E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Diabetic retinopathy is a medical condition in which damage occurs to the retina due to diabetes mellitus. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012689 |
E.1.2 | Term | Diabetic retinopathy |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• Assess the effect of RG7774 on the severity of diabetic retinopathy
• Evaluate the safety and tolerability of RG7774 |
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E.2.2 | Secondary objectives of the trial |
• Assess the effect of RG7774 on progression to vision-threatening DR
• Assess the effect of RG7774 on visual acuity
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age >= 18 years
Ocular Criteria for study eye:
• Treatment naïve with moderately severe to severe Non-proliferative DR (NPDR) defined as Early Treatment Diabetic Retinopathy Study (ETDRS) DR severity score (DRSS) 47 or 53
• Patients are eligible with and without Diabetic Macular Edema (DME) in either eye, defined as the presence of signs in the macula such as swelling, leakage, exudates, cystoid changes and fluid. In addition, Central Subfield Thickness (CST) on SD OCT needs to be 300µm to confirm diagnosis of DME
• If present, DME has to be treatment-naïve and not expected to require treatment during the duration of the study in the opinion of the investigator at screening and Day 1
• Best corrected visual acuity (BCVA) score at screening of at least 70 letters in study eyes without DME and at least 75 letters in case DME is present, using ETDRS visual acuity testing charts at a testing distance of 4 meters
• Clear ocular media and adequate pupillary dilation to allow acquisition of good quality retinal images
General Criteria:
• Diagnosis of diabetic retinopathy type 1 or type 2, as defined by the World Health Organization and/or American Diabetes Association
• HbA1c <= 10%
• Allowed existing medication regimens should be stable for at least 6 weeks before screening, with the intent to remain stable throughout the study.
• Patient is willing to refrain from cannabinoid use for the entire duration of the study
• Women of child-bearing potential who are not pregnant or breastfeeding, agree to remain abstinent or use of two non-hormonal highly effective contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 4 weeks after the final dose of RG7774 or placebo
• Male participants, during the treatment period and for at least 90 days after the final dose of study treatment, agree to and remain abstinent or use barrier contraceptive measures such as a condom plus an additional contraceptive method and refrain from donating sperm for at least 90 days
• In the Investigator’s opinion, the subject is deemed appropriate for participation in the study, capable of following the study schedule of assessments and complying with the study restrictions and participation in the study or discontinuation of prohibited medication will not pose undue risks to the participant. |
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E.4 | Principal exclusion criteria |
Ocular criteria for Study eye:
• Prior treatment of the retina with laser or any intravitreal anti- Vascular endothelial growth factor (VEGF) or steroid. Focal laser in the retinal periphery due to other reasons than DR at least 3 months prior to screening is permitted.
• Prior periocular pharmacological intervention for other retinal diseases within 6 months prior to screening.
• Intraocular surgery less than 3 months prior to screening
• Aphakia or anterior chamber lens
• History of vitreoretinal surgery
• Uncontrolled glaucoma
• Amblyopia
• Any history of idiopathic or immune-mediated uveitis in either eye
• Any concurrent intraocular condition that in the opinion of the Investigator could reduce the potential for improvement, require medical surgical intervention or may confound the visual and functional assessment and interpretation of study results
Concurrent ocular conditions in either eye:
• Any active ocular infection.
• Any active intraocular inflammation.
General Criteria:
• Previous systemic use of anti-VEGF drugs within 6 months prior to screening
• Complications of diabetes such as end-stage renal disease or liver disease
• Currently untreated diabetes mellitus or previously untreated patients who initiated oral or injectable anti-diabetic medication within 3 months prior to screening.
• Uncontrolled blood pressure ([BP] defined as systolic > 180mmHg and/or diastolic >100 mmHg while patient at rest). If the BP is controlled by antihypertensive medication, the patient should be taking the same medication continuously for at least 30 days prior to screening.
• Confirmed clinically significant abnormality on ECG at screening. That includes but is not limited to QTcF > 450 ms for male participants and QTcF > 470 ms for female participants, absence of dominating sinus rhythm, AV-block II or III.
• History of coagulopathies, bleeding disorders or blood dyscrasias
• History of concurrent cardio-vascular disease not considered well controlled by the investigator
• Risk of suicidal behavior in the opinion of the Investigator or as evidenced by a “yes” to questions 4 and/or 5 of the Columbia Suicide Severity Rating Scale (C-SSRS) taken at screening, or any suicide attempt in the last 5 years
• Positive serology results for hepatitis B virus (HBV), hepatitis C virus (HCV), HIV-1, HIV-2
• Any major illness or major surgical procedure within one month before screening.
• History of or currently active other diseases, metabolic dysfunction, physical examination finding, and malignancies not considered cured, or clinical laboratory findings giving reasonable suspicion of a condition that contraindicated the use of the investigational medicinal drug or that might affect interpretation of the results of the study or renders the patient at high risk for treatment complications in the opinion of the investigator
• Known hypersensitivity to any of the excipients of the drug used, fluorescein dye or dilating eye drops
• Alcohol and/or substance abuse/dependence during the last 12 months
• Use of cannabinoids within 3 months prior to screening. One rescreening for this criterion is permitted
• Use of prohibited medications within 2 weeks prior to screening, or 5 half-lives (whichever is longer)
• Use of systemic medications known to be toxic to the lens, retina or optic nerve used during the 6-month period prior to screening or likely need to be used.
• Participation in an investigational drug or device study within 60 days prior to screening, or 5 half-lives (whichever is longer
• Blood donation or loss of blood > 500 mL within 3 months prior to screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Proportion of participants with >= 2 step improvement in the Early Treatment Diabetic Retinopathy Study DR severity score from baseline at Week 36 measured in the study eye
2. Frequency and severity of adverse events
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Baseline (Day 1) to Week 36
2. Up to 52 weeks |
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E.5.2 | Secondary end point(s) |
1. Incidence of anterior segment neovascularization, new proliferative diabetic retinopathy (PDR), new DME, and pre-existing DME requiring intervention
2. Change from baseline in best corrected visual acuity at Week 36 in the study eye
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to 52 weeks
2. Baseline to Week 36 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Portugal |
Slovakia |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study is defined as last visit of the last participant. The last participant last observation (LPLO) is expected to occur 48 weeks after the last participant is enrolled.
Participants are considered to have completed the study if they have completed all the assessments as required in this protocol |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |