A Study to Evaluate the Efficacy, Safety and Tolerability of CBL-514 Injection for Reducing Subcutaneous Fat (Stage 1)

Study Overview
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Brief Summary
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The Stage 1 of this phase 2 study is an open-label single ascending dose (SAD) study. The primary objectives are to evaluate the safety and tolerability of injection lipolysis with CBL-514. It will be followed by a parallel-arm multiple-dose design in Stage 2.

Official Title
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A 2-Stage Adaptive Design, Phase 2 Study to Evaluate the Efficacy, Safety and Tolerability of CBL-514 Injection for Reducing Abdominal and Thigh Subcutaneous Fat (Stage 1)

Conditions
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Subcutaneous Fat

Intervention / Treatment
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* Drug: CBL-514


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) >18.5 and <32 kg/m2 and body weight ≥50 kg at Screening and Day 1. Subject has sufficient thigh subcutaneous fat thickness of at least 1.50 cm (15.0 mm) and up to 5.00 cm (50.0 mm) measured by ultrasound, surrounding the center of treatment area at Screening and Day 1. Subject has stable body weight (identified as ≤ 5% weight change) for at least 3 months before Screening and during the study. Subject who has maintained a stable lifestyle (e.g. exercise, eating patterns, and smoking habit) for at least 3 months before Screening and during the study. Voluntarily signs the Informed Consent Form (ICF) and, in the opinion of the Investigator or delegate, is physically and mentally capable of participating in the study, and willing to adhere to study procedures. Exclusion Criteria: Female subject of childbearing potential who is not willing to commit to an acceptable contraceptive regimen with her partner from the time of Screening and throughout study participation until 90 days after the last investigational product (IP) dose, or who is currently pregnant or lactating. Male subject who is not willing to commit to an acceptable contraceptive method. Females who have been surgically sterilized (hysterectomy or bilateral oophorectomy) or who are post-menopausal (e.g., defined as at least 50 years with ≥12 months of amenorrhea with a follicle stimulating hormone (FSH) >40 IU/L) are considered to be of non-childbearing potential. Subjects who are not of childbearing potential are not required to use contraception. Subject diagnosed with coagulation disorders or is receiving anticoagulant/antiplatelet therapy or medications or dietary supplements, which impede coagulation or platelet aggregation. Subject has fasting hemoglobin A1c (HbA1c) ≥ 9%, delayed would healing, or any diabetic risks which, in the opinion of Investigator, is inappropriate to participate in the study. Subject has a clinically significant cardiovascular disease and abnormal findings in electrocardiogram (ECG). Subject with active or prior history of malignancies within 5 years before Screening or being worked-up for a possible malignancy. Except adequately treated basal cell carcinoma of skin and in situ squamous cell carcinoma of skin would be eligible as per Investigator's discretion. Subject with a history of human immunodeficiency virus (HIV)-1, infection or subjects with active HIV infection at Screening with positive HIV antigen/antibody (Ag/Ab) combo test. Subjects with any hepatic medical condition that would interfere with assessment of safety or efficacy or compromise the subject's ability to undergo study procedures or provide informed consent. Subject has abnormal skin or local skin conditions at the treatment area, which in the opinion of Investigator, is inappropriate to participate in the study, including but not limited to any of the following: Skin manifestations of a systemic disease, Any abnormality of the skin or soft tissues of the area to be treated, Grade III cellulite (Nürnberger and Muller scale, Nürnberger F, 1978) at the area to be treated, Skin folding on treatment area when the subject is in the supine position, Sensory loss or dysesthesia in the area to be treated, Evidence of any cause of enlargement in the area to be treated other than localized subcutaneous fat, Tattoos on the area to be treated. Subject who has undergone the following procedures: Previous surgery in the anticipated treatment area, Cardiac pacemakers or any implantable electrical device, Metal implants of any type in the area to be treated, Esthetic procedure i.e. liposuction to the region to be treated, Esthetic procedure e.g. cryolipolysis, ultrasonic lipolysis, low level laser therapy (LLLT), lipolysis injection to the region to be treated within 12 months before Screening or during the study. Subject is on prescription or over-the-counter (OTC) weight reduction medication or weight reduction programs within 3 months before Screening or during the study. Subject is undergoing chronic steroid or immunosuppressive therapy. Requiring continual use of the following therapeutic agents during the study: S mephenytoin (Mesantoin), terfenadine (Teldane), buspirone (Buspar), fexofenadine (Fexotabs, Tefodine, Telfast, Xergic, Allegra, etc.). If a subject needs to use the above mentioned therapeutic agents during the study for any reason, these therapeutic agents should not be used at least for 48 hours prior to dosing and until 24 hours post-dose. Unable to receive topical anesthesia (e.g., history of hypersensitivity to Benzocaine, lidocaine, or Tetracaine). Subjects with known allergies or sensitivities to the IP or its components. Subjects with inadequate liver function at Screening defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALKP), total bilirubin (TBIL), or gamma-glutamyl transferase (GGT) >3.0 × upper limit of normal (ULN). Subjects with inadequate renal function, defined as abnormal serum creatinine, and urea >1.5 × ULN or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Subjects who are currently on dialysis should be excluded. Use of other investigational drug or device within 4 weeks prior to Screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBL-514 320 mg<br> | Drug: CBL-514<br>* CBL-514 will be administered via injection into the thigh subcutaneous adipose layer.<br>|
| Experimental: CBL-514 480 mg<br> | Drug: CBL-514<br>* CBL-514 will be administered via injection into the thigh subcutaneous adipose layer.<br>|
| Experimental: CBL-514 640 mg<br> | Drug: CBL-514<br>* CBL-514 will be administered via injection into the thigh subcutaneous adipose layer.<br>|
| Experimental: CBL-514 800 mg<br> | Drug: CBL-514<br>* CBL-514 will be administered via injection into the thigh subcutaneous adipose layer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events (TEAEs) | Number of participants experiencing TEAEs and number of individual TEAEs among treatment groups by severity and relationship to investigational product (IP) | Up to 4 weeks after treatment | 
| Number of participants with clinically significant abnormalities in clinical laboratory values | Clinical laboratory tests include Biochemistry, Hematology, Coagulation and Urinalysis test | Up to 4 weeks after treatment | 
| Number of participants with clinically significant abnormalities in vital signs | Vital signs measurements include temperature, pulse rate, blood pressure, and respiratory rate | Up to 4 weeks after treatment | 
| Number of participants with clinically significant abnormalities in Electrocardiogram (ECG) | ECG parameters include heart rate, RR interval, PR interval, QT interval, QTc interval, and QRS interval | Up to 4 weeks after treatment | 
| Number of participants with clinically significant abnormalities in physical examination | Physical examinations include assessment of cardiovascular, respiratory, gastrointestinal, and neurological systems | Up to 4 weeks after treatment | 
| Number of participants with injection site reactions | Injection site reactions include but not limited to redness, swelling, bruising, tenderness, itching, pain, warmth, discoloration and hardness | Up to 4 weeks after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in thigh subcutaneous fat thickness as measured by ultrasound compared to Baseline |  | Up to 4 weeks after treatment | 
| Change in thigh subcutaneous fat volume over the treated area as measured by ultrasound compared to Baseline |  | Up to 4 weeks after treatment |