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.

Study Overview

• Status: Completed
• Conditions: Diabetic Foot Ulcer
• Intervention / Treatment: Biological: BB-101

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan
    • National Cheng Kung University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: BB-101 Treatment Arm; BB-101 liquid formulation concentration of 2 µg/mL or 20 µg/mL will be applied on the target lower leg or foot ulcer once a day for 4 consecutive weeks.	Biological: BB-101; Within each cohort, 8 subjects will be randomized to receive BB-101 and 4 subjects to receive placebo.
Placebo Comparator: Placebo Arm; Placebo will be applied on the target lower leg or foot ulcer once a day for 4 consecutive weeks.	Biological: BB-101; Within each cohort, 8 subjects will be randomized to receive BB-101 and 4 subjects to receive placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of local reactions	To assess the incidence of local reactions for target ulcer and surrounding area and record the severity	6 weeks
Incidence and severity of adverse events	To assess the incidence of adverse events and record the severity	6 weeks
Incidence of clinical laboratory abnormalities	To assess the incidence of clinical laboratory abnormalities	6 weeks
Change from baseline in ECG	To assess the change of baseline in ECG	6 weeks
Change from baseline in blood pressure	To assess the change of baseline in in blood pressure	6 weeks
Change from baseline in heart rate	To assess the change of baseline in heart rate	6 weeks
Change from baseline in body temperature	To assess the change of baseline in body temperature	6 weeks
Presence of anti-BB-101 antibodies	To assess the immunogenecity for BB-101	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with target ulcer that heals within the 4-week treatment period	complete healing defined as re-epithelialization without drainage and dressing requirement	4 weeks
To evaluate plasma concentration of BB-101	To evaluate plasma concentration of BB-101	4 weeks

Collaborators and Investigators

• Sponsor: Blue Blood Biotech Corp.
• Investigators: Principal Investigator: Shih-Chen Pan, MD, National Cheng-Kung University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2018
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: February 20, 2019
• First Submitted That Met QC Criteria: March 21, 2019
• First Posted (Actual): March 25, 2019

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer; Ulcer
• Other Study ID Numbers: BB-101-001A

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No