Subcutaneous Fat
Conditions
Brief summary
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.
Interventions
DRUGCBL-514
CBL-514 will be administered via injection into the subcutaneous adipose layer.
Sponsors
Caliway Biopharmaceuticals Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
1. Body mass index (BMI) \>18.5 and \<32 kg/m2 and body weight ≥50 kg at Screening and Day 1. 2. 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. 3. Subject has stable body weight (identified as ≤ 5% weight change) for at least 3 months before Screening and during the study. 4. 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. 5. 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 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. 2. Subject diagnosed with coagulation disorders or is receiving anticoagulant/antiplatelet therapy or medications or dietary supplements, which impede coagulation or platelet aggregation. 3. 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. 4. Subject has a clinically significant cardiovascular disease and abnormal findings in electrocardiogram (ECG). 5. 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. 6. 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. 7. 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. 8. 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: 1. Skin manifestations of a systemic disease, 2. Any abnormality of the skin or soft tissues of the area to be treated, 3. Grade III cellulite (Nürnberger and Muller scale, Nürnberger F, 1978) at the area to be treated, 4. Skin folding on treatment area when the subject is in the supine position, 5. Sensory loss or dysesthesia in the area to be treated, 6. Evidence of any cause of enlargement in the area to be treated other than localized subcutaneous fat, 7. Tattoos on the area to be treated. 9. Subject who has undergone the following procedures: 1. Previous surgery in the anticipated treatment area, 2. Cardiac pacemakers or any implantable electrical device, 3. Metal implants of any type in the area to be treated, 4. Esthetic procedure i.e. liposuction to the region to be treated, 5. 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. 10. 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. 11. Subject is undergoing chronic steroid or immunosuppressive therapy. 12. 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. 13. Unable to receive topical anesthesia (e.g., history of hypersensitivity to Benzocaine, lidocaine, or Tetracaine). 14. Subjects with known allergies or sensitivities to the IP or its components. 15. 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). 16. 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. 17. Use of other investigational drug or device within 4 weeks prior to Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Injection Site Reactions | Up to 4 weeks after treatment | Injection site reactions include but not limited to redness, swelling, bruising, tenderness, itching, pain, warmth, discoloration and hardness |
| Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | Up to 4 weeks after treatment | ECG parameters include heart rate, RR interval, PR interval, QT interval, QTc interval, and QRS interval |
| Number of Participants With Clinically Significant Abnormalities in Physical Examination | Up to 4 weeks after treatment | Physical examinations include assessment of cardiovascular, respiratory, gastrointestinal, and neurological systems |
| Number of Treatment Emergent Adverse Events | Up to 4 weeks after treatment | Number of treatment emergent adverse events (TEAEs) |
| Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | Up to 4 weeks after treatment | The clinical laboratory tests include Biochemistry, Hematology, Coagulation and Urinalysis test |
| Number of Participants With Clinically Significant Abnormalities in Vital Signs | Up to 4 weeks after treatment | Vital signs measurements include temperature, pulse rate, blood pressure, and respiratory rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Subcutaneous Fat Volume | Up to 4 weeks after treatment | Change in subcutaneous fat volume over the treated area as measured by ultrasound compared to Baseline. No efficacy assessments were done for Group 1 of Stage 1 study. |
| Change in Subcutaneous Fat Thickness | Up to 4 weeks after treatment | Change in subcutaneous fat thickness as measured by ultrasound compared to Baseline. No efficacy assessments were done for Group 1 of Stage 1 study. |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CBL-514 320 mg CBL-514 will be administered via injection into the thigh subcutaneous adipose layer. | 6 |
| CBL-514 480 mg CBL-514 will be administered via injection into the abdomen subcutaneous adipose layer. | 7 |
| CBL-514 640 mg CBL-514 will be administered via injection into the abdomen subcutaneous adipose layer. | 6 |
| CBL-514 800 mg CBL-514 will be administered via injection into the abdomen subcutaneous adipose layer. | 6 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | CBL-514 320 mg | CBL-514 480 mg | CBL-514 640 mg | CBL-514 800 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 52.5 years | 48 years | 31.5 years | 51.5 years | 51 years |
| Body Mass Index | 26.08 kg/m2 STANDARD_DEVIATION 1.95 | 25.16 kg/m2 STANDARD_DEVIATION 2.51 | 26.15 kg/m2 STANDARD_DEVIATION 3.74 | 25.97 kg/m2 STANDARD_DEVIATION 2.66 | 25.81 kg/m2 STANDARD_DEVIATION 2.64 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 7 Participants | 5 Participants | 6 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 5 Participants | 4 Participants | 4 Participants | 19 Participants |
| Region of Enrollment Australia | 6 Participants | 7 Participants | 6 Participants | 6 Participants | 25 Participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 6 Participants | 3 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 5 Participants |
| Weight | 69.46 kg STANDARD_DEVIATION 7.58 | 75.25 kg STANDARD_DEVIATION 12.7 | 65.93 kg STANDARD_DEVIATION 9.01 | 75.48 kg STANDARD_DEVIATION 5.8 | 71.68 kg STANDARD_DEVIATION 9.65 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 6 / 6 | 7 / 7 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 | 1 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values
The clinical laboratory tests include Biochemistry, Hematology, Coagulation and Urinalysis test
Time frame: Up to 4 weeks after treatment
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CBL-514 320 mg | Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | 0 Participants |
| CBL-514 480 mg | Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | 0 Participants |
| CBL-514 640 mg | Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | 0 Participants |
| CBL-514 800 mg | Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values | 1 Participants |
Primary
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
Time frame: Up to 4 weeks after treatment
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CBL-514 320 mg | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| CBL-514 480 mg | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| CBL-514 640 mg | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
| CBL-514 800 mg | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | 0 Participants |
Primary
Number of Participants With Clinically Significant Abnormalities in Physical Examination
Physical examinations include assessment of cardiovascular, respiratory, gastrointestinal, and neurological systems
Time frame: Up to 4 weeks after treatment
Population: ITT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CBL-514 320 mg | Number of Participants With Clinically Significant Abnormalities in Physical Examination | 0 Participants |
| CBL-514 480 mg | Number of Participants With Clinically Significant Abnormalities in Physical Examination | 0 Participants |
| CBL-514 640 mg | Number of Participants With Clinically Significant Abnormalities in Physical Examination | 0 Participants |
| CBL-514 800 mg | Number of Participants With Clinically Significant Abnormalities in Physical Examination | 0 Participants |
Primary
Number of Participants With Clinically Significant Abnormalities in Vital Signs
Vital signs measurements include temperature, pulse rate, blood pressure, and respiratory rate
Time frame: Up to 4 weeks after treatment
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CBL-514 320 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| CBL-514 480 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| CBL-514 640 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
| CBL-514 800 mg | Number of Participants With Clinically Significant Abnormalities in Vital Signs | 0 Participants |
Primary
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
Time frame: Up to 4 weeks after treatment
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CBL-514 320 mg | Number of Participants With Injection Site Reactions | 6 Participants |
| CBL-514 480 mg | Number of Participants With Injection Site Reactions | 7 Participants |
| CBL-514 640 mg | Number of Participants With Injection Site Reactions | 6 Participants |
| CBL-514 800 mg | Number of Participants With Injection Site Reactions | 6 Participants |
Primary
Number of Treatment Emergent Adverse Events
Number of treatment emergent adverse events (TEAEs)
Time frame: Up to 4 weeks after treatment
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CBL-514 320 mg | Number of Treatment Emergent Adverse Events | 103 number of events |
| CBL-514 480 mg | Number of Treatment Emergent Adverse Events | 57 number of events |
| CBL-514 640 mg | Number of Treatment Emergent Adverse Events | 69 number of events |
| CBL-514 800 mg | Number of Treatment Emergent Adverse Events | 61 number of events |
Secondary
Change in Subcutaneous Fat Thickness
Change in subcutaneous fat thickness as measured by ultrasound compared to Baseline. No efficacy assessments were done for Group 1 of Stage 1 study.
Time frame: Up to 4 weeks after treatment
Population: ITT Population (Data not collected for participants that received the 320 mg injection)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBL-514 320 mg | Change in Subcutaneous Fat Thickness | -4.77 Absolute Change (mm) from Baseline | Standard Deviation 2.29 |
| CBL-514 480 mg | Change in Subcutaneous Fat Thickness | -4.85 Absolute Change (mm) from Baseline | Standard Deviation 2.02 |
| CBL-514 640 mg | Change in Subcutaneous Fat Thickness | -2.98 Absolute Change (mm) from Baseline | Standard Deviation 2.83 |
p-value: <0.0195% CI: [-7.17, -2.37]Paired t-test
p-value: <0.0195% CI: [-6.97, -2.73]Paired t-test
p-value: <0.0595% CI: [-5.95, -0.01]Paired t-test
Secondary
Change in Subcutaneous Fat Volume
Change in subcutaneous fat volume over the treated area as measured by ultrasound compared to Baseline. No efficacy assessments were done for Group 1 of Stage 1 study.
Time frame: Up to 4 weeks after treatment
Population: ITT Population (Data not collected for participants that received the 320 mg injection)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBL-514 320 mg | Change in Subcutaneous Fat Volume | -114.40 Absolute change (mL) from Baseline | Standard Deviation 54.88 |
| CBL-514 480 mg | Change in Subcutaneous Fat Volume | -155.20 Absolute change (mL) from Baseline | Standard Deviation 64.7 |
| CBL-514 640 mg | Change in Subcutaneous Fat Volume | -119.17 Absolute change (mL) from Baseline | Standard Deviation 113.11 |
p-value: <0.0195% CI: [-171.99, -56.81]Paired t-test
p-value: <0.0195% CI: [-223.1, -87.3]Paired t-test
p-value: <0.0595% CI: [-237.86, -0.47]Paired t-test