Single-dose GB18 injections in healthy adults (dose-escalation)

A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Phase I Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of GB18 Following Single Subcutaneous Injection in Healthy Adult Participants

This trial will test single subcutaneous doses of GB18 versus placebo in healthy adults to see if the drug is safe, how it behaves in the body, how it affects the circulating protein GDF15, and whether it triggers immune responses.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: Kexing Biopharm Co., Ltd. (industry)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07237464 on ClinicalTrials.gov

What this trial studies

This is a first-in-human, randomized, double-blind, placebo-controlled dose-escalation trial in healthy adults. Thirty-six participants will be enrolled across five sequential cohorts receiving a single subcutaneous dose of GB18 (50, 100, 200, 400, or 600 mg) or placebo with a 3:1 randomization in each cohort. The study will collect safety, tolerability, pharmacokinetics, pharmacodynamics (including circulating GDF15), and immunogenicity data with inpatient dosing and multiple follow-up visits through roughly four months. Safety review committees will review tolerability before escalating doses.

Who should consider this trial

Good fit: Healthy men and women aged 18–55 with body weight and BMI within the study limits who can comply with CRU admission, follow-up visits, and contraception requirements are ideal candidates.

Not a fit: People with active cancer, cachexia, or other major health conditions should not expect direct therapeutic benefit from this healthy-volunteer first-in-human trial.

Why it matters

Potential benefit: If successful, the trial could identify a safe dose and pharmacologic profile to support further testing of GB18 as a potential treatment approach for cancer cachexia.

How similar studies have performed: Modulating GDF15 is an emerging approach supported by preclinical data, but GB18 itself is novel and this is its first-in-human test.

Eligibility criteria

Inclusion Criteria:

1. Participants who have signed the informed consent form (ICF) prior to the study, fully understand the content, procedures, and possible adverse reactions of the study, and are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
2. Male and female participants aged 18-55 years (inclusive), at the time of signing the ICF.
3. Body weight ≥ 50 kg for males and ≥ 45 kg for females, with a body mass index (BMI = weight (kg)/height 2 (m) 2) of 18.5-26 kg/m2 (inclusive).
4. Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, Vital signs, 12-lead ECG, and laboratory tests.
5. Participants (including their partners) who have no plan to become pregnant and voluntarily use effective contraception from screening to 6 months after the last dose.

Exclusion Criteria:

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
2. History of HIV infection, syphilis, hepatitis B, or hepatitis C; positive testing for HIV, syphilis, HBsAg, or HCVAb.
3. History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody or molecules made of components of monoclonal antibodies.
4. History of recurrent infections or active infections.
5. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior, or other conditions that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
6. Smoking more than five cigarettes per day on average, or habitually used nicotine containing products, or unable to refrain from smoking during the trial.
7. Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention.
8. Exposure to live vaccines within 28 days of screening.
9. Previous administration with an investigational drug within 30 days or marketed or investigational monoclonal antibodies within 3 months or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
10. History of drug abuse within the past 5 years or use of drugs in the 3 months prior to screening, or a positive urine drug test at screening.
11. Screening BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
12. Screening 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline QTcF interval \>450 msec, or QRS interval \>120 msec). If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values should be used to determine the participant's eligibility.
13. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary:

    * AST or ALT level ≥1.5 × ULN,
    * Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.
14. History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 3 months of Screening. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 360 mL beer, 45 mL of 40% spirit or 150 mL of wine).
15. Blood donation (excluding plasma donations) of approximately 400 mL or more within 60 days prior to dosing.
16. Participants who, in the judgment of the investigator, are not suitable for participation in the study.
17. Skin scar, rash, or ulceration at the injection site (abdomen).
18. History of vasovagal syncope or needle phobia, and inability to tolerate venous indwelling catheter blood collection.
19. Participants who plan to donate sperm or oocytes within 6 months after administration of the investigational drug.

Where this trial is running

Beijing, Beijing Municipality

• Beijing GoBroad Hospital — Beijing, Beijing Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Kangsheng Yang

Conditions: Cancer Cachexia, Cancer Cachexia Syndrome, Cancer cachexia, GB18, healthy adult, Phase I, pharmacokinetics, pharmacodynamics