Epidermolysis Bullosa DystrophicaMATHBULLNCT06007235
CACIPLIQ20 in Wound Healing in Subjects With Epidermolysis Bullosa
A study testing CACIPLIQ20 in people with Epidermolysis Bullosa Dystrophica and Epidermolysis Bullosa, Junctional, run by Organ, Tissue, Regeneration, Repair and Replacement at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 3 to 18 years
- Conditions the study is for
- Epidermolysis Bullosa Dystrophica, Epidermolysis Bullosa, Junctional
- What is being tested?
- CACIPLIQ20
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteFrance
- Study dates
- 29 Jan 2024to Sep 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Martin Inizan contact
France1 site, 1 recruiting
- Recruiting
Hopital Necker - enfants malades
Paris, 75000
Christine Bodemer, MD, PhD
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Crossover, Pilot Stage Clinical Trial Evaluating CACIPLIQ20 in Wound Healing in Subjects With Epidermolysis Bullosa
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:
Read more
- 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.
Read the 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.
- Being tested
- CACIPLIQ20, Placebo
- Medical subject headings
- Epidermolysis Bullosa Dystrophica, Epidermolysis Bullosa, Junctional
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CACIPLIQ20Device
CACIPLIQ20 contains RGTA heparan sulphate mimetics
PlaceboDrug
Saline solution in identical spray bottles
| Study group | Role | What they receive |
|---|---|---|
| A: CACIPLIQ20 before placebo | Other | Arm A will receive at first CACIPLIQ20 (experimental product) for 1 month, followed by 1-month washout, then 1 month of saline (placebo comparator). Receives: Device: CACIPLIQ20; Drug: Placebo |
| B: placebo before CACIPLIQ20 | Other | Arm B will receive at first saline (placebo comparator) for 1 month, followed by 1-month washout, then 1 month of CACIPLIQ20 (experimental product). Receives: Device: CACIPLIQ20; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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".
Measured: After 1 month of treatment
Secondary outcomes (12)
The rate of device related serious adverse events
Measured: Up to 4 months
The rate of device related adverse events
Measured: Up to 4 months
The rate of procedure related adverse events
Measured: Up to 4 months
The rate of procedure related serious adverse events
Measured: Up to 4 months
The rate of all adverse events (AEs).
Measured: Up to 4 months
The rate of all serious adverse events (SAE)
Measured: Up to 4 months
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.
Measured: After 1 month of treatment
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
Measured: After 1 month of treatment
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
Measured: After 1 month of treatment
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.
Measured: After 1 month of treatment
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.
Measured: After 1 month of treatment
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.
Measured: After 1 month of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2023
- Study start29 Jan 2024
- Primary completionSep 2024 (estimated)
- Study completionSep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epidermolysis Bullosa DystrophicaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Organ, Tissue, Regeneration, Repair and Replacement
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Euraxi Pharma, ARANZ Medical
- Responsible party
- Sponsor
- Investigators
- Christine Bodemer, MD, PhD, Principal investigator, Hopital Necker - enfants malades
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06007235
- Sponsor's protocol ID
- 2022-A01774-39
- Acronym
- MATHBULL
- Status last verified
- Feb 2024
- First submitted
- 7 Aug 2023
- Last updated
- 13 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Crossover, Pilot Stage Clinical Trial Evaluating CACIPLIQ20 in Wound Healing in Subjects With Epidermolysis Bullosa
- ClinicalTrials.gov ID
- NCT06007235
- Acronym / sponsor ID
- MATHBULL / 2022-A01774-39
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Organ, Tissue, Regeneration, Repair and ReplacementIndustry (pharma, biotech, devices)
- Collaborators
- Euraxi Pharma, ARANZ Medical
- Study start
- 29 Jan 2024 (actual)
- Primary completion
- Sep 2024 (estimated)
- Study completion
- Sep 2024 (estimated)
- First posted
- 23 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A: CACIPLIQ20 before placebo | Other | Device: CACIPLIQ20, Drug: PlaceboArm A will receive at first CACIPLIQ20 (experimental product) for 1 month, followed by 1-month washout, then 1 month of saline (placebo comparator). |
| B: placebo before CACIPLIQ20 | Other | Device: CACIPLIQ20, Drug: PlaceboArm B will receive at first saline (placebo comparator) for 1 month, followed by 1-month washout, then 1 month of CACIPLIQ20 (experimental product). |
Who may qualify
- Ages
- 3 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CACIPLIQ20CACIPLIQ20 contains RGTA heparan sulphate mimetics | Device | A: CACIPLIQ20 before placebo, B: placebo before CACIPLIQ20 |
| PlaceboSaline solution in identical spray bottles | Drug | A: CACIPLIQ20 before placebo, B: placebo before CACIPLIQ20 |
Primary outcome
Change in total lesioned skin surface
Time frame: After 1 month of treatment
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".
12 secondary outcomes
The rate of device related serious adverse events
Time frame: Up to 4 months
The rate of device related adverse events
Time frame: Up to 4 months
The rate of procedure related adverse events
Time frame: Up to 4 months
The rate of procedure related serious adverse events
Time frame: Up to 4 months
The rate of all adverse events (AEs).
Time frame: Up to 4 months
The rate of all serious adverse events (SAE)
Time frame: Up to 4 months
Proportion of wounds achieving complete closure at the end of the CACIPLIQ20 versus Placebo treatment periods
Time frame: After 1 month of treatment
Mean CGI at the end of the CACIPLIQ20 versus Placebo treatment periods
Time frame: After 1 month of treatment
Mean SGI at the end of the CACIPLIQ20 versus Placebo treatment periods
Time frame: After 1 month of treatment
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)
Time frame: After 1 month of treatment
Change in pain assessed from baseline to the end of the CACIPLIQ20 versus Placebo treatment periods (for patients 4 years of age and older)
Time frame: After 1 month of treatment
Change in itching assessed from baseline to the end of the CACIPLIQ20 versus Placebo treatment periods
Time frame: After 1 month of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Inizan contact
Christine Bodemer, MD, PhD principal investigator
Hopital Necker - enfants malades
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CACIPLIQ20 in people with Epidermolysis Bullosa Dystrophica and Epidermolysis Bullosa, Junctional, run by Organ, Tissue, Regeneration, Repair and Replacement at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Frederic Sedel, MD, PhD (+33 (0)1 83627895, frederic.sedel@otr3.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in total lesioned skin surface (time frame: After 1 month of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2024.