Study to Evaluate the Efficacy and Safety of RZ402 in Diabetic Macular Edema (DME)

NCT ID: NCT05712720

Last Updated: 2025-10-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-06
• Study Completion Date: 2024-04-11

Brief Summary

The objective of this trial is to assess the safety, efficacy, and tolerability of RZ402 in patients with Diabetic Macular Edema.

Detailed Description

Diabetic macular edema (DME) is a common retinal microvascular complication in diabetic patients that can lead to progressive loss of visual acuity and ultimately to complete vision loss. DME is the main cause of vision loss in patients with Type 2 diabetes. There is a significant unmet medical need to develop better therapies of DME and diabetic retinopathy (DR). RZ402 is a potent and selective plasma kallikrein inhibitor (PKI), which is being developed as an oral therapy for the chronic treatment of DME and DR.

This is a Phase 2, Randomized, Double-Masked, Placebo-Controlled, Parallel-Arm Study to Evaluate the Efficacy and Safety of RZ402 in Participants with Diabetic Macular Edema (DME). A screening period of up to 4 weeks will evaluate eligibility. Once enrolled, patients will be randomized with a 1:1:1:1 ratio to receive RZ402 or placebo for up to 12 weeks. After completing dosing, the patient will enter into a 4 week follow up period.

Conditions

Diabetic Macular Edema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group 1 - 50 mg RZ402

RZ402 50mg oral tablet, once daily for 3 months

Group Type: EXPERIMENTAL

Experimental: Group 1 - 50mg RZ402

Intervention Type: DRUG

RZ402 50 mg oral tablet, once daily for 3 months

Group 2 - 200 mg RZ402

RZ402 200mg oral tablet, once daily for 3 months

Group Type: EXPERIMENTAL

Experimental: Group 2 - 200mg RZ402

Intervention Type: DRUG

RZ402 200mg oral tablet, once daily for 3 months

Group 3 - 400 mg RZ402

RZ402 400mg oral tablet, once daily for 3 months

Group Type: EXPERIMENTAL

Experimental: Group 3 - 400mg RZ402

Intervention Type: DRUG

RZ402 400mg oral tablet, once daily for 3 months

Group 4 - Placebo

placebo oral tablet, once daily for 3 months

Group Type: PLACEBO_COMPARATOR

Placebo: Group 4 - Placebo

Intervention Type: OTHER

Placebo oral tablet, once daily for 3 months

Interventions

Experimental: Group 1 - 50mg RZ402

RZ402 50 mg oral tablet, once daily for 3 months

Intervention Type: DRUG

Experimental: Group 2 - 200mg RZ402

RZ402 200mg oral tablet, once daily for 3 months

Intervention Type: DRUG

Experimental: Group 3 - 400mg RZ402

RZ402 400mg oral tablet, once daily for 3 months

Intervention Type: DRUG

Placebo: Group 4 - Placebo

Placebo oral tablet, once daily for 3 months

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Confirmed diabetes mellitus Type 1 or Type 2

2. Stable glycemic control

3. Mild to moderate non-proliferative diabetic retinopathy (NPDR) with retinal thickening due to CI-DME as determined by the Investigator.

4. Spectral Domain Optical Coherence Tomography (SD-OCT) foveal CST at screening measuring ≥320 µm (or corresponding values)

5. Best Corrected Visual Acuity ETDRS letter score at 4 meters of ≤78 letters at screening.

6. Media clarity, pupillary dilation, and participant cooperation sufficient for adequate clinical evaluations, OCT images and fundus photographs, at screening.

7. Best Corrected Visual Acuity ETDRS letter score at 4 meters of ≥5 letters at screening.

Exclusion Criteria

8. Received more than 3 anti-VEGF injections (including Avastin) and/or received a recent anti-VEGF injection within 8 weeks of Randomization.

9. Any history of retinal surgery or other surgical intervention for DME.

10. Intraocular surgery (including cataract surgery), within 12 weeks prior to Randomization, or anticipated need for ocular surgery during the study period.

11. History of trabeculectomy or other filtration surgery (prior laser trabeculoplasty and placement of iStent®1 in conjunction with cataract surgery is permitted if the procedure took place ≥12 weeks prior to Randomization).

12. Autoimmune idiopathic inflammatory eye disease such as anterior uveitis, or participants with history or signs of chronic inflammation.

13. Full thickness macular hole or retinal detachment.

14. Panretinal, macular focal, or grid laser photocoagulation within 16 weeks of Randomization or anticipated need for the use of laser photocoagulation during the study period.

15. Uncontrolled glaucoma, at screening, defined as IOP ≥25 mmHg.

16. The use of corticosteroids as follows:

1. Topical corticosteroids within 12 weeks prior to Randomization and throughout the remainder of the study.

2. Use of intraocular or sub-Tenon's steroids within 2 years of Randomization in phakic eyes or 9 months of Randomization in pseudophakic eyes, and throughout the remainder of the study.

17. Intraocular or sub-Tenon's steroid injection within 6 months of Randomization and throughout the remainder or the study.

General Exclusion:

18. Use of the following medications or substances within the specified timeframes below and throughout the remainder of the study.

a. Within 16 weeks of Randomization: i. Systemic anti-VEGF or pro-VEGF treatments ii. Systemic, approved, or off-label drugs or devices used to treat DME iii. Participated in an investigational drug or device study within 16 weeks or 5 half-lives (whichever is longer) of Randomization, including systemic or ocular studies iv. Initiation of drugs or substances known to improve or worsen macular edema e.g., Latanoprost or phosphodiesterase-5 (PDE-5) inhibitors (e.g., Sildenafil or others in PDE-5 class), but participants may remain on these drugs if they were initiated >16 weeks prior to Randomization.

b. Within 12 weeks of Randomization: i. Use of tobacco- or nicotine- containing products (e.g., cigarettes, cigars, chewing tobacco, snuff, vaping).

c. Within 4 weeks of Randomization: i. Anti-coagulants, except for aspirin ≤325 mg/day and/or clopidogrel ≤75 mg/day (or equivalent drug class) ii. Total daily doses of Metformin >1000 mg iii. Total daily doses of niacin (Vitamin B3) >1.5 g/day iv. Use of systemic steroids at supraphysiologic doses (e.g., prednisone equivalent of 5 mg/day or hydrocortisone equivalent of 20 mg/day).

v. Drugs that may affect the retina or optic nerve such as quinolones, thioridazine, deferoxamine, ethambutol, vigabatrin, and pentosan.

19. Alanine aminotransferase (ALT), or aspartate aminotransferase (AST), or alkaline phosphatase (ALP) ≥2X upper limit of normal (ULN), total bilirubin ≥1.5X ULN, or gamma-glutamyl transferase (GGT) ≥3X ULN as per the central laboratory.

20. Estimated glomerular filtration rate (eGFR) at ≤45 mL/min and/or history of persistent micro or macro albuminuria.

21. History of current or prior (within 1 year of Randomization) any significant illness, or any medical history

22. History of bariatric surgery or other surgical or medical history

23. History of current or prior (within 1 year of Randomization) abnormal, clinically significant ECG including inadequately controlled hypertension

24. History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding.

25. Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury

26. Known history of human immune-deficiency virus (HIV), hepatitis C, or hepatitis B infection.

27. Malignancies within 3 years prior to Randomization

28. Donated more than 500 mL of blood or significant blood loss within 60 days before Randomization.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rezolute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Rezolute Investigative Site, Phoenix, Arizona

Phoenix, Arizona, United States

Rezolute Investigative Site, Bakersfield, CA

Bakersfield, California, United States

Rezolute Investigative Site, Beverly Hills, California

Beverly Hills, California, United States

Rezolute Investigative Site, Fullerton, California

Fullerton, California, United States

Rezolute Investigative Site, Modesto, California

Modesto, California, United States

Rezolute Investigative Site, Santa Barbara, CA

Santa Barbara, California, United States

Rezolute Investigative Site, Coral Springs, Florida

Coral Springs, Florida, United States

Rezolute Investigative Site, Deerfield Beach, Florida

Deerfield Beach, Florida, United States

Rezolute Investigative Site, Fort Lauderdale, Florida

Fort Lauderdale, Florida, United States

Rezolute Investigative Site, Orlando, FL

Orlando, Florida, United States

Rezolute Investigative Site, Winter Haven, Florida

Winter Haven, Florida, United States

Rezolute Investigative Site, Augusta, Georgia

Augusta, Georgia, United States

Rezolute Investigative Site, Oak Forest, Illinois

Oak Forest, Illinois, United States

Rezolute Investigative Site, Springfield, IL

Springfield, Illinois, United States

Rezolute Investigative Site, Lenexa, KS

Lenexa, Kansas, United States

Rezolute Investigative Site, Royal Oak, MI

Royal Oak, Michigan, United States

Rezolute Investigative Site, Saint Louis Park, MN

Saint Louis Park, Minnesota, United States

Rezolute Investigative Site, Saint Louis, Missouri

St Louis, Missouri, United States

Rezolute Investigative Site, Reno, Nevada

Reno, Nevada, United States

Rezolute Investigative Site, Bloomfield, NJ

Bloomfield, New Jersey, United States

Rezolute Investigative Site, Great Neck, New York

Great Neck, New York, United States

Rezolute Investigative Site, New York, New York

New York, New York, United States

Rezolute Investigative Site, Springfield, Oregon

Springfield, Oregon, United States

Rezolute Investigative Site, Ladson, South Carolina

Ladson, South Carolina, United States

Rezolute Investigative Site, Austin, TX

Austin, Texas, United States

Rezolute Investigative Site, Bellaire, TX

Bellaire, Texas, United States

Rezolute Investigative Site, McAllen, Texas

McAllen, Texas, United States

Rezolute Investigative Site, Plano, Texas

Plano, Texas, United States

Rezolute Investigative Site, San Antonio, TX

San Antonio, Texas, United States

Rezolute Investigative Site, The Woodlands, TX

The Woodlands, Texas, United States

Rezolute Investigative Site, Willow Park, Texas

Willow Park, Texas, United States

Rezolute Investigative Site, Lynchburg, Virginia

Lynchburg, Virginia, United States

Countries

United States

Other Identifiers

RZ402-201

Identifier Type: -

Identifier Source: org_study_id