Effect of anti-obesity agent HSG4112 on overweight and obese patients following 12 weeks of oral treatment: a study protocol for a randomised, double-blind, placebo-controlled, parallel-group, phase 2a clinical trial

Background: Glaceum Inc. has proposed HSG4112, a structural analogue of glabridin, as a novel anti-obesity compound. Animal studies and phase I human trials have shown that HSG4112 improves energy consumption, normalises weight, and is safe and drug-resistant. Based on these results, the company plans to conduct a phase 2a clinical trial to determine the safety and efficacy of HSG4112 in overweight and obese patients. Methods: A 16-week randomised, double-blind, placebo-controlled, parallel-group trial will be conducted at five large hospitals in South Korea to assess the safety and efficacy of HSG4112 in overweight and obese patients. Participants who meet the inclusion/exclusion criteria will be assigned a subject number and randomly assigned to one of the four treatment groups (one group receiving a placebo) in a 1:1:1:1 ratio. The study’s primary outcome will be to monitor the change in body weight (kg) from baseline to the end of treatment while monitoring safety and tolerability. Discussion: This trial will evaluate the efficacy and safety of HSG4112 in overweight and obese adults. Upon proving the safety and effectiveness of the newly developed mechanism, it might significantly improve the perception of the product among medical personnel and obese patients. Furthermore, it may aid in managing chronic conditions that require long-term treatment. Trial registration: ClinicalTrials.gov, identifier [NCT05197556].

3) The BMI should be between 30 and 39.9 kg/m 2 , inclusive (obese), with or without comorbid conditions.The BMI should be between 27 and 29.9 kg/m 2 , inclusive (overweight), with at least one documented treated or untreated comorbid condition (e.g., hypertension, dyslipidaemia, cardiovascular disease, glucose intolerance, and sleep apnoea).All comorbid conditions were considered clinically stable by the investigator.
-(BMI (kg/m 2 ) = weight (kg) / {height (m) 2 } 4) The following are the requirements for females: -Females of childbearing potential who are not pregnant, evidenced by a negative serum hCG pregnancy test at screening.
-Non-lactating, surgically sterile (defined as documented bilateral tubal ligation, bilateral tubal occlusion, bilateral oophorectomy, hysterectomy), or postmenopausal (defined as at least 12 months prior to screening without menses without an alternative explanation for the absence of menses).
5) Eligible males must not have planned to have children within 90 days after the last day of treatment.
6) At least one unsuccessful weight loss attempt, as determined by the investigator.

Study population -Exclusion Criteria
1) Clinically significant newly diagnosed illness, per investigator judgment, 1 month before screening and during the screening period.
2) Significant history or clinical evidence of allergic reactions or hypersensitivity to IP or any related drug compound.
3) Compliance with placebo self-administration was ≤80% during the initial 2-week single-blind placebo run-in period.

27)
Recent history (i.e., within two years prior to the screening visit) of alcohol or drug abuse or a positive drug test at screening.Participants with a positive drug screen may be eligible with approval from the sponsor.This is if the participant has a documented medical history requiring chronic pain treatment and a documented concomitant medication resulting in a positive drug screen.Additionally, the investigator considers the participant to be reliable for this study.
28) Significant changes in smoking habits within 3 months prior to screening, as determined by the investigator.
29) The participant has participated in any other clinical or bioequivalence study and has been dosed with an IP within 6 months before the first day of treatment.Unless documentation indicates that the participant received a placebo, the participant is ineligible.
30) Significant changes in diet or level of physical activity within 1 month prior to screening, based on the investigator's judgment.
31) Weight loss or gain of more than 5% within 3 months prior to the screening visit by history or documentation.
32) The participant is unwilling, or whose partner is unwilling, to use medically acceptable contraception during and for 90 days following completion or withdrawal of the study.
Medically acceptable contraceptive methods include the following: -Hormonal contraceptive -Intrauterine device that has been demonstrated to be effectively used by the participant or the participant's spouse/partner.
-Physical contraception (male or female) used with chemical sterilisation.
33) Participants who, in the opinion of the investigator, should not participate in this study based on clinical laboratory test results or other reasons.

Schedule of data collection -Detailed description
1) In cases of early termination of follow-up or discontinuation of the study, the followup visit was performed 4 weeks after the last IP administration.
2) The first and second procedures can be performed on the same day.However, the tests and procedures to be performed at the screening visit must be completed prior to the suitability evaluation and randomisation of the inclusion/exclusion criteria.
3) Randomisation: Eligible participants were stratified according to baseline BMI and randomised in a 1:1:1:1 ratio into four treatment groups on day 1.
4) Dispensation and restitution of IP/placebo: Participant compliance was evaluated based on the quantity of test drugs delivered to the participants and the number of test drugs returned.
5) Distribution Diet/Physical Activity Diaries: Between visits two and five, diaries were distributed to participants to record their food intake and physical activity per the instructions.
6) DEXA: The result on day 1 may be replaced if there is a measurement result between days 1 and 17.
7) BMI calculation: Height is determined during the first visit.
8) Anthropometrics: Measure the circumference of the waist and the waist-to-hip ratio.

12)
Drug abuse tests: Barbiturates, cocaine, opiates, and cannabinoids testing were performed.13) Serologic tests: HBsAg, HCV Ab, HIV Ag/Ab, and VDRL testing were performed.14) Pregnancy test: For women of childbearing potential, serum pregnancy tests will be conducted during screening and urine pregnancy tests from the third to the sixth visits.15) Reproductive hormone tests: Testosterone (total and free), LH, FSH, and SHBG tests were performed.16) Sampling for genetic research: Participants can participate in this study without participating in the exploratory genetic research part.Participants in exploratory genetic research must sign a consent form for the main study and a separate consent form for experimental genetic research.