BB-101 for Treatment of Diabetic Lower Leg and Foot Ulcers

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

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.

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.

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 - 20.0 cm^2 following sharp debridement , as measured at Visit 1 and confirmed at Visit 2,
  3. Extending through the epidermis and dermis and may have reached bone, tendon or joint capsule (Grade 1 to grade 2 according to Wagner Classification System for diabetic foot ulcer),
  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) ≥0.50, or toe pressure >30 mmHg.

Note: For subjects with 0.7>ABPI ≧0.5, adequate treatments must be provided to the subject for improving circulation by medication or surgical procedures, etc. ABPI is the ratio of the highest systolic blood pressure of the dorsalis pedis or posterior tibial arteries of each leg to the highest of the left and right arm brachial systolic blood pressure.

• 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 basal cell carcinoma, squamous cell carcinoma in situ of the skin, or cervical carcinoma in situ that has been treated with no evidence of recurrence, or squamous cell carcinoma of the skin that has been treated with no evidence of recurrence within 5 years prior to administration of any study agent).

• 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, including but not limited to:

  1. QTc ≥450 ms in male subject or ≥460 ms in female subject at screening
  2. Significant ST-segment-T wave (ST-T) changes or left bundle branch block (LBBB)

• Any unstable cardiovascular disease, as determined by the Investigator, that renders the subject inappropriate for participating the study, including but not limited to:

  1. Has a history of, or concurrent congestive heart failure (CHF) defined by New York Heart Association (NYHA) Classes III or IV.
  2. Myocardial infarction (MI), unstable angina, percutaneous coronary intervention, or coronary artery bypass graft surgery within 12 weeks prior to Screening. Subjects with adequately treated stable angina, per physician investigator's assessment, may be included.

• 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 drug administration.

• 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.