Intralesional Ronkyla Plus Injection for the Treatment of Superficial Lipoma

Part I is a randomized, double-blind, placebo-controlled, and sequential dose-escalation study. Eligible subjects will receive intralesional injections of Ronkyla Plus or placebo at a volume dependent on the size of their superficial lipoma, up to a maximum of 10 mL per treatment, at 28-day intervals for up to a maximum of 6 treatments. In the first treatment cycle, subjects will stay in hospital for 3 hours after treatment for evaluation of acute safety profile. Subjects will return to the hospital on Day 8 and Day 29 of each treatment cycle for safety profile evaluation.

Part II is an open-label, single-dose, 2-treatment, parallel study to evaluate the relative bioavailability of Ronkyla Plus injection in comparison with that of Kybella injection. Eligible, non-smoking males and females aged 18 to 65 with treatable superficial lipoma or submental fullness will be included in the study. Twenty (20) subjects for each target symptom, in a total of 40 subjects, are planned to be enrolled in the study to achieve at least 16 evaluable subjects in each treatment group. After screening, subjects will be assigned to Ronkyla Plus or Kybella treatment based on their symptoms and undergo a 16-day PK assessment.

For Ronkyla Plus injection, subject will receive a single intralesional treatment at the maximum tolerated dose (MTD) as determined in Part I. For Kybella injection, subject will receive the maximum dose approved for a single treatment (100 mg) in the submental area.

In the PK assessment period, subjects will visit the hospital in the mornings of Day 3 (48.0 h), Day 5 (96.0 h), Day 8 (168.0 h), Day 11 (240.0 h), and Day 15 (336.0 h), and two consecutive 24-hr PK blood samplings from Day -2 evening to Day 2 morning (pre-dose, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0 h post-dose on Day 1~Day 2; same blood sampling time on Day -1~Day 1 without dosing). Two weeks after the end of the 16-day PK assessment period, subjects of Ronkyla Plus cohort will be eligible for up to 5 additional treatments of Ronkyla Plus for complete clearance of their target superficial lipomas, whereas subjects of Kybella cohort will be eligible for up to 5 additional treatments of Ronkyla (10.56 mg/mL SDC injection approved in Taiwan for submental fullness treatment, pharmaceutical equivalent of Kybella) for improvement of their submental fullness.

Inclusion criteria

• Healthy male or female adults aged 18 to 65 years, inclusive.
• One or more superficial lipomas, based on clinical diagnosis, which are accessible for treatment and assessment, are quantifiable along at least 2 perpendicular diameters, and have the following characteristics:

• History of slow growth followed by dormancy, and stable for at least 6 months.
• Greatest length by greatest perpendicular width between 1 and 10 square centimeters, inclusive.
• Discrete, oval to rounded in shape, not hard or attached to underlying tissue.
• Located on the trunk, arms, legs, or neck
• Needle biopsy core tissue sample histological analysis results consistent with a diagnosis of lipoma.

OR, sufficient submental fat for injection of 100 mg Kybella in the judgment of the investigator (Part II Kybella cohort only)

• Body mass index (BMI): BMI between 22 to 30 (normal, overweight and slight obese).
• History of stable body weight, in the judgment of the investigator, for at least 6 months before enrollment.
• The health status is assessed by the investigator as "normal healthy" based on required screening assessments.
• Females of childbearing potential must have a negative human chorionic gonadotropin (hCG) test result within 28 days before enrollment and agree to use a highly effective method of contraception from enrollment up to the study end, such as:

• Intrauterine device
• Combined (estrogen- and progestogen-containing) hormonal contraception associated with the inhibition of ovulation (oral, intravaginal, or transdermal)
• Progestogen-only hormonal contraception associated with the inhibition of ovulation (oral, injectable, intrauterine, or implantable)
• Tubal ligation
• Vasectomized male partner
• Sexual abstinence

Female subject being postmenopausal for at least 1 year or surgically sterile is considered to be of no childbearing potential.

• Able and willing to comply with scheduled clinic visits and clinical trial procedures.
• Capable of understanding and giving signed informed consent form after full discussion of the research nature of the treatment and its risk and benefits with the investigator/ designee of the sponsor.

Exclusion criteria

• History of surgical treatment for the target superficial lipoma or submental area (Part II Kybella cohort only).
• Current infection or wound near the target superficial lipoma or the submental area (Part II Kybella cohort only).
• History of diabetes.
• Allergic to excipients of Ronkyla Plus or Kybella (Part II Kybella cohort only)
• A result on coagulation tests (prothrombin time, activated partial thromboplastin time) obtained within 28 days before enrollment that indicates the presence of any clinically significant bleeding disorder (subjects being treated with antiplatelet therapy or anticoagulants could be enrolled after 7-day washout period):

• Prothrombin time > 20 seconds.
• Activated partial thromboplastin time > 60 seconds.
• INR > 3.
• Any ongoing medical condition with significant risk of bleeding
• Evidence of any serious active infections, COVID 19, severe uncontrolled cardiac, renal, hepatic, pulmonary or other systemic disease, significant medical or psychiatric condition, known seropositivity to HIV/HBV/HCV, or clinically significant laboratory findings that would, in the investigator's judgment, make the subject inappropriate for the study.
• Administration of an investigational drug within 30 days prior to enrollment.
• Administration of a COVID-19 vaccine within 30 days prior to enrollment.
• Abnormal hepatic and renal functions; hematologic changes at screening:

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 X upper limit of normal (ULN).
• Total bilirubin > 1.5 X ULN.
• Serum creatinine > 1.5 X ULN.
• Hemoglobin < lower limit of normal (LLN).
• Platelets ≤ 100.000/mm³.
• Current malignancy of any organ system or a history within 5 years.
• Subjects who, in the opinion of the investigator, are not likely to complete the trial for whatever reason.

Part I & Part II Ronkyla Plus cohort specific exclusion criteria:

• History of any medical condition contraindicated or not recommended for aspirin use including active peptic ulcer disease, asthma, gout, uncontrolled hypertension.
• Taking any medication contraindicated or not recommended for concomitant use with aspirin within 7 days prior to enrollment.
• Allergic to Aspirin, salicylates, or non-steroidal anti-inflammatory drugs (NSAIDs).
• The target lipoma warrants surgical removal per the investigator's judgement (e.g., for confirming its pathology).

Part I dose level 2 and 4 cohorts & Part II specific exclusion criteria:

• History of alcohol or drug abuse within the past year prior to Day 1.
• History of smoking or use of nicotine-containing product within 6 months prior to Day 1.
• Donation or significant loss of blood (480 mL or more) within 60 days prior to Day 1.