Study to Evaluate Clinical Efficacy and Safety of Nuvastatic™ - C5OSEW5050ESA in Diabetic Retinopathy.

This is an interventional treatment trial for Diabetic Retinopathy Read More

Inclusion Criteria:

• • Type-2 Diabetes mellius (NIDDM) patients of both genders aged 18-65 years.

  • Able and willing to provide written informed consent.
  • Documented diagnosis of Type 2 diabetes mellitus a glycosylated hemoglobin A1c (HbA1c) of ≤ 12.0% at screening.
  • Patients preferably on oral medications for DM.
  • Meets specific ocular criteria for the study eye including but not limited to, the presence of non-proliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) in the study eye at screening with NPDR level 47 or level 53, as determined by the central reading center (CRC) by using the DR severity scale (DRSS), for which treatment can be deferred for at least 4 weeks after Day 1 visit.
  • Media clarity, pupillary dilation, and subject cooperation sufficient to obtain adequate assessments. (Subject has early treatment diabetic retinopathy study (ETDRS) best corrected visual acuity (BCVA) letter score ≤ 73 (Snellen 20/40) and ≥ 24 (Snellen 20/320) at screening visit).
  • Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.

Study Eye Inclusion Criteria

• Best corrected E-ETDRS visual acuity letter score ≥74 (i.e.20/32 or better) within 8 days of randomization.
• On clinical exam, definite retinal thickening due to DME within 3000 μm of the center of the macula but not involving the central subfield.

• Thickened non-central macular subfields on spectral domain OCT macular map that meet either of the following criteria:

  1. At least two non-central macular subfields with OCT thickness above threshold (average normal + 2 SD) from DRCR.net approved spectral domain OCT machines- see below.
  2. At least one non-central macular subfield with OCT thickness at least 15 μm above threshold (average normal + 2 SD) from DRCR.net approved spectral domain OCT machines-see DRCR.net procedures manual for threshold details.

• Central subfield thickness <250 microns obtained by one of the following DRCR.net approved spectral domain OCT machines:

  1. Zeiss Cirrus
  2. Heidelberg Spectralis
  3. Optovue RTVue
• Media clarity, pupillary dilation, and study participant cooperation sufficient for adequate OCT and fundus photographs.
• If the study participant is on multiple ocular drops, investigator believes that study participant can be compliant with a multi-drop regimen.

Exclusion Criteria:

• Insulin dependent Diabetes mellitus (IDDM or T1DM) patients.
• Any condition that would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease or glycemic control).
• History of myocardial infarction or other acute cardiac event.
• History of chronic renal failure requiring dialysis or kidney transplant.
• Prior participation in any clinical study.
• Treatment with any investigational study drug within 30 days of screening.
• Known allergy to study product.
• Treatment with specific prohibited medications or therapy beginning 4 weeks prior to screening and throughout the duration of the study.
• Subject with macular edema considered to be due to a cause other than DME, decrease in BCVA due to causes other than DME, significant macular ischemia, any other ocular disease that may cause substantial reduction in BCVA, active peri-ocular or ocular infection.
• Subject with an history of following within 3 months prior to Day 1: non-infectious uveitis, high myopia (-8 diopter or more correction), pars plana vitrectomy, any ocular surgery, prior IVT, subtenon, or periocular, non-sustained release, steroid therapy, uncontrolled glaucoma,
• History of systemic anti-VEGF or pro-VEGF treatment within 4 months prior to randomization.
• Any laboratory abnormalities at screening.
• Male subjects who are not surgically sterile and are not willing to practice a medically accepted method of birth control with their female partner of childbearing potential from screening through 30 days following completion of the study
• Female subjects of childbearing potential who are not willing to practice a medically accepted method of birth control with their non-surgically sterile male sexual partner from screening through 30 days following completion of the study
• Female subjects who are pregnant or lactating.
• Subject has media clarity, papillary constriction (i.e., senile miosis), or subject lacks cooperation that would interfere with any study procedures, evaluations or interpretation of data.
• Cataract surgery performed within 6 months prior to screening or planned during the trial; or any additional eye disease in the study eye that, in the opinion of the investigator, could compromise or alter visual acuity during the course of the study (e.g. vein occlusion, uncontrolled intraocular pressure (IOP) >24 mmHg on optimal medical treatment, glaucoma with visual field loss, uveitis or other ocular inflammatory disease, vitreomacular traction, monocular vision, history of ischemic optic neuropathy, or genetic disorders such as retinitis pigmentosa)
• Active center-involved DME (CI-DME) on clinical examination and Optical Coherence Tomography (OCT) central subfield thickness in the study eye above 300 μm as measured by Optovue OCT or above 320 μm as measured by Heidelberg OCT
• Anterior segment and vitreous abnormalities in the study eye that would compromise the adequate assessment of the best corrected visual acuity or an adequate examination of the posterior pole
• Evidence of neovascularization on clinical examination including active neovascularization of the iris (small iris tufts are not an exclusion) or angle neovascularization in the study eye, ruled out by gonioscopy (documented in the last 4 weeks before screening or performed at screening)
• Prior pan-retinal photocoagulation (defined as ≥ 100 burns placed previously outside of the posterior pole) in the study eye
• History of DME or DR treatment with macular laser within 3 months prior to screening, or intraocular injections of medication within 6 months prior to screening, and no more than 4 prior intraocular injections in the study eye at any time in the past
• Patients treated with Monoamine Oxidase (MAO) inhibitors or drugs that may have potential side effects due to MAO inhibition
• Current or planned, during the trial, use of medications known to be toxic to the retina, lens or optic nerve, or cause vision loss
• Patients who must or wish to continue the intake of other restricted medications or any drug considered likely to interfere with the safe conduct of the trial
• Estimated Glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at screening, or where the investigator expects filtration rate is likely to drop below 60 mL/min/1.73m2 during the trial
• Alanine transaminase (ALT) or aspartate transaminase (AST) greater than 2.0-fold the upper limit of normal, or total bilirubin > 1.5x upper limit of normal.
• Uncontrolled arterial hypertension defined as a single measurement of systolic blood pressure >180 mmHg, or two consecutive measurements of systolic blood pressure > 160 mmHg and/or diastolic blood pressure >100 mmHg on optimal medical regimen at screening. If blood pressure is brought to ≤ 160/100 mmHg by antihypertensive treatment until randomization, individual can become eligible.
• Wolff-Parkinson-White Syndrome, baseline QTc > 450 ms, family history of long QT, or on medication prolonging QT time at screening or planned initiation during the trial
• Diagnosis of a serious or unstable systemic or eye disease and other conditions that, in the clinical judgment of the investigator, are likely to interfere with the analyses of safety and efficacy in this study. Patients with an expected life expectancy of less than 2 years are also excluded.
• Active known or suspected chronic or relevant acute infections, such as HIV (Human Immunodeficiency Virus)\viral hepatitis, or tuberculosis. QuantiFERON® TB test and HBs Ag test will be performed during screening. Patients with a positive test result may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active infection.
• Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix.
• Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable study participant or unlikely to complete the trial
• Known hypersensitivity to any component of the trial drug and/or allergy to fluorescein dye
• Major surgery (major according to the investigator's assessment) performed within 12 weeks prior to randomization or planned during the trial, e.g. hip replacement
• Currently enrolled in another investigational drug trial, or less than 30 days or 5 times half-life of the investigational drug, whichever is longer, since ending another investigational drug trial from the screening visit in this trial or receiving other investigational treatment(s); patients participating in a purely observational trial will not be excluded.
• Previous randomization in this trial
• Women who are pregnant, nursing, or who plan to become pregnant while in the trial
• Any other clinical condition that, in the opinion of the investigator, would jeopardize patient safety while participating in this clinical trial.