First-in-Human Study of ISH0688: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics

NCT07505043 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: ISH0688-101
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

ISH0688 is a human IgG1 Fc-FGF21 fusion protein. The objectives of the planned clinical investigation will be to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single- and multiple-ascending doses of ISH0688 via subcutaneous injection.

Conditions

Healthy Subjects; Hyperlipidemia, Hypertriglyceridemia

Outcome Measures

Primary Outcomes (2)

• Number of participants with treatment-emergent adverse events [Safety and Tolerability]

  Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0

  baseline through day 99 (part 1) or day 84 (part 2)

• Injection site reactions assessments

  The injection site reaction assessment will be done by the PI/investigational staff and study subject using the criteria, which consist of rating the severity of redness, swelling, skin temperature, sensitivity and pain at the injection site

  baseline through day 99 (part 1) or day 84 (part 2)

Secondary Outcomes (52)

• Maximum observed serum concentration (Cmax)

  baseline through day 99 (part 1) or day 84 (part 2)

• Time to reach maximum observed serum concentration (Tmax)

  baseline through day 99 (part 1) or day 84 (part 2)

• AUC from time 0 to the time of the dosing interval (AUC0-t)

  baseline through day 99 (part 1) or day 84 (part 2)

• AUC from time 0 to infinity (AUC₀-∞)

  baseline through day 99 (part 1) or day 84 (part 2)

• Terminal elimination half-life (t1/2)

  baseline through day 99 (part 1) or day 84 (part 2)

Study Arms (4)

Single-ascending dose：Part1：ISH0688

EXPERIMENTAL

Drug: ISH0688 for injection

Single-ascending dose：Part1：placebo

PLACEBO COMPARATOR

Drug: Placebo

Multiple-ascending dose：Part2：ISH0688

EXPERIMENTAL

Drug: ISH0688 for injection

Multiple-ascending dose：Part2：placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

ISH0688 for injection DRUG

75、150、300、600 mg; s.c. Q4W; Sterile powder for injection

Multiple-ascending dose：Part2：ISH0688; Single-ascending dose：Part1：ISH0688

Placebo DRUG

75、150、300、600 mg; s.c. Q4W; Sterile powder for injection

Multiple-ascending dose：Part2：placebo; Single-ascending dose：Part1：placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female subjects:
• Not of childbearing potential: Including surgical sterilization performed at least 6 weeks prior to screening (with documented records of bilateral tubal ligation, bilateral salpingectomy, hysterectomy, or bilateral oophorectomy), or postmenopausal with continuous amenorrhea for ≥12 months; or
• Of childbearing potential: Must not be pregnant or breastfeeding, and must agree to use adequate contraception from 30 days prior to first dosing throughout the study period and for 6 months after the last dose;
• Serum β-human chorionic gonadotropin (β-hCG) pregnancy test results must be negative at both screening and baseline visits;
• Male subjects with female partners of childbearing potential must agree to use adequate contraception from 30 days prior to first dosing throughout the study period and for 6 months after the last dose;
• Male subjects must have no plan to donate sperm from the time of informed consent signing until 6 months after study completion; female subjects must have no plan to donate eggs from the time of informed consent signing until 6 months after study completion;
• All subjects must be able to understand the procedures and methods of this study, be willing to strictly comply with the clinical study protocol to complete this study, and voluntarily sign the informed consent form.
• Male or female subjects aged 18 to 65 years (inclusive);
• Male body weight ≥50.0 kg, female body weight ≥45.0 kg, with body mass index (BMI) ≥19.0 and \<28.0 kg/m²;
• Fasting triglycerides (TG) \<2.3 mmol/L (200 mg/dL);
• Comprehensive vital signs, physical examination, 12-lead electrocardiogram (ECG), chest X-ray, abdominal ultrasound, and laboratory tests (complete blood count, blood biochemistry, urinalysis, stool routine, coagulation function, thyroid function) showing no abnormalities or only minor abnormalities that are judged by the investigator to be of no clinical significance. For clinically significant abnormal laboratory findings, retesting may be performed within one week if there is a clear and reasonable justification, and the retest results will be used to determine subject eligibility.
• Male or female subjects aged 18 to 75 years (inclusive);
• Male body weight ≥50.0 kg, female body weight ≥45.0 kg, with body mass index (BMI) in the range of 19.0 to 45.0 kg/m² (inclusive);
• Lipid levels at screening or within 1 week prior to screening (at this site) meeting: fasting TG ≥2.3 mmol/L (200 mg/dL);
• Lipid-lowering medication use within 28 days prior to screening must meet the following criteria: For TG \<5.7 mmol/L (500 mg/dL): no lipid-lowering medication use or receiving stable-dose lipid-lowering therapy for ≥28 days; For TG ≥5.7 mmol/L (500 mg/dL): must first receive stable-dose lipid-lowering therapy for ≥28 days; (Lipid-lowering therapy: niacin, prescription-grade fish oil, fibrates, statins, cholesterol absorption inhibitors, etc.; PCSK9 inhibitors require 6 months of stability prior to screening);

You may not qualify if:

• Undergo therapeutic lifestyle intervention during the lead-in period, maintain a stable lifestyle, and be judged by the investigator as capable of complying with the protocol to receive study treatment and complete other clinical trial procedures;
• Two TG tests during the lead-in period with an interval of ≥7 days, with the mean of the 2 TG values meeting 2.3 mmol/L (200 mg/dL) ≤ fasting TG \< 11.3 mmol/L (1000 mg/dL);
• The last TG test is within 7 days prior to the first dosing (D1).
• Subjects with current allergic diseases, history of allergy to therapeutic or diagnostic protein products, or allergy to two or more drugs and/or non-drug factors;
• Subjects with history of malignant tumors (regardless of cure status, except for basal cell carcinoma, squamous cell skin cancer, and cervical carcinoma in situ);
• Subjects with positive results for one or more of the following: hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab), or serum treponema pallidum antibody (TP-Ab) (if HBsAg positive, must also have positive HBV-DNA; if HCV-Ab positive, must also have positive HCV-RNA);
• Subjects with severe trauma or surgical history within 6 months prior to screening; or subjects planning to undergo surgery (including cosmetic surgery, dental surgery, and oral surgery, etc.) during the trial period;
• Subjects with body weight change ≥5% within 3 months prior to screening (self-reported), or use of other medications/treatments for weight reduction within 1 month prior to screening or planned during the study period;
• Subjects with history of frequent orthostatic hypotension episodes within 6 months prior to screening;
• Subjects with history of chronic pancreatitis or acute pancreatitis attack within 1 year prior to screening;
• Subjects with gallbladder history and symptoms (such as: common bile duct stones, multiple gallbladder stones, etc., unless cholecystectomy performed and ≥6 months since surgery);
• Subjects with alcohol consumption \>14 units per week within 3 months prior to screening (1 unit of alcohol = 360 mL beer, 150 mL wine, or 45 mL spirits with 40% alcohol content), or positive alcohol breath test (at baseline);
• Drug abusers or subjects using soft drugs (e.g., marijuana) within 3 months prior to screening or hard drugs (e.g., cocaine, phencyclidine, etc.) within 1 year prior to screening, or positive drug abuse screening (morphine, ketamine, tetrahydrocannabinol acid, methamphetamine, methylenedioxymethamphetamine, cocaine);
• Subjects who have used products targeting FGF21 within 1 year prior to screening, such as BIO89-100, DR10624, etc.;
• Subjects with history of vaccination within 3 months prior to screening, or planning to receive vaccination during the trial period;

Sponsors & Collaborators

• SUNHO（China）BioPharmaceutical CO., Ltd.: lead

Study Sites (1)

The First Affiliated Hospital of Henan University of Science and Technology

Luoyang, Henan, 471000, China

Location

MeSH Terms

Conditions

Hyperlipidemias; Hypertriglyceridemia

Interventions

Injections

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

Ya Ze Jiao

CONTACT

15950520087; 15950520087@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2026
• First Posted: April 1, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027
• Last Updated: April 1, 2026

Record last verified: 2026-03

Locations

CN (1)