Clinical trial NCT03888053: BB-101 for Treatment of Diabetic Lower Leg and Foot Ulcers
Official title: A Phase 1, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of Topical BB-101 (rhNEGF) for the Treatment of Diabetic Lower Leg and Foot Ulcers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetic Foot Ulcer
Lead sponsor: Blue Blood Biotech Corp.
Sponsor class: INDUSTRY
First posted: 2019-03-25
Enrollment: 14
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, placebo-controlled, sequential dose escalation study in diabetic subjects with a diabetic lower leg or foot ulcer. All subjects will receive standard-of-care ulcer treatment from screening through the last study visit.

Detailed description: This is a randomized, double-blind, placebo-controlled, sequential dose escalation study in diabetic subjects with a diabetic lower leg or foot ulcer. All subjects will receive standard-of-care ulcer treatment from screening through the last study visit.

The study will be conducted at multiple investigational sites located in Taiwan. Additional sites and countries may be added during the course of the study if required.

Eligibility criteria: Inclusion Criteria:

* Male or female, 20 years of age and older.
* Type 1 or type 2 diabetes mellitus.
* Glycosylated hemoglobin (HbA1c) of ≤12%.
* A target ulcer on the lower leg or foot that meets the following criteria at screening:

  1. located below knees,
  2. Area of 0.5 - 10.0 cm\^2 following sharp debridement , as measured at Visit 1 and confirmed at Visit 2,
  3. Extending through the epidermis and dermis but not involving bone, tendon or ligament,
  4. Present for ≥4 weeks prior to Visit 1 despite appropriate care, and
  5. Ulcer without clinical signs and symptoms of infection.
* Adequate arterial blood supply to the lower leg or foot under study, to be measured either by doppler ultrasonography, ankle brachial pressure index (ABPI) ≥0.70, or toe pressure \>30 mmHg.
* Female subjects of childbearing potential must have a negative serum pregnancy test prior to first dose of study medication and must agree to use an effective method of contraception throughout the study. Females who are surgically sterile or have been postmenopausal for at least 1 year (12 consecutive months without menses) are exempted from these criteria. Effective methods of contraception include oral contraceptives, injectable or implantable hormonal methods, intrauterine devices, tubal ligation (if performed more than 1 year prior to screening), or double barrier contraception (e.g., diaphragm+condom).
* Subject agrees to comply with ulcer care regimen for the duration of the study.
* Subject is able to understand and sign an informed consent form and willing to comply with all study procedures.

Exclusion Criteria:

* Clinical signs and symptoms of infection of target ulcer assessed by clinical evaluation (the presence of infection is defined by ≥2 classic findings of inflammation or purulence).
* Presence of cellulitis or gangrene on the lower leg or foot under study.
* Presence of another open ulcer \<2 cm away from target ulcer, on the same lower leg or foot.
* Target ulcer on the heel.
* Target ulcer caused primarily by untreated arterial insufficiency or with an etiology not related to diabetes.
* Subjects with ulcers related to an incompletely healed amputation wound.
* Acute or chronic osteomyelitis affecting the area of the target ulcer.
* Any structural deformity of the lower leg or foot under study that would prevent off- loading of the target ulcer, including acute Charcot osteoarthropathy.
* Previous use of a platelet-derived product (e.g., becaplermin) or other growth factors on the target ulcer within 4 weeks prior to Visit 1.
* Previous use of autologous graft or allogeneic graft, or dermal substitute or living skin equivalent (e.g., Dermagraft® or Apligraf®) on the target ulcer or hyperbaric oxygen therapy within 2 weeks prior to Visit 1.
* Use of any topical antimicrobials or enzymatic debridement treatment, to treat the target ulcer within 7 days prior to Visit 1.
* Treatment with systemic corticosteroids other than for inhalation, immunosuppressive agents, radiation therapy, or chemotherapeutic agent within 30 days prior to Visit 1 or likelihood to receive any of these therapies during study participation.
* History of cancer or current cancer, with the exception of adequately treated or excised non-melanoma skin cancer.
* Vasculitis, connective tissue diseases, or any medical conditions known to impair ulcer healing, other than diabetes.
* Sickle cell disease.
* Clinically significant electrocardiogram (ECG) abnormality, as determined by the Investigator.
* Any of the following laboratory results at screening: serum creatinine \>2.5 mg/dL; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2x upper limit of normal (ULN).
* Poor nutritional status (serum albumin \< 2.5 g/dL).
* A history of drug or alcohol abuse that could compromise compliance or safety.
* History of human immunodeficiency virus (HIV) infection.
* Known sensitivity to any component of BB-101 or placebo.
* Participation in a clinical trial of an investigational drug or device within 30 days of study entry.
* Pregnancy, lactation, or plans to become pregnant within 6 months.
* Any social or medical condition that, in the opinion of the Investigator, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
* History of non-compliance with treatment or clinical visit attendance.

Primary outcomes:
measure: Incidence and severity of local reactions
timeFrame: 6 weeks
measure: Incidence and severity of adverse events
timeFrame: 6 weeks
measure: Incidence of clinical laboratory abnormalities
timeFrame: 6 weeks
measure: Change from baseline in ECG
timeFrame: 6 weeks
measure: Change from baseline in blood pressure
timeFrame: 6 weeks
measure: Change from baseline in heart rate
timeFrame: 6 weeks
measure: Change from baseline in body temperature
timeFrame: 6 weeks
measure: Presence of anti-BB-101 antibodies
timeFrame: 6 weeks
Secondary outcomes:
measure: Proportion of subjects with target ulcer that heals within the 4-week treatment period
timeFrame: 4 weeks
measure: To evaluate plasma concentration of BB-101
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
Study officials:
affiliation: National Cheng-Kung University Hospital
name: Shih-Chen Pan, MD
role: PRINCIPAL_INVESTIGATOR
References: