Clinical trial NCT07009171: Study to Evaluate the Efficacy and Safety of KDS2010 in Overweight or Obese Patients
Official title: A Randomized, Double-blind, Placebo-controlled, Dose Finding, Phase 2a Clinical Trial to Evaluate the Efficacy and Safety of KDS2010 in Overweight or Obese Patients
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Overweight
Obesity
Obese Patients
Keywords: Obese Patients
Overweight
KDS2010
Obesity
MAO-B inhibitor
Lead sponsor: NeuroBiogen Co., Ltd
Sponsor class: INDUSTRY
First posted: 2025-06-06
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Phase 2a Clinical Trial
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, placebo-controlled, dose-escalation, Phase 2a study designed to evaluate the safety and efficacy of KDS2010 in overweight or obese patients. Based on preliminary efficacy observed in the Phase 1 study, a multinational clinical trial is being conducted in both Korea and the United States. After a minimum 2-week run-in period, subjects who meet the inclusion and exclusion criteria will be randomized into each dose group at a 2:1 ratio in Stage 1 and in a 1:1:1 ratio in Stage 2, considering stratification by region (Korea/USA).

Subjects will receive the investigational drug for 12 weeks following randomization. Approximately 75 subjects will be enrolled, with 6 subjects in the treatment group and 3 subjects in the control group in Stage 1, and 22 subjects per group in Stage 2.

The primary objectives are to assess the efficacy and safety of KDS2010 in overweight or obese patients. Exploratory objectives include evaluating the proportion of subjects achieving a weight reduction of more than 25% from baseline at Week 12 and assessing changes in MAO-B specific activity and adiponectin levels.

Based on nonclinical and Phase 1 clinical data, KDS2010 will be administered orally once daily at doses of 120 mg and 180 mg throughout the study.

Detailed description: This Phase 2a, multinational, randomized, double-blind, placebo-controlled, dose-finding clinical trial is designed to evaluate the efficacy, safety, and pharmacokinetics of KDS2010, a novel, reversible monoamine oxidase-B (MAO-B) inhibitor, in overweight or obese adult patients. The clinical trial is conducted at selected sites in Korea and the United States.

The study consists of two stages and will enroll approximately 75 subjects. In Stage 1, 9 subjects will be randomized in a 2:1 ratio (KDS2010 120 mg: placebo) to evaluate initial safety and tolerability. Upon completion of the week 13 visit for the last subject in Stage 1, a Safety Review Committee (SRC) will assess cumulative safety data to determine the appropriateness of dose escalation and progression to Stage 2.

If cleared by the SRC, Stage 2 will proceed with 66 subjects randomized equally across three arms in a 1:1:1 ratio: KDS2010 120 mg, KDS2010 180 mg, and placebo. Randomization will consider stratification by region (Korea/USA). All subjects will undergo a 2-week run-in period prior to randomization to confirm eligibility based on adherence to lifestyle modification (documented reduction of ≥500 kcal/day and ≥150 minutes of physical activity per week for ≥50% of the run-in period).

The treatment period consists of 12 weeks of once-daily oral administration of the investigational product (IP), followed by a 1-week post-treatment safety follow-up (week 13). During treatment, subjects will visit the site at Weeks 4, 8, and 12, with a telephone visit at Week 2. Safety follow-up will be conducted by phone at Week 13.

The primary efficacy endpoint is the percentage change in body weight from baseline to Week 12. Secondary efficacy endpoints include the proportion of subjects achieving ≥5%, ≥10%, ≥15%, and ≥20% weight loss and changes in waist circumference, BMI, blood pressure (SBP/DBP), quality of life (IWQOL-Lite-CT), body composition (DEXA), lipid profile, glycemic parameters (HbA1c, fasting glucose, HOMA-IR), and liver steatosis. Exploratory endpoints assess the proportion of subjects with ≥25% weight loss, as well as changes in MAO-B specific activity and adiponectin levels.

Safety will be evaluated through monitoring of adverse events (AEs), laboratory tests, vital signs, ECGs, and psychological assessments, including the Columbia-Suicide Severity Rating Scale (C-SSRS) and Patient Health Questionnaire-9 (PHQ-9). Pharmacokinetic parameters (AUCtau, Cmax,ss, Cmin,ss, Cav,ss, Tmax,ss, t1/2, PTF, etc.) will be measured to assess systemic exposure to KDS2010.

Subjects must be adults (≥18 years), have a BMI ≥30 kg/m² or ≥27 kg/m² with at least one weight-related comorbidity, and demonstrate compliance with lifestyle modification during the run-in. Major exclusion criteria include recent significant weight change (≥5% within 12 weeks), use of anti-obesity drugs or MAO inhibitors, type 1 or 2 diabetes, bariatric surgery, uncontrolled hypertension, hepatic or renal dysfunction, significant psychiatric disorders, or suicidal ideation/attempts.

The total study duration is expected to be approximately 24 months from the IRB/IEC approval, with individual subject participation lasting up to 17 weeks. This trial aims to evaluate the safety, efficacy, and pharmacokinetic of KDS2010 for future development in the treatment of obesity.

Eligibility criteria: Inclusion Criteria:

* Adult males and females aged 18 years or older (or the legal age of adulthood in the respective country) as of the date of written consent
* Subjects with BMI ≥30 kg/m² or BMI ≥27 kg/m² with at least one weight-related comorbidity (hypertension, dyslipidemia, cardiovascular disease, obstructive sleep apnea) at screening and baseline

  * Hypertension: under treatment or have Systolic Blood Pressure (SBP) ≥130 mmHg or Diastolic Blood Pressure (DBP) ≥80 mmHg
  * Dyslipidemia: under treatment or LDL \> 160 mg/dL or TG \> 200 mg/dL or HDL \< 40 mg/dL
  * Cardiovascular diseases (e.g., ischemic cardiovascular disease, NYHA Class I to III heart failure, Peripheral vascular disease (PVD), Abdominal aortic aneurysm (AAA), etc.)
  * Obstructive sleep apnoea
* Subjects who have documented a 500 kcal reduction/day in calorie intake and ≥150 minutes of physical activity/week for ≥50% of the time during the run-in period
* Subjects who have voluntarily provided written consent to participate after being informed about this clinical trial

Exclusion Criteria:

* Subjects with a weight change of 5% or more within 12 weeks before screening
* Subjects with less than 80% or more than 120% compliance during the Run-in period
* Subjects with obesity due to secondary causes (neurological disorders, endocrine disorders, genetic disorders, congenital disorders, etc.)
* Subjects with following medical history,

  * Type 1 or Type 2 diabetes
  * History of bariatric/metabolic surgery (e.g., adjustable gastric banding, intragastric balloon insertion, sleeve gastrectomy, Roux-en-Y gastric bypass, biliopancreatic diversion, duodenal switch) or planning to undergo such surgery during the study period
  * Heart failure classified as NYHA class IV
  * Subjects with a medical history of malignant tumors within 5 years prior to screening (however, subjects with successfully treated basal cell carcinoma, squamous cell carcinoma of the skin, thyroid cancer, or other carcinoma in situ, with no recurrence for more than 3 years, may be enrolled at the investigator's discretion)
  * Subjects with a medical history of hypersensitivity to MAO inhibitors
  * Subjects with a medical history of cerebrovascular disease (e.g., transient ischemic attack, stroke) within 12 weeks prior to baseline, or those hospitalized for unstable angina or congestive heart failure
  * Subjects with a history of depressive disorders or psychiatric disorders (e.g., schizophrenia, bipolar disorder, anxiety disorder) within 2 years prior to screening
* Subjects with a history of the following drug administration,

  -- Anti-obesity agents or weight-loss medications (including dietary supplements and herbal medicine) within 12 weeks before screening
  * Corticosteroids administered for 2 consecutive weeks or more within 12 weeks before screening (however, topical preparations, including inhalants, are allowed)
  * Treatment for hyperthyroidism or hypothyroidism at the time of screening (subjects on a stable dose and regimen for at least 12 weeks may be enrolled at the investigator's discretion)
  * MAO inhibitors within 2 weeks before baseline
  * Opioid medications (e.g., pethidine, Tramadol, Tapentadol) within 2 weeks before baseline
  * Serotonergic drugs within 2 weeks before baseline,

    * Selective Serotonin Reuptake Inhibitors (SSRI), ② Serotonin-Norepinephrine Reuptake Inhibitors (SNRI),

      * Tricyclic or Tetracyclic antidepressant, ④ Triazolopyridine antidepressant, ⑤ Selective serotonin (5-HT1) agonists (Sumatriptan, etc.), (However, amitriptyline ≤50 mg/day, trazodone ≤100 mg/day, citalopram ≤20 mg/day, sertraline ≤100 mg/day, paroxetine ≤30 mg/day are allowed; long half-life serotonergic drugs (e.g., fluoxetine) require at least a 5-week wash out period before enrollment),
  * Lithium, Bupropion, Lamotrigine, Ritonavir, Cyclobenzaprine, or St. John's wort within 2 weeks before baseline
  * Hypertension crisis-inducing drugs (e.g., oxymetazoline, phentermine, phenylephrine) within 2 weeks before baseline
  * Sympathomimetic agents (e.g., ephedrine, methylphenidate, amphetamine, methamphetamine, lisdexamfetamine) at the time of screening
  * Dextromethorphan at the time of screening
* Subjects who meet following criteria based on the tests conducted at Screening

  * Glycated hemoglobin (HbA1c) ≥6.5%
  * Hepatic impairment (Child-pugh class C)
  * AST or ALT \> 2.5 X ULN
  * Total bilirubin \>1.5 X ULN (however, \>3.0 mg/dL is acceptable in cases of Gilbert syndrome)
  * Severe renal impairment (eGFR \<30 mL/min/1.73 m² calculated using the MDRD formula\*),

    \* eGFR = 175 X (Serum creatinine)-1.154 X (Age)-0.203 X (0.742 (for females)) X (1.212 (for African Americans))
  * TSH \>6.0 mIU/L or \<0.4 mIU/L,
* Subjects with a lifetime history of suicide attempts
* Subjects with a PHQ-9 score of 10 or higher at screening
* Subjects who answer affirmatively to item 4 or 5 on the C-SSRS at screening
* Pregnant or breastfeeding women
* Females of childbearing potential and males who do not agree to use adequate contraception# until at least 2 weeks after the last dose of the IP or who plan to conceive during the study period,

  * Adequate contraception is defined as double contraception using both barrier methods (male condom or female condom) and one of the contraceptive methods ①-③.

    * Hormonal contraceptive (oral, injectable, implantable, etc.), ② Implantation of Intrauterine device (IUD) or intrauterine system (IUS), ③ Sterilization procedures or surgeries (bilateral tubal ligation, hysterectomy, vasectomy), ④ Complete abstinence: absolute abstinence is accepted if, in the investigator's judgment, the subject's age, occupation, lifestyle, or sexual orientation ensure compliance with contraception. However, periodic abstinence (calendar method, ovulation method, symptothermal method, etc.) withdrawal, and coitus interruptus are not considered adequate contraceptive methods.,
* Subjects who have participated in another clinical trial and received an investigational drug or device within 4 weeks prior to screening
* Other reasons (such as a medical history of alcohol or substance abuse) that the investigator deems the subject unsuitable for participation in this clinical trial

Primary outcomes:
measure: Percentage Change in Body Weight from Baseline
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Proportion of Subjects with ≥5%, ≥10%, ≥15%, and ≥20% weight loss from baseline (%)
timeFrame: Baseline to Week 12
measure: Change from baseline in Waist Circumference
timeFrame: Screening(Week -4 to -2), Run-in(Week -2), Baseline(Week 0), Week 4, 8, 12
measure: Change from baseline in Body Mass Index (BMI)
timeFrame: Screening(Week -4 to -2), Run-in(Week -2), Baseline(Week 0), Week 4, 8, 12
measure: Change from baseline in Systolic and Diastolic Blood Pressure
timeFrame: Screening(Week -4 to -2), Run-in(Week -2), Baseline(Week 0), Week 4, 8, 12, 13
measure: Change from baseline in Impact of Weight on Quality of Life Questionnaire-Lite Clinical Trials version (IWQOL-Lite-CT) Total and Domain Scores
timeFrame: Baseline(Week 0), Week 12
measure: Change from baseline in Body Fat Composition via Dual-energy X-ray absorptiometry (DEXA) Scan
timeFrame: Baseline(Week 0), Week 12
measure: Change from baseline in Lipid Profile
timeFrame: Screening(Week -4 to -2), Baseline(Week 0), Week 4, 8, 12, 13
measure: Change from baseline in Glycemic Parameters: HbA1c (%) and Fasting Glucose (mg/dL)
timeFrame: Screening(Week -4 to -2), Baseline(Week 0), Week 4, 8, 12, 13
measure: Change from baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
timeFrame: Baseline(Week 0), Week 12
measure: Change from baseline in Liver Steatosis (Abdominal CT)
timeFrame: Baseline(Week 0), Week 12
Other outcomes:
measure: Number of subjects with treatment-related Adverse Events (AEs)
timeFrame: Conducted from screening (Week -4 to -2) through Treatment (Week 0 to 12) and Follow-up (Week 13)
measure: Change from baseline in laboratory test results
timeFrame: Screening(Week -4 to -2), Baseline(Week 0), Week 4, 8, 12, 13
measure: Change from baseline in pulse rate
timeFrame: Screening(Week -4 to -2), Run-in(Week -2), Baseline(Week 0), Week 4, 8, 12, 13
measure: Change from baseline in body temperature
timeFrame: Screening(Week -4 to -2), Run-in(Week -2), Baseline(Week 0), Week 4, 8, 12, 13
measure: Change from baseline in Electrocardiogram(ECG)
timeFrame: Screening(Week -4 to -2), Week 12, 13
measure: Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) total score
timeFrame: Screening(Week -4 to -2), Baseline(Week 0), Week 4, 8, 12
measure: Change from baseline in Patient Health Questionnaire-9 (PHQ-9)
timeFrame: Screening(Week -4 to -2), Baseline(Week 0), Week 4, 8, 12
measure: Proportion of Subjects with ≥25% Weight Loss at Week 12
timeFrame: Baseline to Week 12
measure: Percentage Change in Monoamine Oxidase B (MAO-B) Specific Activity
timeFrame: Baseline(Week 0), Week 12
measure: Percentage Change in Adiponectin Levels
timeFrame: Screening(Week -4 to -2), Baseline(Week 0), Week 4, 8, 12, 13
measure: Pharmacokinetic Parameters: Area Under the Plasma Concentration-Time Curve over the dosing interval (τ) (AUCtau) at steady-state
timeFrame: Baseline(Week 0), Week 4, 8, 12
measure: Pharmacokinetic Parameters: Peak Plasma Concentration at Steady State (Cmax,ss)
timeFrame: Baseline(Week 0), Week 4, 8, 12
measure: Pharmacokinetic Parameters: Minimum Plasma Concentration at Steady State (Cmin,ss)
timeFrame: Baseline(Week 0), Week 4, 8, 12
measure: Pharmacokinetic Parameters: Average Plasma Concentration at Steady State (Cav,ss)
timeFrame: Baseline(Week 0), Week 4, 8, 12
measure: Pharmacokinetic Parameters: Time to Maximum Plasma Concentration at Steady State (Tmax,ss)
timeFrame: Baseline(Week 0), Week 4, 8, 12
measure: Pharmacokinetic Parameters: Terminal Elimination Half-life (t1/2)
timeFrame: Baseline(Week 0), Week 4, 8, 12
measure: Pharmacokinetic Parameters: Peak-Trough Fluctuation at Steady State (PTF)
timeFrame: Baseline(Week 0), Week 4, 8, 12
Locations:
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent's Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital
Study officials:
affiliation: NeuroBiogen Co., Ltd
name: Sangwook Kim, Chief Executive Officer
role: STUDY_DIRECTOR
References: