Clinical trial NCT05712720: Study to Evaluate the Efficacy and Safety of RZ402 in Diabetic Macular Edema (DME)
Official title: A Randomized, Double-Masked, Placebo-Controlled, Parallel-Arm Study to Evaluate the Efficacy and Safety of RZ402 in Participants With Diabetic Macular Edema (DME)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Diabetic Macular Edema
Keywords: Diabetic Macular Edema
Diabetic Retinopathy
Diabetes
Retinal
Macular Thickening
Plasma Kallikrein Inhibitor
Lead sponsor: Rezolute
Sponsor class: OTHER
First posted: 2023-02-03
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

General Inclusion Criteria:

1. Confirmed diabetes mellitus Type 1 or Type 2
2. Stable glycemic control

   Study Eye Inclusion Criteria:
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.

   Fellow Eye Inclusion Criteria:
7. Best Corrected Visual Acuity ETDRS letter score at 4 meters of ≥5 letters at screening.

   Exclusion Criteria:

   Study Eye 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.

    Fellow Eye Exclusion Criteria:
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.

Primary outcomes:
measure: Safety Events
timeFrame: 16 weeks
measure: Change in Central Subfield Thickness
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in BCVA
timeFrame: 12 weeks
measure: Change from baseline in Diabetic Retinopathy Severity Score (DRSS), compared to placebo.
timeFrame: 12 weeks
measure: Repeat-dose Cmax of RZ402
timeFrame: 16 weeks
measure: Repeat-dose T1/2 of RZ402
timeFrame: 16 weeks
measure: Repeat-dose AUC of RZ402
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Rezolute Investigative Site, Phoenix, Arizona
state: Arizona
city: Bakersfield
country: United States
facility: Rezolute Investigative Site, Bakersfield, CA
state: California
city: Beverly Hills
country: United States
facility: Rezolute Investigative Site, Beverly Hills, California
state: California
city: Fullerton
country: United States
facility: Rezolute Investigative Site, Fullerton, California
state: California
city: Modesto
country: United States
facility: Rezolute Investigative Site, Modesto, California
state: California
city: Santa Barbara
country: United States
facility: Rezolute Investigative Site, Santa Barbara, CA
state: California
city: Coral Springs
country: United States
facility: Rezolute Investigative Site, Coral Springs, Florida
state: Florida
city: Deerfield Beach
country: United States
facility: Rezolute Investigative Site, Deerfield Beach, Florida
state: Florida
city: Fort Lauderdale
country: United States
facility: Rezolute Investigative Site, Fort Lauderdale, Florida
state: Florida
city: Orlando
country: United States
facility: Rezolute Investigative Site, Orlando, FL
state: Florida
city: Winter Haven
country: United States
facility: Rezolute Investigative Site, Winter Haven, Florida
state: Florida
city: Augusta
country: United States
facility: Rezolute Investigative Site, Augusta, Georgia
state: Georgia
city: Oak Forest
country: United States
facility: Rezolute Investigative Site, Oak Forest, Illinois
state: Illinois
city: Springfield
country: United States
facility: Rezolute Investigative Site, Springfield, IL
state: Illinois
city: Lenexa
country: United States
facility: Rezolute Investigative Site, Lenexa, KS
state: Kansas
city: Royal Oak
country: United States
facility: Rezolute Investigative Site, Royal Oak, MI
state: Michigan
city: Saint Louis Park
country: United States
facility: Rezolute Investigative Site, Saint Louis Park, MN
state: Minnesota
city: Saint Louis
country: United States
facility: Rezolute Investigative Site, Saint Louis, Missouri
state: Missouri
city: Reno
country: United States
facility: Rezolute Investigative Site, Reno, Nevada
state: Nevada
city: Bloomfield
country: United States
facility: Rezolute Investigative Site, Bloomfield, NJ
state: New Jersey
city: Great Neck
country: United States
facility: Rezolute Investigative Site, Great Neck, New York
state: New York
city: New York
country: United States
facility: Rezolute Investigative Site, New York, New York
state: New York
city: Springfield
country: United States
facility: Rezolute Investigative Site, Springfield, Oregon
state: Oregon
city: Ladson
country: United States
facility: Rezolute Investigative Site, Ladson, South Carolina
state: South Carolina
city: Austin
country: United States
facility: Rezolute Investigative Site, Austin, TX
state: Texas
city: Bellaire
country: United States
facility: Rezolute Investigative Site, Bellaire, TX
state: Texas
city: McAllen
country: United States
facility: Rezolute Investigative Site, McAllen, Texas
state: Texas
city: Plano
country: United States
facility: Rezolute Investigative Site, Plano, Texas
state: Texas
city: San Antonio
country: United States
facility: Rezolute Investigative Site, San Antonio, TX
state: Texas
city: The Woodlands
country: United States
facility: Rezolute Investigative Site, The Woodlands, TX
state: Texas
city: Willow Park
country: United States
facility: Rezolute Investigative Site, Willow Park, Texas
state: Texas
city: Lynchburg
country: United States
facility: Rezolute Investigative Site, Lynchburg, Virginia
state: Virginia
Study officials:
References: