Diabetic Neuropathic Foot Ulcers (DFU) Texas Scale Grade 1A and 2A MedDRA version: 21.1 Level: LLT Classification code 10012664 Term: Diabetic foot ulcer System Organ Class: 100000004858
Conditions
Interventions
Product Code: CHF6467
Pharmaceutical Form: Cutaneous solution
INN or Proposed INN: Recombinant human mutant nerve growth factor painless ( hNGFp)
Current Sponsor code: CHF6467
Other descriptive name:
Sponsors
Chiesi Farmaceutici S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part 1 SD and Part 2 MD: Subjects must meet all the following criteria in order to be eligible for enrolment into the study: 1. Subject’s written informed consent obtained prior to any study-related procedure; 2. Male or female subject aged 18 – 80 years (extremes inclusive), diagnosed with Type I or Type II diabetes mellitus, with glycosylated haemoglobin (HbA1c) = 10%. 3. 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). 4. 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: a) Placement of an intrauterine device (IUD) or intrauterine system (IUS). b) Hormonal contraception (implantable, patch, oral). c) Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical vaults/caps) with spermicidal foam/gel/film/cream/suppository. d) Male Partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). 5. 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. 6. Presence of at least one diabetic foot ulcer meeting the following criteria: a) 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) b) SD: Present for 6 weeks to 12 months, and of 3 – 5 cm 2 in area following sharp debridement, confirmed at screening. MD: 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 mmHg b) Toe pressure (plethysmography) >50 mmHg c) Doppler ultrasound (biphasic or triphasic waveforms) on at least two vessels at the ankle consistent with adequate blood flow to the affected extremity, as determined by SoC. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 y
Exclusion criteria
Exclusion criteria: Part 1 SD and Part 2 MD: Subjects must meet none of the following criteria in order to be eligible for enrolment into the study: 1. 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. 2. Subject with: a) 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). b) Gangrene or necrosis on any part of the affected limb. c) Active or chronic Charcot's foot on the study limb. d) Planned vascular surgery, angioplasty or thrombolysis or previous revascularization procedure performed within 1 month prior to enrolment. e) 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). f) Ulcer(s) of non-diabetic aetiology. g) Previous Lisfranc or Chopart's amputations on the same target foot. h) Actual or recent (3 weeks) antibiotic therapy for any reason. i) Bedridden subjects or subjects with a life expectancy less than one year. 3. Use of any growth factor therapy in the 3 months prior to screening. 4. 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. 5. 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 and CRO Medical Monitor should be consulted). 6. Subject undergoing haemodialysis or peritoneal dialysis or with chronic renal insufficiency (plasma creatinine > 2 mg/dl). 7. Subject with significantly abnormal key laboratory parameters interfering with the safety of the subject according to the PI judgement.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the safety and tolerability of single and multiple days’ topical dosing with CHF6467 in subjects with DFU.;Secondary Objective: • To assess the pharmacokinetic profile of systemically available drug following single and multiple days’ topical dosing with CHF6467 in subjects with DFU; • To assess the pharmacodynamic effects of multiple days’ topical dosing with CHF6467 on the healing of DFU over a 12-week period. • To assess the potential for immunogenicity through the evaluation of the presence of CHF6467 Antidrug Antibodies (ADA).;Primary end point(s): Part 1 SD: Safety: ?ssessed throughout the trial (Screening, Treatment Period and Follow-up): • Adverse Events (AEs) and Adverse Drug Reactions (ADRs) • Vital signs: Systolic (SBP) and Diastolic (DBP) Blood Pressure • Triplicate 12-lead ECG • 12-lead ECG parameters extracted from Holter (HR, PR, QRS, QTcF, QT) • Clinical laboratory evaluations (chemistry, haematology and urinalysis). Part 2 MD: Safety: ?ssessed throughout the trial (Screening, Treatment Period and Follow-up): • AEs and ADRs; • Vital signs: SBP, DBP; temperature; • Triplicate 12-lead ECG; (Should any ECG/cardiovascular findings emerge from Part 1 of the study, the SAC may also implement Holter monitoring for part, or all, of Part 2, as indicated); • 12-lead ECG parameters extracted from Holter (HR, PR, QRS, QTcF, QT); • 24h Holter ECG abnormal findings (total pauses >2.5 secs, atrial fibrillation and atrial flutter, ventricular runs, premature atrial contractions (PAC) burden, premature ventricular contractions (PVC) burden, aberrant morphologies); 0-24h heart rate (from 24h Holter ECG) and hourly average HR; • Clinical laboratory evaluations (chemistry, haematology and urinalysis).;Timepoint(s) of evaluation of this end point: Indicated above. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 SD: Pharmacokinetic variables: The following PK parameters will be derived from CHF6467 serum concentrations: On Day 1, 2, 3 and 4: • AUC0-12h, AUC00-24h, AUC0-t, AUC0-8, Cmax, tmax, t½, CL/F, Vd/F; • AUC0-12h DN, AUC00-24h DN, AUC0-t DN, AUC0-8 DN, Cmax DN. Immunogenicity variables: • Antidrug antibody (ADA) serum concentrations will be evaluated on Day 1 and during the first visit of Week 4 (Day 24) • ADA presence/absence and titer Part 2 MD: Pharmacokinetic variables: The following PK parameters will be derived from CHF6467 serum concentrations: • On Day 1: AUC0-12h, Cmax, and tmax,; • From Day 2 to Day 13: Ctrough • On the last day of drug administration (Day 14): AUC0-12h, AUC0-t, AUC0-8, Ctrough, Cmax, Cmin, tmax, tmin, Cav, and Rac, t½, CL/F, and Vd/F. Immunogenicity variables: • Antidrug antibody (ADA) serum concentrations will be evaluated on Day 1 prior to the first dose application, on Day 15 prior to discharge, on Day 24 (Week 4), Day 52 (Week 8) and on Day 80 (Week 12). • ADA presence/absence and titer Pharmacodynamic/ Efficacy variables: • Mean reduction in target ulcer area and volume from Baseline to D14, D21, D28, D56 and D84; • Time to healing of the target ulcer area and volume. Healing will be defined as “complete recovery”. Different “healing” definitions will also be applied (Partial reduction: 50%, 66%, 75%).;Timepoint(s) of evaluation of this end point: Indicated above. | — |
Countries
Bulgaria
Contacts
Public ContactClinical Project Manager
Chiesi Farmaceutici S.p.A.
Outcome results
None listed