Phase I Trial of Subcutaneous VDJ010 In Healthy Subjects and Patients With Ulcerative Colitis

Inclusion Criteria:

• Healthy Subjects:

  1. Signed informed consent form and able to comply with the study protocol.
  2. Age ≥ 18 and ≤ 55 years (on the date of signing ICF); body weight ≥ 45.0 kg for women and ≥ 50.0 kg for men; BMI 18.0-28.0 kg/m² (inclusive).
  3. Normal function of major organs (heart, lung, liver, kidney).
  4. Negative serum pregnancy test for women of childbearing potential; willingness to use adequate contraceptive methods (e.g., abstinence, IUD, condoms) during the study and for 6 months after dosing.

• UC Patients:

  1. Age ≥ 18 and ≤ 75 years (on the date of signing ICF); male and female.
  2. Confirmed diagnosis of ulcerative colitis for ≥ 3 months prior to screening, per Chinese UC Diagnostic and Treatment Guidelines (2023, Xi'an), confirmed by endoscopy and histology within 14 days prior to randomization.
  3. Active UC defined as modified Mayo score ≥ 4 and ≤ 9, with stool frequency subscore ≥ 1, rectal bleeding subscore ≥ 1, and endoscopic subscore ≥ 2 (colonoscopy within 14 days acceptable).
  4. If UC history > 10 years, documented colonoscopy within 12 months prior to screening (or at screening). Those with family history of CRC, age > 50, or high-risk factors per investigator must have up-to-date CRC screening results.
  5. Negative serum pregnancy test for women of childbearing potential; male and female participants with reproductive potential must agree to use acceptable contraception during treatment and for 6 months after last dose.
  6. UC inflammation confirmed to extend proximal to the rectum, beyond the rectosigmoid junction (≥ 15 cm from anal verge) by colonoscopy.
  7. Voluntary participation with signed ICF.
  8. For patients on baseline UC therapies, the following washout/stability requirements must be met prior to randomization:

Oral 5-ASA agents: stable dose ≥ 2 weeks; Oral corticosteroids (prednisolone ≤ 25 mg/day or equivalent): stable dose ≥ 2 weeks Oral budesonide (≤ 9 mg/day): stable dose ≥ 2 weeks; Oral immunomodulators (MTX, AZA, 6-MP): stable dose ≥ 12 weeks

Exclusion Criteria:

• Healthy Subjects:

  1. Allergic constitution (allergy to two or more drugs/foods).
  2. History of malignancy, neurological or psychiatric disorders (including epilepsy or dementia), heart failure, immunodeficiency, immunosuppressive disease, or IBD; or major surgery within 6 months prior to randomization.
  3. Severe bleeding tendency affecting venous access, or unable/unwilling to undergo venipuncture.
  4. Vaccination within 1 month prior to randomization.
  5. Prior treatment with anti-IL-2 or IL-2 receptor-targeted therapy; use of any biologic agent within 6 months prior to randomization or currently.
  6. Participation in another clinical trial with drug administration within 3 months prior to randomization.
  7. Blood donation (whole blood or components) or significant blood loss (≥ 400 mL) within 3 months prior to randomization.
  8. Active bacterial, viral, fungal, or parasitic infection, or any infection requiring systemic anti-infective therapy within 4 weeks prior to randomization.
  9. Use of any medication (e.g., warfarin, cyclosporine, theophylline, simvastatin, omeprazole, dextromethorphan, Chinese patent medicine) or health supplements (vitamins, dietary supplements) within 2 weeks, or prescription medication within 1 month prior to randomization.
  10. History of drug abuse within 1 year or positive urine drug screen.
  11. Alcoholism or regular alcohol consumption > 14 units/week within 3 months (1 unit = 360 mL beer or 45 mL 40% spirit or 150 mL wine); positive alcohol breath test.
  12. Average daily smoking > 5 cigarettes within 3 months prior to first dose, or unable to abstain from tobacco during the study.
  13. Excessive daily consumption of tea, coffee, or caffeinated beverages (> 8 cups/day, 1 cup = 250 mL).
  14. Clinically significant abnormal findings on comprehensive physical examination, including: abnormal vital signs; clinically significant abnormal lab tests (hematology, urinalysis, liver function, renal function, coagulation), with mandatory exclusions for ANC ≤ 1.5×10⁹/L, platelet count ≤ 100×10⁹/L, AST or ALT > 2×ULN; clinically significant ECG abnormalities, PR ≥ 210 ms, QRS ≥ 120 ms, QTcF ≥ 450 ms.
  15. Positive T-SPOT.TB (may accept up to 2-fold ULN if no TB history and no symptoms).
  16. Positive for HIV-Ab, TP-Ab, HCV-Ab, or HBsAg.
  17. Clinically significant abnormal findings for RF, anti-dsDNA, ANA, or anti-CCP.
  18. Planned surgery (including cosmetic, dental, or oral surgery) or planned vigorous physical activity (including contact or collision sports) during the study.
  19. Planned blood donation during the study; planned receipt of any biologic agent within 3 months after study drug administration.
  20. Any condition that, in the investigator's judgment, makes the subject unsuitable for or unable to complete the study.
  21. Female-specific exclusions:

Oral contraceptive use within 30 days or planned during study; Long-acting estrogen/progestin injection, contraceptive patch, vaginal ring, subcutaneous implant, or contraceptive injection within 6 months; Unprotected intercourse within 14 days prior to randomization; Pregnancy or lactation; Plans for pregnancy, sperm/egg donation during the study or within 3 months after study completion

• UC Patients

  1. Crohn's disease (CD) or indeterminate colitis (IBD-U).

  2. Toxic megacolon, massive hemorrhage, perforation, sepsis, or intra-abdominal/peri-anal abscess requiring immediate surgical, endoscopic, or interventional treatment.

  3. History of ileostomy, proctocolectomy, or subtotal colectomy with ileorectal anastomosis.

  4. History of colorectal cancer, current CRC, serrated polyp with dysplasia, or atypical hyperplasia.

  5. Positive stool culture for pathogens or positive Clostridium difficile at screening. May be re-screened after adequate treatment and 30-day antibiotic washout.

  6. Clinically significant active infection; positive for HIV-Ab, TP-Ab, HCV-Ab, HBsAg (if HBsAg-negative but HBcAb-positive, add HBV-DNA; exclude if HBV-DNA > LLN), EBV-DNA, or CMV-DNA.

  7. Eosinophil count ≥ 2×ULN or diagnosed eosinophilia (including hereditary, primary, idiopathic, or secondary).

  8. Significant laboratory abnormalities:

     Hb < 80 g/L; WBC < 2.5×10⁹/L; Platelets < 100×10⁹/L; Clinically significant ECG abnormalities: PR ≥ 210 ms, QRS ≥ 120 ms, QTcF < 350 ms or ≥ 450 ms (Fridericia correction); Creatinine ≥ 1.5×ULN; Total bilirubin > 34.2 μmol/L; ALT or AST > 2×ULN; GGT > 2×ULN; Abnormal thyroid function (hyper- or hypothyroidism)

  9. Positive T-SPOT.TB.

  10. Receipt of another investigational drug within 5 half-lives prior to planned first SC dose.

  11. History of malignancy within 5 years.

  12. Uncontrolled angina or symptomatic congestive heart failure (NYHA class III or IV).

  13. Allergy to any component of the study drug.

  14. Pregnancy or lactation.

  15. Prior treatment with IL-2 class drugs; use of biologics or small molecules (e.g., anti-TNF, anti-IL-12/23, IL-23 inhibitors, vedolizumab, JAK inhibitors, S1P receptor modulators) within 8 weeks or 5 half-lives (whichever longer) prior to baseline; cyclosporine or tacrolimus within 2 weeks; rectal formulations planned during study; Chinese herbal medicine for UC within 2 weeks prior to baseline.

  16. Unable to comply with study protocol or withdraws informed consent.

  17. Other conditions unsuitable for participation per investigator's judgment.

  18. Receipt of any live vaccine within 2 months prior to screening, BCG within 12 months, or planned live vaccination during the study.