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 |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054109 |
E.1.2 | Term | Non-proliferative diabetic retinopathy |
E.1.2 | System Organ Class | 100000015258 |
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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 |
The main objective is to evaluate ocular and systemic safety and tolerability of BI 1467335 as
well as whether BI 1467335 monotherapy has a potential to improve retinal lesions in
patients with moderately severe NPDR (DRSS level 47) or severe NPDR (DRSS level 53),
without CI-DME. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Of full age (according to local legislation, usually ≥ 18 years) and ≤ 80 years at screening
2. Male or female patients. Women of childbearing potential (WOCBP)1 must be ready and
able to use two methods of contraception with at least one of them being a highly
effective method of birth control per ICH M3 (R2) that result in a low failure rate of less
than 1% per year when used consistently and correctly. A list of contraception methods
meeting these criteria is provided in the patient information.
3. Diagnosis of diabetes mellitus (type 1 or type 2):
- Documented diabetes by American Diabetes Association (ADA) and/or World Health
Organization criteria
- Antidiabetic medication stable for ≥3 months prior to screening and expected to be
stable throughout the trial (no change in medication or the dose, except for insulin the
prescribed total daily dose change not more than 10%)
4. Glycosylated hemoglobin (HbA1c) ≤ 10% at screening
5. 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 CRC by using the DR severity scale (DRSS)
6. Best corrected visual acuity ETDRS letter score ≥ 70 letters in the study eye at screening
7. Media clarity, pupillary dilation and individual cooperation sufficient for adequate retinal
examination including fundus photographs and OCT
8. Signed and dated written informed consent in accordance with ICH-GCP and local
legislation prior to admission to the trial |
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E.4 | Principal exclusion criteria |
1. 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)
2. Active center-involved DME (CI-DME) on clinical examination and OCT central
subfield thickness above 300 μm in the study eye, as measured by Optovue OCT
3. 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
4. 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)
5. Prior pan-retinal photocoagulation (defined as ≥ 100 burns placed previously outside of
the posterior pole) in the study eye
6. 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
7. Patients treated with Monoamine Oxidase B (MAO-B) inhibitors (see Section 4.2.2.1) at
the time or up to 3 months prior to randomization or planned initiation during the trial
8. Current or planned, during the trial, use of medications known to be toxic to the retina,
lens or optic nerve, or cause vision loss
Further criteria apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) proportion of patients with any ocular adverse events (according to Common Terminology Criteria for Adverse Events (CTCAE) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1) Proportion of patients with at least 2 steps improvement in the study eye on the DRSS at week 12 compared to baseline.
2) The proportion of patients with adverse events other than ocular adverse events over the on treatment period (over 24 weeks) (according to CTCAE). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
France |
Germany |
Greece |
Italy |
Norway |
Spain |
United Kingdom |
United States |
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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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |