Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05712720
Other study ID # RZ402-201
Secondary ID
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date February 6, 2023
Est. completion date May 2024

Study information

Verified date December 2023
Source Rezolute
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 100
Est. completion date May 2024
Est. primary completion date April 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Experimental: Group 1
RZ402 50 mg oral tablet, once daily for 3 months
Experimental: Group 2
RZ402 200mg oral tablet, once daily for 3 months
Experimental: Group 3
RZ402 400mg oral tablet, once daily for 3 months
Other:
Placebo: Group 4
Placebo, once daily for 3 months

Locations

Country Name City State
United States Rezolute Investigative Site, Augusta, Georgia Augusta Georgia
United States Rezolute Investigative Site, Austin, TX Austin Texas
United States Rezolute Investigative Site, Bakersfield, California Bakersfield California
United States Rezolute Investigative Site, Beverly Hills, California Beverly Hills California
United States Rezolute Investigative Site, Bloomfield, New Jersey Bloomfield New Jersey
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, Fullerton, California Fullerton California
United States Rezolute Investigative Site, Great Neck, New York Great Neck New York
United States Rezolute Investigative Site, Ladson, South Carolina Ladson South Carolina
United States Rezolute Investigative Site, Lenexa, Kansas Lenexa Kansas
United States Rezolute Investigative Site, Lynchburg, Virginia Lynchburg Virginia
United States Rezolute Investigative Site, McAllen, Texas McAllen Texas
United States Rezolute Investigative Site, Modesto, California Modesto California
United States Rezolute Investigative Site, New York, New York New York New York
United States Rezolute Investigative Site, Oak Forest, Illinois Oak Forest Illinois
United States Rezolute Investigative Site, Orlando, Florida Orlando Florida
United States Rezolute Investigative Site, Phoenix, Arizona Phoenix Arizona
United States Rezolute Investigative Site, Plano, Texas Plano Texas
United States Rezolute Investigative Site, Reno, Nevada Reno Nevada
United States Rezolute Investigative Site, Royal Oak, Michigan Royal Oak Michigan
United States Rezolute Investigative Site, Saint Louis, Missouri Saint Louis Missouri
United States Rezolute Investigative Site, San Antonio, Texas San Antonio Texas
United States Rezolute Investigative Site, Springfield, Illinois Springfield Illinois
United States Rezolute Investigative Site, Springfield, Oregon Springfield Oregon
United States Rezolute Investigative Site, Willow Park, Texas Willow Park Texas
United States Rezolute Investigative Site, Winter Haven, Florida Winter Haven Florida

Sponsors (1)

Lead Sponsor Collaborator
Rezolute

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Safety Events Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) 16 weeks
Primary Change in Central Subfield Thickness Change from baseline in Central Subfield Thickness (CST), as measured by Spectral Domain Ocular Coherence Tomography (SD-OCT), compared to placebo. 12 weeks
Secondary Change in BCVA Change from baseline in Best Corrected Visual Acuity (BCVA) in the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score, compared to placebo. 12 weeks
Secondary Change from baseline in Diabetic Retinopathy Severity Score (DRSS), compared to placebo. DRSS is scored on a range from 10 to 90 and where higher scores indicate a worse outcome. 12 weeks
Secondary Repeat-dose Cmax of RZ402 Repeat-dose Cmax of RZ402 16 weeks
Secondary Repeat-dose T1/2 of RZ402 Repeat-dose T1/2 of RZ402 16 weeks
Secondary Repeat-dose AUC of RZ402 Repeat-dose AUC of RZ402 16 weeks
See also
  Status Clinical Trial Phase
Completed NCT03953807 - A Study to Evaluate the Effectiveness and Safety of OZURDEX® in Patients With Diabetic Macular Edema But Never Treated Phase 4
Completed NCT03622580 - A Study to Evaluate the Efficacy and Safety of Faricimab (RO6867461) in Participants With Diabetic Macular Edema (YOSEMITE) Phase 3
Recruiting NCT06262737 - Single-center Study Measuring OSDI Dry Eye Score in Patients Undergoing an Anti-VEGF Induction Protocol
Terminated NCT04611152 - A Trial to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Participants With Diabetic Macular Edema (DME) Phase 3
Terminated NCT04603937 - A Study to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Participants With Diabetic Macular Edema (DME) Phase 3
Active, not recruiting NCT04108156 - This Study Will Evaluate the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Participants With Diabetic Macular Edema Compared With Intravitreal Ranibizumab Phase 3
Completed NCT02867735 - A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Activity of Intravitreal LKA651 in Patients With Macular Edema Phase 1
Withdrawn NCT03629210 - Combination OZURDEX® & EyLea® vs. OZURDEX® Monotherapy in IncompLete-Responders wIth Diabetic Macular Edema Phase 2
Withdrawn NCT02842541 - Safety Study of Intravitreal EBI-031 Given as a Single or Repeat Injection to Subjects With Diabetic Macular Edema Phase 1
Completed NCT02221453 - Cytokine Levels in Patients With Persistent Diabetic Macular Edema Treated With Triamcinolone Acetonide Phase 2
Completed NCT02979665 - Changes to the Retina Following Anti-VEGF Treatments for Diabetic Macular Edema
Completed NCT02556723 - Intravitreal Injections of Ziv-aflibercept for Macular Diseases N/A
Completed NCT02000102 - Outcomes of Diabetic Macula Edema Patients Switched to Aflibercept From Bevacizumab and/or Ranibizumab N/A
Completed NCT02088229 - Relating Retinal Structural and Functional Parameters to Visual Acuity in Eyes Undergoing Treatment for Diabetic Macular Edema N/A
Terminated NCT00779142 - Utility of Intravitreal Methotrexate in Diabetic Macular Edema Resistant to Conventional Therapies N/A
Completed NCT01171976 - Efficacy and Safety of Ranibizumab in Two "Treat and Extend" Treatment Algorithms Versus Ranibizumab As Needed in Patients With Macular Edema and Visual Impairment Secondary to Diabetes Mellitus Phase 3
Completed NCT00989989 - Efficacy and Safety of Ranibizumab (Intravitreal Injections) in Patients With Visual Impairment Due to Diabetic Macular Edema Phase 3
Completed NCT01259609 - Changes in Ciliary Body Thickness in Patients With Diabetic Macular Edema After Vitrectomy N/A
Completed NCT00683176 - Effect of Choline Fenofibrate (SLV348) on Macular Edema Phase 2
Terminated NCT00768040 - Efficacy of Aliskiren in the Treatment of Diabetic Macular Edema Phase 2