Clinical trial NCT06859853: A Study to Evaluate MWN109 Injection in Healthy Subjects
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single-and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MWN109 Injection in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Overweight or Obese
Lead sponsor: Shanghai Minwei Biotechnology Co., Ltd
Sponsor class: INDUSTRY
First posted: 2025-03-05
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study is a Phase1, randomized, double-blinded, and placebo-controlled study. In each cohort, enrolled participants will be randomized to receive either placebo or MWN109.

Detailed description: A total of 72 healthy volunteers are expected to be enrolled into this study. Study consists of 2 parts- Part A- Single Ascending dose (SAD) and part B- Multiple ascending dose (MAD).

The entire study duration per participant is estimated to be a maximum of 8 weeks for the single ascending dose (SAD) part and 12 weeks for the multiple ascending dose (MAD) part. The end of study is defined as the date of the last visit of the last participant in the study.

Eligibility criteria: Inclusion Criteria:

1. Males or females, of any race, aged 18 to 50 years (inclusive) at Screening.
2. \[Part A: SAD\] BMI of 19.0 to 40.0 kg/m2 (inclusive). \[Part B: MAD\] BMI of 27.0 to 45.0 kg/m2 (inclusive) with a minimum body weight of 50.0 kg for females and 55.0 kg for males.
3. History of stable body weight for 3 months (defined as change \< 5%).
4. Resting heart rate (supine) ≥ 45 bpm and ≤ 90 bpm with a single 12-lead ECG at Screening.
5. Females of childbearing potential and males will agree to use contraception as detailed further in the protocol.
6. Male participants must agree to refrain from sperm donation and females should refrain from ova donation from D-1 until 4 months after the last administration.
7. Able to comprehend and willing to sign an ICF and to abide by all study requirements and restrictions.

Exclusion Criteria:

1. Significant history or clinical manifestation of any cardiovascular, metabolic, allergic, endocrine, renal, hepatic, gastrointestinal, hematological, pulmonary, respiratory, dermatological, neurological, gynecological, psychiatric, disorders as determined by the investigator (or designee).
2. History of pheochromocytoma or has uncontrolled blood pressure, as defined as systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg.
3. History of insulinoma or has an event of blood glucose \< 2.8 mmol/L within 1 year prior to Screening, or with ≥ 3 times of hypoglycemia symptoms within 3 months prior to Screening.
4. History of febrile illness within 7 days prior to the first dose of IP or participants with evidence of active infection.
5. Any of the following:

   1. QTcF \> 450 msec regardless of gender , confirmed by repeat measurement.
   2. QRS duration \> 110 msec confirmed by repeat measurement.
   3. PR interval \> 220 msec confirmed by repeat measurement.
   4. Findings which would make QTc measurements difficult or QTc data uninterpretable.
   5. History of additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome).
6. Known history or family history of thyroid C-cell tumor/carcinoma, multiple endocrine neoplasia syndrome type 2 (MEN2), thyroid dysfunction or thyroid hormone abnormality.
7. History of diabetes mellitus Type I or II or clinical evidence of diabetes (e.g., hemoglobin A1c ≥ 6.5%, fasting blood glucose ≥ 126 mg/dL \[7.0 mmol/L\]) at Screening, non-fasting glucose ≥ 200 mg/dL (11.1 mmol/L) at Screening, or use of any hypoglycemic drugs during Screening or within 3 months prior to Screening
8. History of acute or chronic pancreatitis, symptomatic gallbladder disease, pancreatic injury and other high-risk factors that may lead to pancreatitis.
9. With any of following laboratory abnormality:

   1. Elevation in serum amylase or lipase (\> 1.5 × upper limit of normal \[ULN\]).
   2. Have serum AST or ALT \> 2 × ULN or total bilirubin \>1.5 × ULN.
   3. Have serum TG ≥ 5.65 mmol/L (500 mg/dL) at screening
   4. Estimated glomerular filtration rate (eGFR) \< 90 mL/min/1.73m2.
10. History of clinically significant abnormal gastric emptying (e.g., gastric outlet obstruction, gastroparesis), severe chronic gastrointestinal diseases (e.g., having active ulcer within 6 months prior to Screening, active gastritis or esophagitis, or uncontrolled gastroesophageal reflux disease, irritable bowel disease or severe inflammatory bowel disease).
11. Long-term use of drugs directly affecting the gastrointestinal motility (including but not limited to mosapride, cisapride) or gastrointestinal surgery within 12 weeks prior to Screening and are inappropriate for participation in this clinical study as assessed by the Investigator.
12. Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), or human immunodeficiency virus (HIV-1 and HIV-2) antibodies and p24 antigen.
13. Any history of severe psychiatric disorder such as major depressive disorder, bipolar disorder, and schizophrenia, or history of suicidal ideation, behavior or attempts or other psychiatric disorder (within 2 years of Screening).
14. Any suicidal ideation as identified by endorsement of (answered yes to) any of the items numbered 1-5 on the Columbia Suicide Severity Rating Scale (C-SSRS), if applicable.
15. History of alcoholism or drug/chemical abuse within 1 year prior to D-1.
16. Alcohol consumption of \> 21 units per week for males and \> 14 units per week for females, on average. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.
17. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) during the Screening period.
18. Daily use of more than 10 cigarettes/day (on average), or 2 cigars/day (on average), or equivalent use of any tobacco product within 6 weeks prior to Screening.
19. Females of pregnant or lactating, or those with a positive pregnancy test at Screening.
20. Intolerance to venipuncture for blood sampling or history of fainting at blood drawing or sight of blood, unless deemed acceptable by the Investigator (or designee).
21. History of severe Types I-IV hypersensitivity reactions, anaphylaxis, cytokine release syndrome, atopic individuals, or allergic reactions to multiple drugs. If the Investigator is considering enrolling a participant with drug allergies, agreement with the Medical Monitor should be sought.
22. History of or suspected allergy or hypersensitivity to the investigational product or its components
23. Use or intend to use any prescription medications/products other than hormone replacement therapy, oral, implantable, transdermal, injectable, or intrauterine contraceptives within 14 days prior to dosing, unless deemed acceptable by the Investigator (or designee).
24. Use or intend to use slow-release medications/products considered to still be active within 14 days prior to D-1, unless deemed acceptable by the Investigator (or designee).
25. Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 7 days prior to D-1, unless deemed acceptable by the Investigator (or designee).
26. Participants with a history of infectious diseases (which may affect the ability of the participant to participate in the study at the discretion of the Investigator), severe trauma, or major surgical operation within 4 weeks prior to Screening.
27. Have been vaccinated within 4 weeks prior to Screening or plan to have vaccination during the study.
28. Donation of blood or massive blood loss (\> 450 mL) OR receipt of blood products within 12 weeks prior to Screening.
29. Participation in a clinical study involving administration of an investigational agent/device or vaccine (new chemical entity) or having received a biological product within 12 weeks prior to Screening.
30. Poor peripheral venous access.
31. Are investigative site personnel directly affiliated with this study and their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
32. The presence of clinically significant physical examination, vital sign, drug, or ECG findings at Screening or baseline or laboratory findings at Screening that, in the opinion of the Investigator or Medical Monitor, may interfere with any aspect of study conduct or interpretation of results.
33. Any skin condition and/or tattoo that may interfere with the evaluation of safety at the injection site.
34. Are deemed unsuitable by the Investigator (or designee) for any other reason.

Primary outcomes:
measure: Number of participants with Incidence of treatment emergent adverse events (TEAEs) following treatment administration
timeFrame: Part A- Up to Day 29; Part B- Up to Day 50 post first dose administration
measure: Number of participants with change in laboratory parameters following treatment administration
timeFrame: Part A- Up to Day 29; Part B- Up to Day 50 post first dose administration
measure: Number of participants with change in Vital signs following treatment administration
timeFrame: Part A- Up to Day 29; Part B- Up to Day 50 post first dose administration
measure: Incidence of anti-drug antibody (ADA) formation following treatment administration
timeFrame: Part A- Up to Day 29; Part B- Up to Day 50 post first dose administration
Secondary outcomes:
measure: PK parameters- Cmax: maximum observed concentration
timeFrame: SAD- Up to Day 29; MAD- Up to Day 50 post first dose administration.
measure: PK parameters- -Tmax: time to reach maximum concentration
timeFrame: SAD- Up to Day 29; MAD- Up to Day 50 post first dose administration.
measure: PK parameters- t½: half-life
timeFrame: SAD- Up to Day 29; MAD- Up to Day 50 post first dose administration.
measure: PK parameters- AUC0-inf: area under the concentration-time curve from time zero to the theoretical infinite time
timeFrame: SAD- Up to Day 29; MAD- Up to Day 50 post first dose administration.
measure: PK parameters- AUCo-t: area under the concentration-time curve from time zero to the time of the last quantifiable concentration
timeFrame: SAD- Up to Day 29; MAD- Up to Day 50 post first dose administration.
measure: PK parameters- AUC0-168h: area under the concentration-time curve from time zero to 168 h post dose
timeFrame: SAD- Up to Day 29; MAD- Up to Day 50 post first dose administration.
measure: PK parameters- CL/F: apparent clearance
timeFrame: SAD- Up to Day 29; MAD- Up to Day 50 post first dose administration.
measure: PK parameters- Vd/F: apparent volume of distribution
timeFrame: SAD- Up to Day 29; MAD- Up to Day 50 post first dose administration.
measure: PK parameters- MRT: mean residence time
timeFrame: SAD- Up to Day 29; MAD- Up to Day 50 post first dose administration.
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Veritus Research
state: Victoria
Study officials:
affiliation: Shanghai Minwei Biotechnology
name: Guitao Zhang
role: STUDY_CHAIR
References: