline 1 and baseline 2, respectively, using the "FLACC scale" for patients from 3 to 4 years of age. FLACC: Face Legs Activity Cry Consolability. Score range for the FLACC scale is between 0-10 where higher score represents more pain.
Change in pain assessed from baseline to the end of the CACIPLIQ20 versus Placebo treatment periods (for patients 4 years of age and older)
Change in pain will be assessed at the end of the one-month treatment period 1 and 2 compared to baseline 1 and baseline 2, respectively, using the "Wong Faces Pain Scale" for patients 4 years of age and older. The Wong Faces Pain Scale rates pain on a 0-10 scale, where higher score represents more pain.
Change in itching assessed from baseline to the end of the CACIPLIQ20 versus Placebo treatment periods
Change in itching will be assessed at the end of one-month treatment period 1 and 2 with eference to baseline 1 and baseline 2, respectively. Itching will be measured using the "Itch Man Pruritus Assessment Tool". In patients from 3 to 6 years of age, assessments will be performed by caretakers whereas patients who are 6 years of age and older will self-report their itching using the "Itch Man Pruritus Assessment Tool". Itching assessments based on the following scores: 0=Comfortable, no itch; 1=itches a little, does not interfere with activity; 2=itches more, sometimes interferes with activity; 3=itches a lot, difficult to be still, concentrate; 4=itches most terribly, impossible to sit still or concentrate.

Full Information

First Posted
August 7, 2023
Last Updated
August 17, 2023
Sponsor
Organ, Tissue, Regeneration, Repair and Replacement
Collaborators
Euraxi Pharma, ARANZ Medical
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1. Study Identification

Unique Protocol Identification Number
NCT06007235
Brief Title
CACIPLIQ20 in Wound Healing in Subjects With Epidermolysis Bullosa
Acronym
MATHBULL
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Crossover, Pilot Stage Clinical Trial Evaluating CACIPLIQ20 in Wound Healing in Subjects With Epidermolysis Bullosa
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Organ, Tissue, Regeneration, Repair and Replacement
Collaborators
Euraxi Pharma, ARANZ Medical

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Epidermolysis bullosa (EB) is a group of inherited disorders characterized by fragility of the skin and mucous membranes within the basement membrane zone. It is characterized by moderate to excessive fragility of epithelial tissues with prototypic blistering or erosions following minimal trauma (mechanobullous dermatoses). The chronic pain associated with EB, the hardship placed on caregivers, and the high risk for complications places a considerable psychosocial burden on both patients and their families. Despite considerable research to advance the understanding of EB pathophysiology, no treatments have been approved by regulatory authorities to date. Heparan sulfates are key elements of the Extra Cellular Matrix scaffold which act both as linkers, bridging structural matrix proteins such as collagens, laminin and as storage and protector sites to communication peptides, playing a pivotal role in the regulation of cell proliferation, migration and differentiation that are all required for tissue regeneration and repair. CACIPLIQ20 is a bioengineered structural analogue of heparan sulfate glycosaminoglycans. Numerous experimental studies have provided strong evidence that CACIPLIQ20 promotes tissue regeneration by reconstructing the cellular microenvironment following tissue injury. CACIPLIQ20 is currently a class III CE marked medical device (NSAI-0050 CE MARK ECDECNL-A4 (6) and EC Annex II of the directive. NL-A4 (7)) with the following indications: Chronic ulcers showing no tendency to heal after 6 months of standard care, or still unhealed after 12 months: Pressure ulcers. Peripheral arterial disease (such as Stage IV Leriche & Fontaine) ulcers. Diabetic ulcers (including amputation). Preliminary results from several published and unpublished case reports (Al Malak and Barritault, 2012; Bodemer, unpublished observations) suggest that CACIPLIQ20 is safe and can improve wound healing and reduce pain in patients with epidermolysis bullosa. The goal of the MATHBULL study is to confirm preliminary observations in a placebo-controlled double-blind pilot study. The results of this pilot study will help to design a pivotal study.
Detailed Description
The patients are outpatients at inclusion and may be already followed by the investigators, and they have not yet been treated with CACIPLIQ20 for at least one month. These patients will be randomly allocated (1:1 ratio) to Arm A and B. Every patient will have two treatment periods. Arm A will receive at first CACIPLIQ20 for 1 month, followed by 1-month washout then 1-month Placebo, and the reverse sequence (Placebo followed by CACIPLIQ20) in Arm B. The sponsor, investigator and patient will remain blinded to the treatment Arm in which a patient will be randomized until the end of the study and database lock. Two baselines will be defined before the two treatment periods, Baseline 1 at inclusion/before treatment period 1, and Baseline 2 at the end of washout/before treatment period 2. For each patient, all active wounds will be treated by CACIPLIQ20 or Placebo, which will be added to the best standard of care decided by the participating physicians. Treatments will be provided in indistinguishable spray bottles, labelled with treatment numbers using a randomization list provided by an independent statistician. CACIPLIQ20 or Placebo will be applied every 3 to 4 days for 30 days. Patients will be followed every month according to investigators' standard practices. At least five visits will be programmed during the study, including Inclusion Visit, End of Treatment Period 1 Visit at Month 1, End of Washout Visit at Month 2, End of Treatment Period 2 Visit at Month 3, End of Study Visit at Month 4. In addition to these visits, two phone calls will be organized 15 days after the start of each treatment period to identify potential adverse events. At each visit, the investigator will take pictures of treated wounds with an imaging device (Silhouette®), in order to assess the total lesioned skin surface.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epidermolysis Bullosa Dystrophica, Epidermolysis Bullosa, Junctional

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Blinding codes on treatments
Allocation
Randomized
Enrollment
16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A: CACIPLIQ20 before placebo
Arm Type
Other
Arm Description
Arm A will receive at first CACIPLIQ20 (experimental product) for 1 month, followed by 1-month washout, then 1 month of saline (placebo comparator).
Arm Title
B: placebo before CACIPLIQ20
Arm Type
Other
Arm Description
Arm B will receive at first saline (placebo comparator) for 1 month, followed by 1-month washout, then 1 month of CACIPLIQ20 (experimental product).
Intervention Type
Device
Intervention Name(s)
CACIPLIQ20
Intervention Description
CACIPLIQ20 contains RGTA heparan sulphate mimetics
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Saline solution in identical spray bottles
Primary Outcome Measure Information:
Title
Change in total lesioned skin surface
Description
Change in total lesioned skin surface from baseline* to the end of the CACIPLIQ20 vs Placebo treatment periods * Baseline 1 at inclusion/before treatment period 1, and Baseline 2 at the end of washout/before treatment period 2 Change in total lesioned skin surface at the end of each treatment period will be assessed blindly regarding treatment allocation, using the SilhouetteConnect™ software in reference to "Baseline 1" and "Baseline 2".
Time Frame
After 1 month of treatment
Secondary Outcome Measure Information:
Title
The rate of device related serious adverse events
Time Frame
Up to 4 months
Title
The rate of device related adverse events
Time Frame
Up to 4 months
Title
The rate of procedure related adverse events
Time Frame
Up to 4 months
Title
The rate of procedure related serious adverse events
Time Frame
Up to 4 months
Title
The rate of all adverse events (AEs).
Time Frame
Up to 4 months
Title
The rate of all serious adverse events (SAE)
Time Frame
Up to 4 months
Title
Proportion of wounds achieving complete closure at the end of the CACIPLIQ20 versus Placebo treatment periods
Description
This parameter will be assessed with the ARANZ Silhouette® system by comparing wounds areas before and after each treatment period.
Time Frame
After 1 month of treatment
Title
Mean CGI at the end of the CACIPLIQ20 versus Placebo treatment periods
Description
The CGI (clinical assessment) will be rated on the following sevenpoint scale: = Very much improved-nearly all better; good level of functioning; minimal symptoms; represents a very substantial change = Much improved-notably better with significant reduction of symptoms; increase in the level of functioning but some symptoms remain = Minimally improved-slightly better with little or no clinically meaningful reduction of symptoms. Represents very little change in basic clinical status, level of care, or functional capacity = No change-symptoms remain essentially unchanged = Minimally worse-slightly worse but may not be clinically meaningful; may represent very little change in basic clinical status or functional capacity = Much worse-clinically significant increase in symptoms and diminished functioning = Very much worse-severe exacerbation of symptoms and loss of functioning
Time Frame
After 1 month of treatment
Title
Mean SGI at the end of the CACIPLIQ20 versus Placebo treatment periods
Description
The SGI (subject/family assessment) will be rated on the following sevenpoint scale: = Very much improved-nearly all better; good level of functioning; minimal symptoms; represents a very substantial change = Much improved-notably better with significant reduction of symptoms; increase in the level of functioning but some symptoms remain = Minimally improved-slightly better with little or no clinically meaningful reduction of symptoms. Represents very little change in basic clinical status, level of care, or functional capacity = No change-symptoms remain essentially unchanged = Minimally worse-slightly worse but may not be clinically meaningful; may represent very little change in basic clinical status or functional capacity = Much worse-clinically significant increase in symptoms and diminished functioning = Very much worse-severe exacerbation of symptoms and loss of functioning
Time Frame
After 1 month of treatment
Title
Change in pain assessed from baseline to the end of the CACIPLIQ20 versus Placebo treatment periods (for patients from 3 to 4 years of age)
Description
Change in pain will be assessed at the end of the one-month treatment period 1 and 2 compared to baseline 1 and baseline 2, respectively, using the "FLACC scale" for patients from 3 to 4 years of age. FLACC: Face Legs Activity Cry Consolability. Score range for the FLACC scale is between 0-10 where higher score represents more pain.
Time Frame
After 1 month of treatment
Title
Change in pain assessed from baseline to the end of the CACIPLIQ20 versus Placebo treatment periods (for patients 4 years of age and older)
Description
Change in pain will be assessed at the end of the one-month treatment period 1 and 2 compared to baseline 1 and baseline 2, respectively, using the "Wong Faces Pain Scale" for patients 4 years of age and older. The Wong Faces Pain Scale rates pain on a 0-10 scale, where higher score represents more pain.
Time Frame
After 1 month of treatment
Title
Change in itching assessed from baseline to the end of the CACIPLIQ20 versus Placebo treatment periods
Description
Change in itching will be assessed at the end of one-month treatment period 1 and 2 with eference to baseline 1 and baseline 2, respectively. Itching will be measured using the "Itch Man Pruritus Assessment Tool". In patients from 3 to 6 years of age, assessments will be performed by caretakers whereas patients who are 6 years of age and older will self-report their itching using the "Itch Man Pruritus Assessment Tool". Itching assessments based on the following scores: 0=Comfortable, no itch; 1=itches a little, does not interfere with activity; 2=itches more, sometimes interferes with activity; 3=itches a lot, difficult to be still, concentrate; 4=itches most terribly, impossible to sit still or concentrate.
Time Frame
After 1 month of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of Dystrophic or Junctional EB. 3 years ≤ age ≤ 18 years At least one active wound at inclusion Informed consent form signed by the patient's legal representative; if the patient is minor but capable of providing consent, additional signed consent from the patient. Patient and caregiver must be willing to comply with all protocol requirements. Exclusion Criteria: Use of any investigational drug within the last 30 days before enrolment. Current or former malignancy. Pregnancy or breastfeeding during the study. Females of childbearing potential who are not abstinent and not practicing a medically acceptable method of contraception. Use of CACIPLIQ20 within the last 30 days before enrolment. Patients intolerant to one of the study device components or to heparinoids.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Frederic Sedel, MD, PhD
Phone
+33 (0)1 83627895
Email
frederic.sedel@otr3.com
First Name & Middle Initial & Last Name or Official Title & Degree
Martin Inizan
Email
martin.inizan@otr3.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christine Bodemer, MD, PhD
Organizational Affiliation
Hopital Necker - enfants malades
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Necker - enfants malades
City
Paris
ZIP/Postal Code
75000
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christine Bodemer, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

CACIPLIQ20 in Wound Healing in Subjects With Epidermolysis Bullosa

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