Phase IIb Clinical Trial for the Efficacy and Safety by CU01-1001 for 24 Weeks in Type 2 DM Patients With Albuminuria

A Multi-center, Randomized, Double-blinded, Placebo-controlled, Parallel Phase IIb Clinical Trial for the Efficacy Assessment and Safety Evaluation by Treating CU01-1001 for 24 Weeks in Type 2 Diabetic Nephropathy Patients With Albuminuria

To evaluate the efficacy and safety of CU01-1001 administered for 24 weeks in type 2 diabetic nephropathy patients with albuminuria.

Inclusion Criteria:

1. Male/female patients aged ≥ 30 years
2. Patients diagnosed with type 2 diabetes prior to screening
3. Patients who have been receiving a stable dose of either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) for at least 8 weeks prior to screening
4. Patients who experienced albuminuria defined as a urine albumin-to-creatinine ratio (UACR) ≥ 100 mg/g within 52 weeks prior to screening, and with UACR between 100 and 1000 mg/g at the time of screening
5. Patients with blood pressure ≤ 140/90mmHg at screening
6. Patients with 25 ≤ estimated glomerular filtration rate (eGFR) ≤ 75ml/min/1.73m2 at screening
7. Patients with HbA1c ≤ 9.0% at screening

Exclusion Criteria:

1. Patients with a history of acute kidney injury (AKI) within 12 weeks prior to screening, or with an increase in serum creatinine (SCr) ≥ 0.3 mg/dL within 48 hours, or an increase to ≥ 1.5 times the baseline (lowest value within the prior 12 weeks)

2. Patients with a history or current diagnosis of heart failure classified as New York Heart Association (NYHA) Class III or IV, or a history of hospitalization due to heart failure

3. Patients with renal disease, including but not limited to:

   • Non-diabetic kidney disease
   • Urological disorders
   • Nephrotic syndrome

4. Patients with a history of hepatic disease or meeting any of the following criteria related to liver function:

   • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN)
   • Total bilirubin > 3 × ULN

5. Patients with a white blood cell (WBC) count < 2 × 10³/µL

6. Patients with a lymphocyte count < 0.5 × 10⁹/L

7. Patients with hemoglobin < 9 g/dL

8. Patients with organic gastrointestinal disorders or chronic gastrointestinal diseases associated with clinically significant malabsorption at screening, including but not limited to:

   • Short bowel syndrome
   • Active Crohn's disease
   • Ulcerative colitis

9. Patients with a clinically significant infection requiring treatment at the time of screening

10. Patients who, within 12 weeks prior to informed consent, have been diagnosed with or undergone treatment/procedures for the following cardiovascular conditions:

    • Unstable angina pectoris
    • Myocardial infarction
    • Transient ischemic attack (TIA)
    • Cerebrovascular accident (stroke)
    • Peripheral vascular disease, or
    • Have undergone coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA)

11. Patients who have received any of the following prohibited concomitant medications within 4 weeks or within 5 half-lives (whichever is longer) prior to screening:

(1) Fumaric acid derivatives other than the investigational product (2) Diuretics, including:

• Thiazide (e.g., hydrochlorothiazide)
• Loop (e.g., furosemide)
• Potassium-sparing agents (e.g., spironolactone) (3) Lipid-lowering agents, including fibrates and nicotinic acid (4) Interferon beta-1α, anticancer agents, immunosuppressants, live vaccines, or nephrotoxic drugs (e.g., aminoglycosides, NSAIDs excluding acetylsalicylic acid, lithium) (5) Any other medications that, in the opinion of the investigator, may affect the investigational product 12) Patients with a history of alcohol or substance abuse 13) Patients with a known hypersensitivity to the investigational product or any of its components 14) Patients with a planned initiation of dialysis or kidney transplantation within 36 weeks (9 months) 15) Patients who are anticipated to have poor compliance with a protein-restricted diet and administration of the investigational product 16) Pregnant or breastfeeding women 17) Patients of childbearing potential who are unwilling to agree to the use of acceptable methods of contraception as specified in this protocol, and therefore are at risk of pregnancy.

Female subjects of childbearing potential who have not undergone surgical sterilization must have a negative pregnancy test prior to participation and must agree to use highly effective contraception throughout the study period 18) Patients who have participated in another clinical trial within 12 weeks prior to screening 19) Patients who are deemed unsuitable for participation in this clinical trial at the discretion of the investigator or sub-investigator