A Study to Evaluate the Efficacy, Safety and Tolerability of CBL-514 Injection for Reducing Abdominal Subcutaneous Fat

A Randomized, Placebo-Controlled, Phase 2b Study to Evaluate the Efficacy, Safety and Tolerability of CBL-514 Injection for Reducing Abdominal Subcutaneous Fat

This is a randomized, placebo-controlled, Phase 2b study to evaluate the efficacy, safety, and tolerability of CBL-514 injection for reducing subcutaneous fat.

Study Overview

• Status: Active, not recruiting
• Conditions: Subcutaneous Fat
• Intervention / Treatment: Drug: CBL-514 Injection; Other: 0.9% Sodium Chloride

Detailed Description

A total of approximately 110 adult participants with moderate or severe abdominal fat as assessed by the Investigator via live evaluation using the Clinician-Reported Abdominal Fat Rating Scale (CR-AFRS) at Screening will be enrolled. Each participant will receive up to 4 treatments of allocated CBL-514 (2 mg/cm²) or placebo administered subcutaneously to the abdomen, once every 3 weeks.

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Pflugerville, Texas, United States, 78660
      • Investigational Site 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male or female, aged 18 years to 64 years old (at Screening), inclusive.
2. Body mass index (BMI) > 18.5 and < 30 kg/m2 and body weight ≥ 50 kg at Screening and Day 1.
3. Participant has abdominal fat graded by the Investigator as Grade 3 (moderate) or Grade 4 (severe) using the Clinician-Reported Abdominal Fat Rating Scale via live evaluation at Screening.
4. Participant has stable body weight (identified as ≤ 3 kg weight change per participant report) for at least 3 months before Screening and during the study.
5. Participant who has maintained a stable lifestyle (e.g., exercise, eating patterns, and smoking habit) per participant report for at least 3 months before Screening and during the study.
6. 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:

1. Female participant of childbearing potential who is not willing to commit to an acceptable contraceptive regimen from the time of Screening and throughout study participation until 90 days after the last IP dose, or who is currently pregnant or lactating. Male participant who is not willing to commit to using of a condom and refraining from sperm donation from the time of the first dose of IP, throughout study participation until 90 days after the last IP dose.

   Note: Participants who are not of childbearing potential are not required to use contraception. Females not of childbearing potential are defined as those who have been surgically sterilized (hysterectomy or bilateral oophorectomy) or who are post-menopausal (defined as at least 50 years of age with greater than or equal to 12 months of amenorrhea with a follicle stimulating hormone (FSH) greater than 30 IU/L).

2. Participant diagnosed with coagulation disorders or who is receiving anticoagulant/antiplatelet therapy or medications or dietary supplements that impede coagulation or platelet aggregation.
3. Participant has hemoglobin A1c (HbA1c) greater than or equal to 9%, delayed wound healing, or poorly controlled diabetes defined as requiring a change in glucose control medications (other than day to day variations in insulin requirements) within the 6 months prior to Screening or for whom a change in glucose control medications is anticipated during the study, or any diabetic risks that, in the opinion of Investigator, make the individual an inappropriate candidate for the study.
4. Participant with active or prior history of malignancies within 5 years before Screening or currently being evaluated for a possible malignancy, with the exception of adequately treated basal cell carcinoma of skin and in situ squamous cell carcinoma of skin at Investigator's discretion.
5. Participant with a history of human immunodeficiency virus (HIV)-1 infection or participant with active HIV infection at Screening with positive HIV antigen/antibody (Ag/Ab) combo test.
6. Participant with a history of trypanophobia, the extreme fear of medical procedures involving injections or needles, or who experiences vasovagal syncope and faints at the sight of blood or a needle.
7. Participant with folding fat or skin on abdomen in standing position.
8. Participant with severe or very severe abdominal visceral fat assessed by the Investigator using the visceral fat scale.
9. Participant with ventral abdominal or umbilical hernia or previous repair of same.

10. Participant has abnormal skin or local skin conditions at the treatment area, which, in the opinion of Investigator, would increase risk to the participant or inhibit safety or efficacy evaluation, including but not limited to any of the following:

    1. Skin manifestations of a systemic disease,
    2. Any abnormality of the skin or soft tissues of the area to be treated, such as scars, striae, dyspigmentation, etc.,
    3. Asymmetrical fat on abdomen,
    4. Lipomatosis syndromes (familial lipomatosis, nevus lipomatosis, Dercum's disease, etc.),
    5. Skin laxity on abdomen,
    6. Sensory loss or dysesthesia in the area to be treated,
    7. Tattoo(s) on the front and/or lateral side of abdomen.

11. Participant who has undergone the following procedures:

    1. Previous surgery that caused scar tissues on the anticipated treatment area before Screening or during the study, with the exception of laparoscopic surgery and surgery that resulted in minimal scar tissue determined at Investigator's discretion,
    2. Liposuction or abdominoplasty to the region to be treated before Screening or during the study,
    3. Aesthetic procedure for body contouring or fat reduction, e.g., cryolipolysis, ultrasonic lipolysis, low level laser therapy, EMSculpt, lipolysis injection to the region to be treated within 12 months before Screening or during the study.
    4. Using medication that is delivered via subcutaneous injection at the treatment area within 4 weeks before Screening or during the study.
12. Participant is on prescription or OTC weight reduction medication, weight reduction programs, or use of any GLP-1 agonists (e.g., semaglutide, terzepatide, liraglutide, etc.) (oral or injectable) within 6 months before Screening or during the study.
13. Participant is undergoing chronic steroid or immunosuppressive therapy, with the exception of oral steroid inhalation indicated for asthma management or topical steroid application for skin conditions that are not directly applied to or indirectly affect the treatment area.

14. Requiring continual use of any medication that is known to strongly inhibit or induce CYP1A2 enzymes, sensitive CYP1A2 substrates or drugs with narrow therapeutic index during the study that, in the opinion of the Investigator, may affect the evaluation of the study product or place the participant at undue risk.

    Note: If a participant needs to use the above mentioned therapeutic agents during the study for any reason, these therapeutic agents should not be used at least for 2 days prior to dosing and until 1 day post-dose.

15. Unable to receive local anesthesia (e.g., history of hypersensitivity to lidocaine).
16. Participant with known allergies or sensitivities to the IP or its components, medical history of urticaria, any drug allergy, or seasonal allergy that presents with skin-related symptoms. Participant with food allergies can be enrolled at the discretion of Investigator.
17. Participant with liver cirrhosis, with inadequate liver function at Screening defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin (TBIL), or gamma-glutamyl transferase (GGT) greater than 3.0 × upper limit of normal (ULN), or with any hepatic medical condition that would interfere with assessment of safety or efficacy.

18. Participant with any renal impairment, defined as:

    1. serum creatinine greater than 1.5 × ULN and blood urea nitrogen (BUN) greater than 1.5 × ULN, or
    2. estimated glomerular filtration rate (eGFR) less than 90 mL/min/1.73 m2, or who is currently on dialysis.

    Note: Participant with an eGFR greater than or equal to 60 and less than 90 mL/min/1.73 m2 at Screening should be evaluated by the Investigator for pre-existing disease or associated dysfunction. If mild decrease in eGFR is deemed not clinically significant or not related to dysfunction by the Investigator, the participant will not be excluded unless the Investigator deems it necessary.

19. Participant with contraindications to MRI imaging.
20. Use of any investigational drug or device within 3 months prior to Screening.

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
Experimental: CBL-514 Injection; Participant will receive CBL-514 2 mg/cm² administered in 2.4 mL injections, up to 120 mL per treatment session at intervals of approximately 3 weeks for up to a maximum of 4 treatments.	Drug: CBL-514 Injection; Formulated as an injectable CBL-514 solution at a concentration of 5 mg/mL.
Placebo Comparator: 0.9% Sodium Chloride; Participant will receive 0.9% Sodium Chloride administered in 2.4 mL injections, up to 120 mL per treatment session at intervals of approximately 3 weeks for up to a maximum of 4 treatments.	Other: 0.9% Sodium Chloride; Sodium Chloride (0.9% NaCl) placebo for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with at least 1-grade improvement reported by Investigator via photographic evaluation using the Clinician-Reported Abdominal Fat Rating Scale (CR-AFRS)	Percentage of participants with at least 1-grade improvement reported by Investigator via photographic evaluation using the Clinician-Reported Abdominal Fat Rating Scale (CR-AFRS) compared with placebo. Note: The AFRS is a 5-point ordinal scale (0-5) to assess the abdominal fat level based on the presence of fat on abdomen with 1=None/Minimal, 2=Mild, 3=Moderate, 4=Severe and 5=Very Severe.	From baseline to 8 weeks after the final treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with at least 1-grade improvement reported by Investigator via photographic evaluation using CR-AFRS	Percentage of participants with at least 1-grade improvement reported by Investigator via photographic evaluation using CR-AFRS compared with placebo. Note: The AFRS is a 5-point ordinal scale (0-5) to assess the abdominal fat level based on the presence of fat on abdomen with 1=None/Minimal, 2=Mild, 3=Moderate, 4=Severe and 5=Very Severe.	From baseline to 4 weeks and 12 weeks after the final treatment
Percentage of participants with at least 2-grade improvement reported by Investigator via photographic evaluation using CR-AFRS	Percentage of participants with at least 2-grade improvement reported by Investigator via photographic evaluation using CR-AFRS compared with placebo. Note: The AFRS is a 5-point ordinal scale (0-5) to assess the abdominal fat level based on the presence of fat on abdomen with 1=None/Minimal, 2=Mild, 3=Moderate, 4=Severe and 5=Very Severe.	From baseline to 4 weeks, 8 weeks, and 12 weeks after the final treatment
Percentage of participants with at least 1-grade improvement reported by blinded physicians using CR-AFRS	Percentage of participants with at least 1-grade improvement reported by blinded physicians using CR-AFRS compared with placebo. Note: The AFRS is a 5-point ordinal scale (0-5) to assess the abdominal fat level based on the presence of fat on abdomen with 1=None/Minimal, 2=Mild, 3=Moderate, 4=Severe and 5=Very Severe.	From baseline to 4 weeks, 8 weeks and 12 weeks after the final treatment
Percentage of participants with at least 2-grade improvement reported by blinded physicians using CR-AFRS	Percentage of participants with at least 2-grade improvement reported by blinded physicians using CR-AFRS compared with placebo. Note: The AFRS is a 5-point ordinal scale (0-5) to assess the abdominal fat level based on the presence of fat on abdomen with 1=None/Minimal, 2=Mild, 3=Moderate, 4=Severe and 5=Very Severe.	From baseline to 4 weeks, 8 weeks and 12 weeks after the final treatment
Percentage of participants with at least 1-grade improvement reported by participant using the Patient-Reported Abdominal Fat Rating Scale (PR-AFRS)	Percentage of participants with at least 1-grade improvement reported by participant using the Patient-Reported Abdominal Fat Rating Scale (PR-AFRS) compared with placebo. Note: The AFRS is a 5-point ordinal scale (0-5) to assess the abdominal fat level based on the presence of fat on abdomen with 1=None/Minimal, 2=Mild, 3=Moderate, 4=Severe and 5=Very Severe.	From baseline to 4 weeks, 8 weeks and 12 weeks after the final treatment
Percentage of participants with at least 2-grade improvement reported by participant using PR-AFRS	Percentage of participants with at least 2-grade improvement reported by participant using PR-AFRS compared with placebo. Note: The AFRS is a 5-point ordinal scale (0-5) to assess the abdominal fat level based on the presence of fat on abdomen with 1=None/Minimal, 2=Mild, 3=Moderate, 4=Severe and 5=Very Severe.	From baseline to 4 weeks, 8 weeks and 12 weeks after the final treatment
Number of treatments required to first occurrence of a CR-AFRS improvement reported by blinded physicians.	Number of treatments required to first occurrence of a CR-AFRS improvement reported by blinded physicians. Note: The AFRS is a 5-point ordinal scale (0-5) to assess the abdominal fat level based on the presence of fat on abdomen with 1=None/Minimal, 2=Mild, 3=Moderate, 4=Severe and 5=Very Severe.	From baseline to 12 weeks after the final treatment
Percentage of participant who lose at least 150 mL of subcutaneous fat volume measured by MRI	Percentage of participant who lose at least 150 mL of subcutaneous fat volume measured by MRI compared with placebo	From baseline to 4 weeks and 12 weeks after the final treatment
Percentage of participant who lose at least 20% of subcutaneous fat volume compared to baseline measured by MRI	Percentage of participant who lose at least 20% of subcutaneous fat volume compared to baseline measured by MRI compared with placebo	From baseline to 4 weeks and 12 weeks after the final treatment
Percentage of participant who lose at least 25% of subcutaneous fat volume compared to baseline measured by MRI	Percentage of participant who lose at least 25% of subcutaneous fat volume compared to baseline measured by MRI compared with placebo	From baseline to 4 weeks and 12 weeks after the final treatment
Reduction of subcutaneous fat volume measured by MRI	Reduction of subcutaneous fat volume compared to baseline measured by MRI	From baseline to 4 weeks and 12 weeks after the final treatment
The percentage change in subcutaneous fat volumemeasured by MRI	The percentage change in subcutaneous fat volume compared to baseline measured by MRI	From baseline to 4 weeks and 12 weeks after the final treatment
Percentage of participant who lose at least 20 % of subcutaneous fat thickness compared to baseline measured by MRI	Percentage of participant who lose at least 20 % of subcutaneous fat thickness compared to baseline measured by MRI compared with placebo	From baseline to 4 weeks and 12 weeks after the final treatment
Percentage of participant who lose at least 25 % of subcutaneous fat thickness compared to baseline measured by MRI	Percentage of participant who lose at least 25 % of subcutaneous fat thickness compared to baseline measured by MRI compared with placebo	From baseline to 4 weeks and 12 weeks after the final treatment
Reduction of subcutaneous fat thickness measured by MRI	Reduction of subcutaneous fat thickness compared to baseline measured by MRI	From baseline to 4 weeks and 12 weeks after the final treatment
The percentage change in subcutaneous fat thickness measured by MRI	The percentage change in subcutaneous fat thickness compared to baseline measured by MRI	From baseline to 4 weeks and 12 weeks after the final treatment

Other 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	From baseline to 12 weeks after the final treatment
Incidence of clinically significant abnormal findings	Number of participants with clinically significant abnormalities in laboratory tests, vital signs and physical examinations	From baseline to 12 weeks after the final treatment
Percentage of participants with at least 1-grade improvement reported by Investigator via live evaluation using CR-AFRS	Percentage of participants with at least 1-grade improvement reported by Investigator via live evaluation using CR-AFRS compared with placebo.	From baseline to 12 weeks after the final treatment
Percentage of participants with at least 2-grade improvement reported by Investigator via live evaluation using CR-AFRS	Percentage of participants with at least 2-grade improvement reported by Investigator via live evaluation using CR-AFRS compared with placebo.	From baseline to 12 weeks after the final treatment

Collaborators and Investigators

• Sponsor: Caliway Biopharmaceuticals Co., Ltd.
• Investigators: Study Director: Anne Sheu, Caliway Biopharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2023
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: February 10, 2023
• First Submitted That Met QC Criteria: February 10, 2023
• First Posted (Actual): February 21, 2023

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: CBL-0204

Drug and device information, study documents

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