P2a Open Label Study to Evaluate 2-HPβCD in Subjects with Diabetic Kidney Disease

Phase 2

Not yet recruiting

• Conditions: Diabetic Kidney Disease
• Interventions: Drug: 2HPβCD

• Registration Number: NCT06489340
• Lead Sponsor: ZyVersa Therapeutics, Inc.

Brief Summary

This is an open label, two to three center study to evaluate the clinical efficacy and safety of 1 dose level of 2-hydroxypropyl-β-cyclodextrin (2-HPβCD) given intravenously in adult patients with type 2 diabetes with diabetic kidney disease (DKD) and proteinuria.

Detailed Description

This is a Phase 2a, open label, two to three center study to evaluate the clinical efficacy and safety of 1 dose level of 2-hydroxypropyl-β-cyclodextrin (2-HPβCD) given intravenously in adult patients with type 2 diabetes with diabetic kidney disease (DKD) and proteinuria.

The study will be conducted at 2 - 3 sites in the United States of America (USA) and will screen a sufficient number of subjects to complete 8 participants meeting the inclusion/exclusion criteria outlined.

The study consists of up to a 2-week screening period, a 12-week treatment period and a 4-week follow-up period.

Study Timeline

• Status Verified: 2024-06
• Study First Submitted: 2024-06-18
• Study First Submitted QC: 2024-06-28
• Study First Posted: 2024-07-05
• Last Update Submitted: 2025-01-21
• Last Update Posted: 2025-01-24
• Study Start: 2025-03-01
• Primary Completion: 2025-12-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

1. Capable of giving and has provided a signed Informed Consent Form (ICF).

2. Male or female age 18 to 75 years inclusive, at the time of signing the informed consent.

3. Women of childbearing potential (WOCBP) and male subjects who are partners of WOCBP must agree to use an acceptable form of contraception during the study and for 30 days following the last dose of study drug.

4. Clinical diagnosis of type 2 diabetes as per guidelines.

5. Clinical diagnosis of diabetic kidney disease in the opinion of the principal investigator, or renal biopsy proven diabetic kidney disease without evidence of additional pathologic findings of alternative diagnosis.

   1. At screening, based on two 24-hour urine collections, geometric mean of two urinary albumin creatine ratios (UACR) ≥ 400 mg/g and ≤ 3500 mg/g.
   2. At screening, based on two first morning void urine collections, mean UACR ≥ 400 mg/g and ≤ 3500 mg/g.
   3. At screening, eGFR equal or greater than 30 and less than 90 mL/min/1.73 m^2.

6. Body mass index (BMI) ≤ 40.0 kg/m^2.

7. If on diabetes and anti-hypertensive medications:

   1. Angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) inhibitors dose must be stable for 3 months before screening.
   2. Sodium-glucose co-transporter 2 (SGLT2) or GLP-1 receptor agonist or long-acting insulin dose must be stable for at least 3 months prior to screening.
   3. All other diabetes and anti-hypertensive medications must be at a stable dose for at least 3 months prior to screening.

8. Hemoglobin A1c (HbA1c) ≤10.0% at screening.

9. Willing to comply with IV administration of the study drug for 12 weeks and all protocol procedures during the study.

Exclusion Criteria

1. Has a solitary kidney.

2. Has a positive drug screen.

3. Known kidney disease other than diabetic kidney disease.

4. End stage renal disease (ESRD) (i.e., peritoneal dialysis, hemodialysis, or history of kidney transplantation).

5. Acute kidney injury or dialysis within the last 3 months before the screening visit.

6. Uncontrolled diabetes as defined by HbA1c >10 at screening.

7. Uncontrolled hypertension with systolic blood pressure (SBP) >140 mmHg or diastolic blood pressure (DBP) >90 mmHg during screening.

8. Unstable cardiovascular disease or history of myocardial infarction or arterial thromboembolic events within 3 months prior to screening or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease, or a QTc interval >480 msec.

9. Patients on IV medication containing cyclodextrin.

10. Patients on steroids.

11. Surgery within the past 3 months prior to the first study drug administration determined by the Investigator to be clinically relevant.

12. Known malignancy that is progressing or has required active treatment within the past 3 years. Any exceptions must be approved by the Medical Monitor.

    a. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.

13. Known history of Human Immunodeficiency Virus (HIV) infection (HIV 1/2 antibodies).

14. Known active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.

15. Diabetic ketosis, ketoacidosis and severe infections within a month or active infection requiring systemic therapy.

16. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participants' participation for the full duration of the study, or is not in the best interest of the participants to participate in the opinion of the treating Investigator.

17. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.

18. Women participants who are pregnant or breastfeeding or expecting to conceive children within the projected duration of the study or within 30 days of participation.

19. Aspartate aminotransferase (AST) or alanine transaminase (ALT) >3 upper limit of normal (ULN). One repeat test may be allowed within 7 days at the discretion of the Investigator.

20. Absolute neutrophil count ≤ 1.5 x 109/L at screening.

21. Platelets ≤ 100 x 109/L at screening.

22. Abnormal Hemoglobin (Hgb) (for men, abnormal levels are defined as <11.0 grams per deciliter (gm/dL) or >17.5 gm/dL. For women, < 10.0 gm/dL or >15.3 gm/dL.)

23. Currently participating or have participated in a study of an investigational product or used an investigational device within 3 months (or > 3 half-lives for mAbs with prolonged half-life of greater than 30 days) prior to the first dose of study intervention.

24. Patients on antibody therapeutics.

25. History or presence of alcohol or drug abuse within the 1 year prior to the first study drug administration.

26. A known history of otologic disease (e.g., Meniere's, sudden hearing loss, fluctuating hearing loss, vestibular schwannoma).

27. Pure tone air conduction thresholds in either ear at 3 consecutive frequencies > 60 dB at: 0.25, 0.5, 1, 2, 3, 4, 6, and 8 kHz.

28. Pure tone bone conduction thresholds > 60 dB in either ear that are 10 dB better than air conduction thresholds (i.e., air-bone gap > 10 dB) at all of the following frequencies: 0.5, 1, 2, and 4 kHz.

29. Use of non-steroidal anti-inflammatory drugs (NSAIDS) during the study period other than chronic low dose of aspirin stable for at least 3 months.

30. History of participation in a stem cell or gene therapy trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
2HPβCD	2HPβCD	Study drug will be administered by IV infusion during the treatment period.

Primary Outcome Measures

Name	Time	Method
Percent change in 24-hour urinary albumin to creatinine ratio (UACR)	From Day 1 (baseline) to Week 12 (end of treatment)	Percentage change in log-transformed urinary albumin to creatinine ratio (UACR) from day 1 (baseline) to week 12 (end of treatment)
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)	12 Weeks	Number of adverse events (AEs), serious adverse events (SAEs), discontinuations over the 12-week treatment period

Secondary Outcome Measures

Name	Time	Method
Population trough pharmacokinetics of 2-hydroxypropyl-β-cyclodextrin (2-HPβCD)	Day 1, Day 29, Day 57, Day 85	Trough plasma concentration of 2-hydroxypropyl-β-cyclodextrin (2-HPβCD) on Day 1, Day 29, Day 57, and Day 85, compared with pre-dosing concentrations on Day 1 and Day 4
Absolute change in 24-hour urinary protein to creatinine ratio (UPCR)	From Day 1 (baseline) to Week 12 (end of treatment)	Absolute change in log transformed 24 hour urinary protein to creatinine ratio (UPCR) from Day 1 (baseline) to Week 12 (end of treatment)
Effects of 2-HPβCD on hearing based on changes in pure tone air conduction threshold from Day 1 to Week 16, and percent changes in tinnitus, and sense of fullness or stuffiness in the ears based on a Hearing Monitoring Questionnaire	From Day 1 to Week 16	Changes in pure tone air conduction threshold based on audiometry testing from Day 1 to Week 16. Percent changes in the presence of tinnitus (ringing in the ears), and a sense of fullness or stuffiness in the ears based on responses to a Hearing Monitoring Questionnaire from Day 1 to Week 16
Absolute change in 24-hour urinary albumin to creatinine ratio (UACR)	From Day 1 (baseline) to Week 12 (end of treatment)	Absolute change in log transformed 24-hour urinary albumin to creatinine ratio (UACR) from Day 1 (baseline) to Week 12 (end of treatment)