AP303 safety, tolerability, and dosing in people with diabetic kidney disease

A Randomized, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AP303 Following 2-week Oral Administration in Diabetic Kidney Disease Patients With Renal Impairment.

This study will try a 2-week oral dose of AP303 or placebo in adults with type 2 diabetic kidney disease to see if it is safe and how the body processes it.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 30 Years and up
• Sex: All
• Sponsor: Alebund Pharmaceuticals (Industry-sponsored)
• Drugs / interventions: immunotherapy, cyclophosphamide
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06666283 on ClinicalTrials.gov

What this trial studies

This is a single-center, double-blind, randomized, placebo-controlled Phase 1 study testing two dose cohorts of AP303 given orally for two weeks in people with diabetic kidney disease. Each cohort enrolls nine participants randomized 2:1 to receive AP303 or matching placebo (six active, three placebo). The primary focus is on safety and tolerability, with detailed pharmacokinetic (PK) and pharmacodynamic (PD) measurements collected over the dosing and follow-up period. Eligible participants have type 2 diabetes with moderate reductions in kidney function (eGFR 30–59 mL/min/1.73 m²) and elevated urinary albumin-to-creatinine ratio, and must be on stable glucose-lowering therapy and stable ACE inhibitor or ARB therapy.

Who should consider this trial

Good fit: Adults aged 30 or older with type 2 diabetes, BMI 18–30 kg/m², eGFR between 30 and 59 mL/min/1.73 m², urinary albumin-to-creatinine ratio ≥30 mg/g, and on stable glucose and ACE inhibitor/ARB therapy are the intended participants.

Not a fit: People with other forms of chronic kidney disease, eGFR below 30 or above 59 mL/min/1.73 m², unstable diabetes medication regimens, current immunosuppressive therapy, or BMI outside 18–30 kg/m² are unlikely to be eligible or benefit from this study.

Why it matters

Potential benefit: If AP303 is safe and shows favorable PK/PD, it could advance to later trials and eventually become a new treatment option that helps protect kidney function in people with diabetic kidney disease.

How similar studies have performed: Early-phase trials of novel agents for diabetic kidney disease have sometimes shown promising safety and biomarker changes, but many approaches remain exploratory and few have yet produced transformational clinical benefits.

Eligibility criteria

Inclusion Criteria:

1. Male and female participants, ≥30 years of age at the time of signing the informed consent form.
2. BMI (body mass index) 18-30 kg/m².
3. Patient has a clinical diagnosis of Type 2 Diabetes Mellitus and is taking at least one type of hypoglycemic drugs, before screening visits, the doses of hypoglycemic drugs, including insulin, need to be stable for at least two weeks..
4. Patient must be on a stable dose of angiotensin converting anzyme inhibitior (ACEI) or Angiotensin II receptor blockers (ARB) for at least 4 weeks prior to screening.
5. Hemoglobin A1c ≥6.5% but ≤10.5% at the screening visit.
6. Estimated GFR ≥30 mL/min/1.73m² but \< 60 mL/min/1.73m² at the screening visit.
7. Urinary albumin to creatinine ratio ≥ 30 mg/g at the screening visit.

Exclusion Criteria:

1. Chronic kidney disease other than type 2 diabetic kidney disease.
2. Patient receiving corticosteroid immunotherapy or other immunosuppressants (such as calcineurin inhibitors ciclosporin, cyclophosphamide, or mycophenolate mofetil) in the past 3 months before screening.
3. Recently having acute kidney injury or received renal surgery within the last 6 months before screening visit, or have received renal transplantation.
4. Congestive heart failure classified New York Heart Association (NYHA) class II to IV within the last 3 months before the screening visit.
5. Peripheral edema above the ankle level at the screening or randomization visit.
6. Confirmed (based on the average of 2 separate resting blood pressure measurements in a sitting position, after at least 5 minutes rest) systolic BP greater than 160 or less than 90 mmHg, and diastolic BP greater than 100 or less than 50 mmHg at screening.
7. Myocardial infarction, acute coronary syndrome, stroke or transient ischemic attack, cardiovascular surgery within 6 months prior to the screening visit.
8. Abnormalities of ECG parameters and abnormal shape of ECG wave on screening ECG: e.g.

   * QTc interval (QTcF \> 450 ms for male and QTcF \> 470 ms for female) based on the average interval on triplicate ECGs obtained after 5 minute's rest in a supine position
   * Notable resting bradycardia (mean HR \< 40 bpm)
   * Notable resting tachycardia (mean HR \> 100 bpm)
   * ECG with QRS and/or T wave judged to be unfavorable for a consistently accurate QT measurement (e.g., neuromuscular artifact that cannot be readily eliminated, indistinct QRS onset, low amplitude T wave, merged T- and U-waves, prominent U waves)
   * Any other significant abnormality
9. Implantation of cardiac pacemaker or clinically significant arrhythmia, e.g. atrial fibrillation, atrial flutter, right or left bundle branch block, Wolf-Parkinson-White Syndrome.
10. Current or previous treatment with a thiazolidinedione (e.g., medications containing pioglitazone or rosiglitazone, like Actos, Avandia, ActoplusMet, Avandamet, Avandaryl), PPARa agonist (like fenofibrate) or any dual/multiple PPARa/g agonist (e.g., Chiglitazar Sodium) in the 3 months preceding screening visit.
11. Previous treatment with CYP2C8 inducer or strong/moderate inhibitor (refer to the list in Appendix 4) in the 1 month preceding screening visit.
12. Chronic therapy with non-steroidal anti-inflammatory drugs (NSAIDs) (except prophylactic stable low dose aspirin, defined as its dose not higher than 100 mg daily; paracetamol/acetaminophen was allowed) in the last month before screening.
13. ALT or AST \>1.5 × ULN, or laboratory tests revealed other clinically significant abnormalities in liver function at screening.
14. Creatine phosphokinase (CPK) elevated \> 3 x ULN at screening visit or history of drug-induced myopathy.
15. History of malignancy within 5 years before screening (exceptions: squamous and basal cell carcinomas of the skin and carcinoma of the cervix in situ, or a malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence).
16. Participants who have had significant acute infection, e.g., COVID-19, influenza, local infection, acute gastrointestinal symptoms or any other clinically significant illness within two weeks before study drug administration.
17. Positive test at screening of any of the following: Hepatitis B (HBsAg), Hepatitis C (HCVAb), human immunodeficiency virus (HIV Ab) or syphilis AB.
18. Dosed with a small-molecule investigational drug within 3 months, or biologic investigational drug within 3 months or 5 half-lives (whichever is the longer) prior to first dose of this study.
19. History of drug and/or alcohol abuse or addiction. History (within 3 months of screening) of alcohol consumption exceeding 3 and 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol) for male and female, respectively.
20. Within 2 weeks prior to admission, use of \>5 cigarettes or equivalent nicotine-containing product per day.
21. Medical or social conditions that would potentially interfere with the participant's ability to comply with the study visit schedule or the study assessments.

Where this trial is running

Beijing, Beijing Municipality

• Peking University First Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Principal investigator: Hong Zhang — Peking University First Hospital
• Study coordinator: Yuran Zhang

Conditions Diabetic Kidney Disease