Diabetic Neuropathic Foot UlcersPhase 1/2NCT04077671
CHF6467 SAD and MAD in Patients With Diabetic Foot Ulcer
A Phase 1/2 study testing CHF6467 active in people with Diabetic Neuropathic Foot Ulcers, run by Chiesi Farmaceutici S.p.A. at 1 site in Bulgaria.
Trial summary
To assess the safety and tolerability of single and multiple days' topical dosing with CHF6467 in subjects with diabetic foot ulcer (DFU). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Diabetic Neuropathic Foot Ulcers
- What is being tested?
- CHF6467 active
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 93 participants
- Where
- 1 siteBulgaria
- Study dates
- 17 Oct 2018to 7 Jan 2021
- Phase
- Phase 1/2
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject's written informed consent obtained prior to any study-related procedure;
- Male or female subject, aged 18 - 80 years (extremes inclusive), diagnosed with Type I or Type II diabetes mellitus, with glycosylated haemoglobin (HbA1c) ≤ 10%.
- Female subjects of non-childbearing potential (WONCBP):
- they must report surgical sterilization (performed at least 6 months prior to screening), or
- menopause (must have had no regular menstrual bleeding for at least one year prior to screening, age ≥ 45 years and FSH at screening ≥ 40 mIU/ml).
- Female subject with childbearing potential (WOCBP): they must be using one or more of the following reliable methods of contraception during the study period and at least within 90 days after the last study drug administration:
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- Placement of an intrauterine device (IUD) or intrauterine system (IUS).
- Hormonal contraception (implantable, patch, oral).
- Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical vaults/caps) with spermicidal foam/gel/film/cream/suppository.
- Male Partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate).
- Male subjects; they must be using two effective methods of contraception during the entire study period and not donate sperm within 90 days after the last study drug administration.
- Presence of at least one diabetic foot ulcer meeting the following criteria:
- Diagnosed as a full-thickness, neuropathic DFU, located at or distal to the malleolus (excluding ulcers between the toes but including those of the heel)
- SAD: Present for 6 weeks to 12 months, and of 3 - 5 cm2 in area following sharp debridement, confirmed at screening.
- MAD: Present for 6 weeks to 12 months, and of 3 - 6 cm2 in area following sharp debridement confirmed at screening, and of 2-5 cm2 after the 2 weeks run-in period with an area reduction compared to screening <50%.
- A minimum 1 cm margin between the qualifying study ulcer and any other ulcers on the specified foot.
- SAD: Ulcer must have a depth ≥ 5 mm at some point in its area and be graded 1A according to "The University of Texas Staging System for Diabetic Foot Ulcers" (22), with no capsule, tendon or bone exposed and no tunnelling, undermining, or sinus tracts, after the initial sharp debridement, confirmed at screening.
- MAD: Ulcer must have a depth ≥ 5 mm at some point in its area and be graded 1A or 2A according to "The University of Texas Staging System for Diabetic Foot Ulcers" (22), after the initial sharp debridement, confirmed at screening.
- Subject must be able to hold the target ulcer in such a position and orientation that the study medication can be applied without significant loss of substance through run-off, until the dressing has been applied.
- Adequate vascular perfusion of the affected limb demonstrated within 30 days prior to screening, as defined by at least one of the following:
- Ankle-Brachial Index (ABI) ≥ 0.9 and ≤ 1.2, confirmed by transcutaneous oxygen partial pressure (TcPO2) >50 mmHg
- Toe pressure (plethysmography) >50 mmHg
- Doppler ultrasound (biphasic or triphasic waveforms) at least on two vessels at the ankle consistent with adequate blood flow to the affected extremity, as determined by SoC.
Who cannot join
- For females only: pregnant or lactating female subject, confirmed by a positive serum pregnancy test at screening and a urine test performed on Day -1.
- Subject with:
- Ulcer(s) accompanied by infected cellulitis, osteomyelitis, or clinical signs or symptoms of infection confirmed by a cultural exam made on the material taken off from the ulcer according to the technique described in the guidelines for diagnosis and management of diabetic foot infections of the Infectious Diseases Society of the Americas (IDSA) (19).
- Gangrene or necrosis on any part of the affected limb.
- Active or chronic Charcot's foot on the study limb.
- Planned vascular surgery, angioplasty or thrombolysis or previous revascularization procedure performed within 1 month prior to enrolment.
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- SD only: Ulcers involving exposure of tendon, bone, or joint capsule (It is acceptable to have ulcers extending through the dermis and into subcutaneous tissue with presence of granulation tissue).
- Ulcer(s) of non-diabetic aetiology.
- Previous Lisfranc or Chopart's amputations on the same target foot.
- Actual or recent (3 weeks) antibiotic therapy for any reason.
- Bedridden subjects or subjects with a life expectancy less than one year.
- Use of any growth factor therapy in the 3 months prior to screening.
- History of malignancy in the 5 years prior to screening or those with a strong family history of cancer (e.g. familial cancer disorders), with the exception of squamous cell or basal cell carcinoma of the skin that has been definitively treated.
- Clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurological, psychiatric, immunological, gastrointestinal, haematological or metabolic disease that is, in the opinion of the Investigator, not stabilised or may otherwise impact subject safety or study results (in cases of doubt, the Sponsor's Clinical Research Physician should be consulted).
- Subject undergoing haemodialysis or peritoneal dialysis or with chronic renal insufficiency (plasma creatinine > 2 mg/dl).
- Subject with significantly abnormal key laboratory parameters interfering with the safety of the patient according to the PI judgement.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profiles of CHF6467 After Single and Repeated Ascending Doses in Subjects With Diabetic Neurophatic Foot Ulcers (DFU).
To assess the safety and tolerability of single and multiple days' topical dosing with CHF6467 in subjects with diabetic foot ulcer (DFU).
Read the detailed description
This first in human study is designed to investigate the tolerability, safety, pharmacokinetics and preliminarily pharmacodynamics following topical administration of single and multiple ascending doses of CHF6467 in subjects diagnosed with diabetic foot ulcer (DFU).
- Conditions
- Diabetic Neuropathic Foot Ulcers
- Being tested
- CHF6467 active
- Keywords
- DFU, Diabetic Foot Ulcers, Diabetic Neuropathic Foot Ulcers
- Medical subject headings
- Diabetic Foot
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CHF6467 activeBiological
CHF6467, is mutated form of the human Nerve Growth Factor (NGF).
| Study group | Role | What they receive |
|---|---|---|
| SAD - Cohort A - CHF6467 0.3 µg/mm2 | Experimental | Cohort A: will be administered with CHF6467 0.3 µg/mm2 ulcer area as single dose. Receives: Biological: CHF6467 active |
| SAD - Cohort B - CHF6467 1 µg/mm2 | Experimental | Cohort B: will be administered with 1 µg/mm2 ulcer area as single dose. Receives: Biological: CHF6467 active |
| SAD - Cohort C - CHF6467 3 µg/mm2 | Experimental | Cohort C: will be administered with 3 µg/mm2 ulcer area as single dose. Receives: Biological: CHF6467 active |
| SAD - Cohort D - CHF6467 6 µg/mm2 | Experimental | Cohort D: will be administered with 6 µg/mm2 ulcer area as single dose. Receives: Biological: CHF6467 active |
| MAD - Cohort E - CHF6467 0.3 or 1 µg/mm2 | Experimental | Cohort E: will be administered with 0.3 or 1 µg/mm2 ulcer area (total daily dose) as multiple dose (14 days). The dose will be selected based on the SAD results. Receives: Biological: CHF6467 active |
| MAD - Cohort F - CHF6467 1 or 3 µg/mm2 | Experimental | Cohort F: will be administered with 1 or 3 µg/mm2 ulcer area (total daily dose) as multiple dose (14 days). The dose will be selected based on the SAD results. Receives: Biological: CHF6467 active |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Emergent Adverse Events (TEAEs)
During the SAD and the MAD, the number of events and the number and percentage of subjects experiencing TEAEs, treatment emergent ADRs, serious TEAEs, non-serious TEAEs, severe TEAEs, TEAEs leading to discontinuation of study drug and TEAEs leading to death will be presented by treatment.
Measured: SAD: From Day 1 up to Day 28; MAD: From Day 1 up to Day 84;
Secondary outcomes (3)
Pharmacokinetics: AUC0-72h after single administration
During the SAD: Dose proportionality of CHF6467 for AUC0-72h, and classical PK parameters will be calculated
Measured: SAD: Serial of timepoints until 72 hours post dose
Pharmacodynamic: Ulcer area after multiple administration
MAD: Ulcer area measurements expressend in cm2 over time after multiple administration
Measured: MAD: From Day 1 to Days 4, 7, 10, 14, 17, 21, 24, 28, 31, 35, 38, 42, 45, 49, 52, 56, 59, 63, 66, 70, 73, 77, 80 and 84
Pharmacokinetics: AUC0 to infinit after multiple administration
During the MAD: Dose proportionality of CHF6467 for AUC 0 to infinit, and classical PK parameters will be calculated
Measured: MAD: Serial of timepoints at Day 1, Day 2, Day 4, Day 7, Day 10, Day 13, Day 14, Day 21 and Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2019
- Study start17 Oct 2018
- Primary completion7 Jan 2021
- Study completion7 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic Neuropathic Foot UlcersStudies of the same condition, open and under way.
- More trials run by Chiesi Farmaceutici S.p.A.The sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- SAD - Single Ascending Dose \& MAD - Multiple Ascending Dose
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chiesi Farmaceutici S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Comac Medical
- Responsible party
- Sponsor
- Investigators
- Iliya Lozev, MD, Principal investigator, Comac Medical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04077671
- Sponsor's protocol ID
- CLI-06467AA1-01
- Other IDs
- 2018-001724-19, 2018
- Status last verified
- Feb 2022
- First submitted
- 28 Mar 2019
- Last updated
- 23 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profiles of CHF6467 After Single and Repeated Ascending Doses in Subjects With Diabetic Neurophatic Foot Ulcers (DFU).
- ClinicalTrials.gov ID
- NCT04077671
- Acronym / sponsor ID
- CLI-06467AA1-01
- Conditions
- Diabetic Neuropathic Foot Ulcers
- Keywords
- DFU, Diabetic Foot Ulcers, Diabetic Neuropathic Foot Ulcers
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Chiesi Farmaceutici S.p.A.Industry (pharma, biotech, devices)
- Collaborators
- Comac Medical
- Study start
- 17 Oct 2018 (actual)
- Primary completion
- 7 Jan 2021 (actual)
- Study completion
- 7 Jan 2021 (actual)
- First posted
- 4 Sep 2019 (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.
To assess the safety and tolerability of single and multiple days' topical dosing with CHF6467 in subjects with diabetic foot ulcer (DFU).
Detailed description
This first in human study is designed to investigate the tolerability, safety, pharmacokinetics and preliminarily pharmacodynamics following topical administration of single and multiple ascending doses of CHF6467 in subjects diagnosed with diabetic foot ulcer (DFU).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 6
- Model description
- SAD - Single Ascending Dose \& MAD - Multiple Ascending Dose
| Arm | Type | Receives |
|---|---|---|
| SAD - Cohort A - CHF6467 0.3 µg/mm2 | Experimental | Biological: CHF6467 activeCohort A: will be administered with CHF6467 0.3 µg/mm2 ulcer area as single dose. |
| SAD - Cohort B - CHF6467 1 µg/mm2 | Experimental | Biological: CHF6467 activeCohort B: will be administered with 1 µg/mm2 ulcer area as single dose. |
| SAD - Cohort C - CHF6467 3 µg/mm2 | Experimental | Biological: CHF6467 activeCohort C: will be administered with 3 µg/mm2 ulcer area as single dose. |
| SAD - Cohort D - CHF6467 6 µg/mm2 | Experimental | Biological: CHF6467 activeCohort D: will be administered with 6 µg/mm2 ulcer area as single dose. |
| MAD - Cohort E - CHF6467 0.3 or 1 µg/mm2 | Experimental | Biological: CHF6467 activeCohort E: will be administered with 0.3 or 1 µg/mm2 ulcer area (total daily dose) as multiple dose (14 days). The dose will be selected based on the SAD results. |
| MAD - Cohort F - CHF6467 1 or 3 µg/mm2 | Experimental | Biological: CHF6467 activeCohort F: will be administered with 1 or 3 µg/mm2 ulcer area (total daily dose) as multiple dose (14 days). The dose will be selected based on the SAD results. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Subject's written informed consent obtained prior to any study-related procedure;
- Male or female subject, aged 18 - 80 years (extremes inclusive), diagnosed with Type I or Type II diabetes mellitus, with glycosylated haemoglobin (HbA1c) ≤ 10%.
- Female subjects of non-childbearing potential (WONCBP):
- Female subject with childbearing potential (WOCBP): they must be using one or more of the following reliable methods of contraception during the study period and at least within 90 days after the last study drug administration:
- Male subjects; they must be using two effective methods of contraception during the entire study period and not donate sperm within 90 days after the last study drug administration.
Key exclusion criteria (16 listed)
- For females only: pregnant or lactating female subject, confirmed by a positive serum pregnancy test at screening and a urine test performed on Day -1.
- Subject with:
- Use of any growth factor therapy in the 3 months prior to screening.
- History of malignancy in the 5 years prior to screening or those with a strong family history of cancer (e.g. familial cancer disorders), with the exception of squamous cell or basal cell carcinoma of the skin that has been definitively treated.
- Clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurological, psychiatric, immunological, gastrointestinal, haematological or metabolic disease that is, in the opinion of the Investigator, not stabilised or may otherwise impact subject safety or study results (in cases of doubt, the Sponsor's Clinical Research Physician should be consulted).
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 |
|---|---|---|
| CHF6467 activeCHF6467, is mutated form of the human Nerve Growth Factor (NGF). | Biological | MAD - Cohort E - CHF6467 0.3 or 1 µg/mm2, MAD - Cohort F - CHF6467 1 or 3 µg/mm2, SAD - Cohort A - CHF6467 0.3 µg/mm2, SAD - Cohort B - CHF6467 1 µg/mm2, SAD - Cohort C - CHF6467 3 µg/mm2, SAD - Cohort D - CHF6467 6 µg/mm2 |
Primary outcome
Treatment Emergent Adverse Events (TEAEs)
Time frame: SAD: From Day 1 up to Day 28; MAD: From Day 1 up to Day 84;
During the SAD and the MAD, the number of events and the number and percentage of subjects experiencing TEAEs, treatment emergent ADRs, serious TEAEs, non-serious TEAEs, severe TEAEs, TEAEs leading to discontinuation of study drug and TEAEs leading to death will be presented by treatment.
3 secondary outcomes
Pharmacokinetics: AUC0-72h after single administration
Time frame: SAD: Serial of timepoints until 72 hours post dose
Pharmacodynamic: Ulcer area after multiple administration
Time frame: MAD: From Day 1 to Days 4, 7, 10, 14, 17, 21, 24, 28, 31, 35, 38, 42, 45, 49, 52, 56, 59, 63, 66, 70, 73, 77, 80 and 84
Pharmacokinetics: AUC0 to infinit after multiple administration
Time frame: MAD: Serial of timepoints at Day 1, Day 2, Day 4, Day 7, Day 10, Day 13, Day 14, Day 21 and Day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2022.
- Study Record on EU Clinical Trials Register including resultsLink provided by the sponsor.
- Lay Summaries of study results available in the CHIESI Clinical Study RegisterLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Iliya Lozev, MD principal investigator
Comac Medical
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CHF6467 active in people with Diabetic Neuropathic Foot Ulcers, run by Chiesi Farmaceutici S.p.A. at 1 site in Bulgaria.
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 23 inclusion and 16 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: finished, as of the sponsor's last update on 23 Feb 2022. 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 Bulgaria. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment Emergent Adverse Events (TEAEs) (time frame: SAD: From Day 1 up to Day 28; MAD: From Day 1 up to Day 84;). 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 23 Feb 2022.