CHF6467 SAD and MAD in Patients With Diabetic Foot Ulcer

NCT04077671 | Completed Phase 1

• 2 other identifiers: CLI-06467AA1-012018-001724-19
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the safety and tolerability of single and multiple days' topical dosing with CHF6467 in subjects with diabetic foot ulcer (DFU).

Conditions

Diabetic Neuropathic Foot Ulcers

Keywords

DFU; Diabetic Foot Ulcers; Diabetic Neuropathic Foot Ulcers

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  SAD: Serial of timepoints until 72 hours post dose

• Pharmacodynamic: Ulcer area after multiple administration

  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

  MAD: Serial of timepoints at Day 1, Day 2, Day 4, Day 7, Day 10, Day 13, Day 14, Day 21 and Day 28

Study Arms (6)

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.

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.

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.

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.

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.

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.

Biological: CHF6467 active

Interventions

CHF6467 active BIOLOGICAL

CHF6467, is mutated form of the human Nerve Growth Factor (NGF).

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

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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%.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead
• Comac Medical: collaborator

Study Sites (1)

Comac Medical Ltd.

Sofia, 1618, Bulgaria

Location

Related Links

• Study Record on EU Clinical Trials Register including results
• Lay Summaries of study results available in the CHIESI Clinical Study Register

MeSH Terms

Conditions

Diabetic Foot

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Foot Ulcer; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

Study Officials

• Iliya Lozev, MD

  Comac Medical

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: SAD - Single Ascending Dose \& MAD - Multiple Ascending Dose

Study Record Dates

• First Submitted: March 28, 2019
• First Posted: September 4, 2019
• Study Start: October 17, 2018
• Primary Completion: January 7, 2021
• Study Completion: January 7, 2021
• Last Updated: February 23, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1)