A Phase 2b Study to Evaluate the Efficacy and Safety of CBL-514 Injection for Reducing Subcutaneous Fat.

• ClinicalTrials.gov Identifier: NCT06005441
• Recruitment Status: Recruiting
• First Posted: August 22, 2023
• Last Update Posted: February 6, 2024
• Sponsor: Caliway Biopharmaceuticals Co., Ltd.
• Information provided by (Responsible Party): Caliway Biopharmaceuticals Co., Ltd.

Tracking Information

• First Submitted Date: August 10, 2023
• First Posted Date: August 22, 2023
• Last Update Posted Date: February 6, 2024
• Actual Study Start Date: November 10, 2023
• Estimated Primary Completion Date: September 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 17, 2023)

Percentage of participants with at least 150 mL reduction in abdominal subcutaneous fat volume from Baseline to 8 weeks after the final treatment [ Time Frame: From Baseline to 8 weeks after the final treatment ]

Percentage of participants with at least 150 mL reduction in abdominal subcutaneous fat volume from Baseline to 8 weeks after the final treatment, as measured by MRI, of CBL-514 compared with CBL-A1, CBL-A2, and placebo.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 2, 2024)

• Mean change in abdominal subcutaneous fat volume from Baseline to 4 weeks and 8 weeks after the final treatment [ Time Frame: From Baseline to 4 weeks and 8 weeks after the final treatment ]
  Mean change in abdominal subcutaneous fat volume from Baseline to 4 weeks and 8 weeks after the final treatment, as measured by MRI, of CBL-514 compared with CBL-A1, CBL-A2, and placebo.
• Percentage of participants with at least 150 mL reduction in abdominal subcutaneous fat volume from Baseline to 4 weeks after the final treatment [ Time Frame: From Baseline to 4 weeks after the final treatment ]
  Percentage of participants with at least 150 mL reduction in abdominal subcutaneous fat volume from Baseline to 4 weeks after the final treatment, as measured by MRI, of CBL-514 compared with CBL-A1, CBL-A2, and placebo.
• Percentage of participants with at least 200 mL reduction in abdominal subcutaneous fat volume from Baseline to 4 weeks and 8 weeks after the final treatment [ Time Frame: From Baseline to 4 weeks and 8 weeks after the final treatment ]
  Percentage of participants with at least 200 mL reduction in abdominal subcutaneous fat volume from Baseline to 4 weeks and 8 weeks after the final treatment, as measured by MRI, of CBL-514 compared with CBL-A1, CBL-A2, and placebo.
• Percentage of participants with at least 1-grade improvement reported by the Investigator using the Clinician-Reported Abdominal Fat Rating Scale (CR-AFRS) via examining the participants in-person at 4 weeks and 8 weeks after the final treatment [ Time Frame: From Baseline to 4 weeks and 8 weeks after the final treatment ]
  Percentage of participants with at least 1-grade improvement reported by the Investigator using the Clinician-Reported Abdominal Fat Rating Scale (CR-AFRS) via examining the participants in-person at 4 weeks and 8 weeks after the final treatment, for CBL-514 compared with CBL-A1, CBL-A2, and 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.
• Percentage of participants with at least 1-grade improvement reported by the Investigator using the Clinician-Reported Abdominal Fat Rating Scale (CR-AFRS) via photo-based system at 4 weeks and 8 weeks after the final treatment [ Time Frame: From Baseline to 4 weeks and 8 weeks after the final treatment ]
  Percentage of participants with at least 1-grade improvement reported by the Investigator using the Clinician-Reported Abdominal Fat Rating Scale (CR-AFRS) via photo-based system at 4 weeks and 8 weeks after the final treatment, for CBL-514 compared with CBL-A1, CBL-A2, and 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.
• Percentage of participants with at least 1-grade improvement reported by the participant using the Patient-Reported Abdominal Fat Rating Scale (PR-AFRS) via examining self-abdomen in the mirror at 4 weeks and 8 weeks after the final treatment. [ Time Frame: From Baseline to 4 weeks and 8 weeks after the final treatment ]
  Percentage of participants with at least 1-grade improvement reported by the participant using the Patient-Reported Abdominal Fat Rating Scale (PR-AFRS) via examining self-abdomen in the mirror at 4 weeks and 8 weeks after the final treatment, for CBL-514 compared with CBL-A1, CBL-A2, and 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.
• Percentage of participants with at least 1-grade improvement reported by the participant using the Patient-Reported Abdominal Fat Rating Scale (PR-AFRS) via photo-based system at 4 weeks and 8 weeks after the final treatment. [ Time Frame: From Baseline to 4 weeks and 8 weeks after the final treatment ]
  Percentage of participants with at least 1-grade improvement reported by the participant using the Patient-Reported Abdominal Fat Rating Scale (PR-AFRS) via photo-based system at 4 weeks and 8 weeks after the final treatment, for CBL-514 compared with CBL-A1, CBL-A2, and 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.
• The incidence of treatment-emergent adverse events (TEAEs) as defined in the protocol [ Time Frame: From Baseline to 8 weeks after the final treatment ]
  Number of participants experiencing TEAEs and number of individual TEAEs
• The incidence of clinically significant abnormal findings as defined in the protocol [ Time Frame: From Baseline to 8 weeks after the final treatment ]
  Number of participants with clinically significant abnormalities in laboratory tests, vital signs and physical examinations

Original Secondary Outcome Measures (submitted: August 17, 2023)

• Mean change in abdominal subcutaneous fat volume from Baseline to 4 weeks and 8 weeks post the final treatment [ Time Frame: From Baseline to 4 weeks and 8 weeks after the final treatment ]
  Mean change in abdominal subcutaneous fat volume from Baseline to 4 weeks and 8 weeks post the final treatment, as measured by MRI, of CBL-514 compared with CBL-A1, CBL-A2, and placebo.
• Percentage of participants with at least 150 mL reduction in abdominal subcutaneous fat volume from Baseline to 4 weeks after the final treatment [ Time Frame: From Baseline to 4 weeks after the final treatment ]
  Percentage of participants with at least 150 mL reduction in abdominal subcutaneous fat volume from Baseline to 4 weeks after the final treatment, as measured by MRI, of CBL-514 compared with CBL-A1, CBL-A2, and placebo.
• Percentage of participants with at least 200 mL reduction in abdominal subcutaneous fat volume from Baseline to 4 weeks and 8 weeks after the final treatment [ Time Frame: From Baseline to 4 weeks and 8 weeks after the final treatment ]
  Percentage of participants with at least 200 mL reduction in abdominal subcutaneous fat volume from Baseline to 4 weeks and 8 weeks after the final treatment, as measured by MRI, of CBL-514 compared with CBL-A1, CBL-A2, and placebo.
• Percentage of participants with at least 1-grade improvement reported by the Investigator using the Clinician-Reported Abdominal Fat Rating Scale (CR-AFRS) at 4 weeks and 8 weeks after the final treatment [ Time Frame: From Baseline to 4 weeks and 8 weeks after the final treatment ]
  Percentage of participants with at least 1-grade improvement reported by the Investigator using the Clinician-Reported Abdominal Fat Rating Scale (CR-AFRS) at 4 weeks and 8 weeks after the final treatment, for CBL-514 compared with CBL-A1, CBL-A2, and 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.
• Percentage of participants with at least 1-grade improvement reported by the participant using the Patient-Reported Abdominal Fat Rating Scale (PR-AFRS) at 4 weeks and 8 weeks after the final treatment. [ Time Frame: From Baseline to 4 weeks and 8 weeks after the final treatment ]
  Percentage of participants with at least 1-grade improvement reported by the participant using the Patient-Reported Abdominal Fat Rating Scale (PR-AFRS) at 4 weeks and 8 weeks after the final treatment, for CBL-514 compared with CBL-A1, CBL-A2, and 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.
• Percentage of participants with at least 1-grade improvement reported by the independent clinician using the Clinician-Reported Abdominal Fat Rating Scale (CR-AFRS) at 4 weeks and 8 weeks after the final treatment. [ Time Frame: From Baseline to 4 weeks and 8 weeks after the final treatment ]
  Percentage of participants with at least 1-grade improvement reported by the independent clinician using the Clinician-Reported Abdominal Fat Rating Scale (CR-AFRS) at 4 weeks and 8 weeks after the final treatment, for CBL-514 compared with CBL-A1, CBL-A2, and 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.
• The incidence of treatment-emergent adverse events (TEAEs) as defined in the protocol [ Time Frame: From Baseline to 8 weeks after the final treatment ]
  Number of participants experiencing TEAEs and number of individual TEAEs
• The incidence of clinically significant abnormal findings as defined in the protocol [ Time Frame: From Baseline to 8 weeks after the final treatment ]
  Number of participants with clinically significant abnormalities in laboratory tests, vital signs and physical examinations

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 2b Study to Evaluate the Efficacy and Safety of CBL-514 Injection for Reducing Subcutaneous Fat.
• Official Title: A Phase 2b, Randomized, Placebo-Controlled Factorial Study to Evaluate the Efficacy, Safety and Tolerability of CBL-514 Injection Compared With CBL-A1 and CBL-A2 for Reducing Abdominal Subcutaneous Fat
• Brief Summary: This is a randomized, placebo-controlled, Phase 2b study to evaluate the efficacy, safety, and tolerability of CBL-514 injection compared with CBL-A1 and CBL-A2 for reducing subcutaneous fat.
• Detailed Description: A total of approximately 160 adult participants with moderate or severe abdominal fat at Screening will be enrolled. Each participant will receive up to 4 treatments of allocated study drug administered subcutaneously to the abdomen, once every 3 weeks.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Subcutaneous Fat

Intervention

• Drug: CBL-514 injection
  Provided as a ready for use injectable CBL-514 solution
• Drug: CBL-A1 Injection
  Provided as a ready for use injectable CBL-A1 solution
• Drug: CBL-A2 Injection
  Provided as a ready for use injectable CBL-A2 solution
• Drug: 0.9% Sodium Chloride
  Sodium Chloride (0.9% NaCl) placebo for injection

Study Arms

• Experimental: CBL-514 Injection
  Participant will receive CBL-514 administered in 2.4 mL injections, up to 120 mL per treatment session at intervals of approximately 3 weeks for up to 4 treatments.
  Intervention: Drug: CBL-514 injection
• Experimental: CBL-A1 Injection
  Participant will receive CBL-A1 administered in 2.4 mL injections, up to 120 mL per treatment session at intervals of approximately 3 weeks for up to 4 treatments.
  Intervention: Drug: CBL-A1 Injection
• Experimental: CBL-A2 Injection
  Participant will receive CBL-A2 administered in 2.4 mL injections, up to 120 mL per treatment session at intervals of approximately 3 weeks for up to 4 treatments.
  Intervention: Drug: CBL-A2 Injection
• 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 4 treatments.
  Intervention: Drug: 0.9% Sodium Chloride

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 17, 2023): 160
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2024
• Estimated Primary Completion Date: September 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male or female, aged 18 years to 64 years old (at Screening), inclusive.
2. Body mass index (BMI) >18.5 and < 27 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 in-person examination 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 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 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.
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) ≥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 active HIV infection at Screening with positive HIV antigen/antibody combo test.
6. Participant with a history of trypanophobia, the extreme fear of medical procedures involving injections or needles, or who experiences vasovagal syncope or 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 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 and 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 tissues 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 with contraindications to MRI imaging
13. Participant is on prescription or OTC weight reduction medication, weight reduction program, or any GLP-1 agonist (e.g., semaglutide, terzepatide, liraglutide, etc.) (oral or injectable) within 6 months before Screening or during the study.
14. 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 or indirectly affect the treatment area.
15. 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.
16. Unable to receive local anesthesia.
17. Participant with known allergies or sensitivities to the IP or its components.
18. Participant with liver cirrhosis, with inadequate liver function at Screening defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase(ALP), total bilirubin (TBIL), or gamma-glutamyl transferase (GGT) >3.0× upper limit of normal (ULN), or with any hepatic medical condition that would interfere with assessment of safety or efficacy.
19. Participant with any renal impairment, defined as abnormal serum creatinine and blood urea nitrogen (BUN) >1.5× ULN or estimated glomerular filtration rate (eGFR) <90mL/min/1.73 m2, or who is currently on dialysis.
20. Use of any investigational drug or device within 3 months prior to Screening.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 64 Years (Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Shannon Wu; +886-2-26971355 ext 1316; CR@caliway.com.tw

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT06005441
• Other Study ID Numbers: CBL-0205
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Caliway Biopharmaceuticals Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Caliway Biopharmaceuticals Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Caliway Biopharmaceuticals Co., Ltd.
• Verification Date: February 2024