Clinical Trials List
Protocol NumberBB-101-001A
NCT Number(ClinicalTrials.gov Identfier)NCT03888053
2016-04-01 - 2021-12-01
Phase I
Not yet recruiting2
Recruiting3
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
-
Trial Applicant
PROTECH PHARMASERVICES CORPORATION
-
Sponsor
Blue Blood Biotech Corp.
-
Trial scale
Taiwan Multiple Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 林進達 Division of Plastic Surgery
- Shun-Cheng Chang Division of Plastic Surgery
- 曾元生 Division of Plastic Surgery
- 喬浩禹 Division of Plastic Surgery
- 施宥任 Division of Plastic Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 陳國熏 Division of Plastic Surgery
- 吳益嘉 Division of Plastic Surgery
- HSIAO-CHEN LEE Division of Plastic Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
National Taiwan University Hospital
Taiwan National PI
潘信誠
Co-Principal Investigator
- Tak-Wah Wong Division of Dermatology
- 謝式洲 Division of Plastic Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Treatment of Diabetic Lower Leg and Foot Ulcers
Objectives
Primary:
To assess the safety, tolerability, and immunogenicity of the 4-week treatment with BB-101 as compared to placebo.
Secondary:
To evaluate the efficacies of treatment with BB-101 verus placebo on ulcer healing.
To evaluate plasma concentration of BB-101.
Test Drug
BB-101
Active Ingredient
rhNEGF
Dosage Form
Vial
Dosage
20
Endpoints
Primary Safety Endpoints:
Incidence and severity of local reactions (target ulcer and surrounding area assessed for presence and severity of erythema, edema, and pain).
Incidence and severity of adverse events(AEs).
Incidence of clinical laboratory abnormalities (hematology, chemistry, coagulation, and urinalysis).
Change from baseline in ECG.
Change from baseline in vital sign measurements(blood pressure, heart rate, and body temperature).
Presence of anti-BB-101 antibodies at Days 1 (predose), 14,28, and 42 (14-day follow-up).
Secondary Endpoints:
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).
Changes in ulcer surface area at Days 3, 7, 14, 21, and 28 or early discontinuation, compared to baseline.
Plasma concentration of BB-101.
Incidence and severity of local reactions (target ulcer and surrounding area assessed for presence and severity of erythema, edema, and pain).
Incidence and severity of adverse events(AEs).
Incidence of clinical laboratory abnormalities (hematology, chemistry, coagulation, and urinalysis).
Change from baseline in ECG.
Change from baseline in vital sign measurements(blood pressure, heart rate, and body temperature).
Presence of anti-BB-101 antibodies at Days 1 (predose), 14,28, and 42 (14-day follow-up).
Secondary Endpoints:
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).
Changes in ulcer surface area at Days 3, 7, 14, 21, and 28 or early discontinuation, compared to baseline.
Plasma concentration of BB-101.
Inclution Criteria
Inclusion Criteria:
1. Male or female, 20 years of age and older.
2. Type 1 or type 2 diabetes mellitus.
3. Glycosylated hemoglobin (HbA1c) of ≤12%.
4. A target ulcer on the lower leg or foot that meets the following criteria at screening:
a. located below knees,
b. Area of 0.5 – 20.0 cm2
following sharp debridement , as measured at Visit 1 and confirmed at Visit 2,
c. 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),
d. Present for 4 weeks prior to Visit 1 despite appropriate care, and
e. Ulcer without clinical signs and symptoms of infection.
5. 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.
6. 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).
7. Subject agrees to comply with ulcer care regimen for the duration of the study.
8. Subject is able to understand and sign an informed consent form and willing to comply with all study procedures.
1. Male or female, 20 years of age and older.
2. Type 1 or type 2 diabetes mellitus.
3. Glycosylated hemoglobin (HbA1c) of ≤12%.
4. A target ulcer on the lower leg or foot that meets the following criteria at screening:
a. located below knees,
b. Area of 0.5 – 20.0 cm2
following sharp debridement , as measured at Visit 1 and confirmed at Visit 2,
c. 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),
d. Present for 4 weeks prior to Visit 1 despite appropriate care, and
e. Ulcer without clinical signs and symptoms of infection.
5. 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.
6. 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).
7. Subject agrees to comply with ulcer care regimen for the duration of the study.
8. Subject is able to understand and sign an informed consent form and willing to comply with all study procedures.
Exclusion Criteria
Exclusion Criteria:1. 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).
2. Presence of cellulitis or gangrene on the lower leg or foot under study.
3. Presence of another open ulcer <2 cm away from target ulcer, on the same lower leg or foot.
4. Target ulcer on the heel.
5. Target ulcer caused primarily by untreated arterial insufficiency or with an etiology not related to diabetes.
6. Subjects with ulcers related to an incompletely healed amputation wound.
7. Acute or chronic osteomyelitis affecting the area of the target ulcer.
8. Any structural deformity of the lower leg or foot under study that would prevent off-loading of the target ulcer, including acute Charcot osteoarthropathy.
9. 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.
10. 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.
11. Use of any topical antimicrobials or enzymatic debridement treatment, to treat the target ulcer within 7 days prior to Visit 1.
12. 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.
13. 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 5 years prior to administration of any study agent).
14. Vasculitis, connective tissue diseases, or any medical conditions known to impair ulcer healing, other than diabetes.
15. Sickle cell disease
16. Clinically significant electrocardiogram (ECG) abnormality, as determined by the Investigator , including but not limited to:
a. QTc≥450 ms in male subject or ≥460 ms in female subject at screening
b. Significant ST-segment-T wave (ST-T) changes or left bundle branch block (LBBB)
17. Any unstable cardiovascular disease, as determined by the Investigator, that renders the subject inappropriate for participating the study, including but not limited to:
a. Has a history of, or concurrent congestive heart failure (CHF) defined by New York Heart Association (NYHA) Classes III or IV.
b. 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.
18. 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).
19. Poor nutritional status (serum albumin < 2.5 g/dL).
20. A history of drug or alcohol abuse that could compromise compliance or safety.
21. Historyofhumanimmunodeficiencyvirus(HIV)infection.
22. Known sensitivity to any component of BB-101 or placebo.
23. Participation in a clinical trial of an investigational drug or device within 30 days of study drug administration.
24. Pregnancy, lactation, or plans to become pregnant within 6 months.
25. 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.
26. History of non-compliance with treatment or clinical visit attendance.
infection is defined by ≥2 classic findings of inflammation or purulence).
2. Presence of cellulitis or gangrene on the lower leg or foot under study.
3. Presence of another open ulcer <2 cm away from target ulcer, on the same lower leg or foot.
4. Target ulcer on the heel.
5. Target ulcer caused primarily by untreated arterial insufficiency or with an etiology not related to diabetes.
6. Subjects with ulcers related to an incompletely healed amputation wound.
7. Acute or chronic osteomyelitis affecting the area of the target ulcer.
8. Any structural deformity of the lower leg or foot under study that would prevent off-loading of the target ulcer, including acute Charcot osteoarthropathy.
9. 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.
10. 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.
11. Use of any topical antimicrobials or enzymatic debridement treatment, to treat the target ulcer within 7 days prior to Visit 1.
12. 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.
13. 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 5 years prior to administration of any study agent).
14. Vasculitis, connective tissue diseases, or any medical conditions known to impair ulcer healing, other than diabetes.
15. Sickle cell disease
16. Clinically significant electrocardiogram (ECG) abnormality, as determined by the Investigator , including but not limited to:
a. QTc≥450 ms in male subject or ≥460 ms in female subject at screening
b. Significant ST-segment-T wave (ST-T) changes or left bundle branch block (LBBB)
17. Any unstable cardiovascular disease, as determined by the Investigator, that renders the subject inappropriate for participating the study, including but not limited to:
a. Has a history of, or concurrent congestive heart failure (CHF) defined by New York Heart Association (NYHA) Classes III or IV.
b. 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.
18. 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).
19. Poor nutritional status (serum albumin < 2.5 g/dL).
20. A history of drug or alcohol abuse that could compromise compliance or safety.
21. Historyofhumanimmunodeficiencyvirus(HIV)infection.
22. Known sensitivity to any component of BB-101 or placebo.
23. Participation in a clinical trial of an investigational drug or device within 30 days of study drug administration.
24. Pregnancy, lactation, or plans to become pregnant within 6 months.
25. 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.
26. History of non-compliance with treatment or clinical visit attendance.
The Estimated Number of Participants
-
Taiwan
12 participants
-
Global
12 participants
