E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetic retinopathy and diabetic maculopathy |
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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 | 20.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025425 |
E.1.2 | Term | Maculopathy |
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 |
The main objective of the LENS trial is to investigate whether treatment with fenofibrate can slow down the progression of diabetic retinopathy to a clinically significant level compared to treatment with placebo. |
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E.2.2 | Secondary objectives of the trial |
We will also investigate whether treatment with fenofibrate versus placebo has an effect upon: (i) progression to clinically significant retinopathy in specific groups of patients (e.g. men vs. women) (ii) the need for specialist treatment of retinopathy; this may include retinal laser treatment, surgery (a procedure called a vitrectomy to remove the jelly-like substance found in the eye), or a course of injections of medicine into the eye (iii) visual acuity (this is the quality of one's vision) (iv) questionnaires about one's quality of life (v) In addition, we will also assess whether using fenofibrate to treat patients with retinopathy is cost-effective for the NHS. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
i) Subjects capable of giving informed consent ii) Diabetes Mellitus (any type except gestational diabetes) iii) Age 18 years or above iv) Observable diabetic retinopathy (defined in the Scottish national retinopathy grading scheme as R2 and/or M1 in one/both eyes, or R1 in both eyes) at the patient's most recent retinal screening visit v) Willing to either complete electronic questionnaires or conduct telephone interviews for collection of questionnaire data once every 6 months |
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E.4 | Principal exclusion criteria |
i) Clinically significant DR (defined as R3 or R4 or M2 in one or both eyes) ii) History of gallbladder disease (cholecystitis, symptomatic gallstones, cholecystectomy) iii) History of acute or chronic pancreatitis iv) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2X the upper limit of normal (ULN) according to local NHS laboratory reference range v) Creatine kinase (CK) >3X ULN according to local NHS laboratory reference range vi) Estimated glomerular filtration rate (eGFR) <40mL/min/m2 at screening vii) Cirrhosis of any aetiology or any other serious hepatic disease (investigator opinion) viii) Female who is pregnant, breastfeeding, currently trying to become pregnant, or of child-bearing potential and not practicing birth control ix) Ongoing warfarin, cyclosporine, vitamin K antagonist (warfarin, phenindione, acenocoumarol), colchicine, ketoprofen, daptomycin or fibrate therapy x) Previous myositis or rhabdomyolysis of any cause, or diagnosed hereditary muscle disorder xi) Ongoing renal replacement therapy xii) Any previous organ transplant xiii) Previous reported intolerance to any fibrate xiv) Medical history that might limit the individual’s ability to take trial treatments for the duration of the study (e.g. severe respiratory disease, history of cancer within last 5 years other than non-melanoma skin cancer; or recent history of alcohol or substance misuse) xv) Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial |
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E.5 End points |
E.5.1 | Primary end point(s) |
The composite primary outcome is the development of clinically significant diabetic retinopathy (as defined in the retinal screening program) or any of the following treatments for retinopathy: retinal laser therapy, vitrectomy or intra-vitreal injection.
LENS will investigate the effect of allocation to fenofibrate versus placebo on progression to this composite primary outcome. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
LENS is a heavily streamlined trial which will collect outcome data from routinely collected health information (using linkage to registers) and from questionnaires, so there is no fixed timepoint for evaluation of this endpoint. However, it should be noted that retinal screening is offered every 6-12 months for patients with observale retinopathy in Scotland. And questionnaires will be conducted every 6-12 months. |
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E.5.2 | Secondary end point(s) |
1. The individual components of the composite primary outcome, i.e.: (i) Progression of to clinically significant retinopathy (ii) Retinal laser therapy for retinopathy (iii) Vitrectomy for retinopathy (iv) Intra-vitreal injection for retinopathy 2. Composite of retinal laser, vitrectomy or intra-vitreal injection for retinopathy 3. Any progression of retinopathy across Scotland's national retinopathy grading scale 4. Visual acuity (according to LogMAR or Snellen chart measurement conducted at retinal screening visits) 5. The development of hard exudates within 1 disc diameter of the macula 6. Visual function (according to the Visual Function Questionnaire [VFQ]-25 questionnaire, conducted once every 12 months) 7. Quality of life (according to the EQ-5D questionnaire, conducted once every 12 months) 8. Total cost to the health service (in terms of additional drug treatment and monitoring costs, and health care resource use over follow-up) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
LENS is a heavily streamlined trial which will collect outcome data from routinely collected health information (using linkage to registers) and from questionnaires, so there is no fixed timepoint for evaluation of most of these endpoints. However, it should be noted that retinal screening is offered every 6-12 months for patients with observale retinopathy in Scotland. And questionnaires will be conducted every 6-12 months. |
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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 | No |
E.6.5 | Efficacy | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | 2 |
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 | 11 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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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It is intended for the trial to continue until 222 primary events have occurred or until median follow up is at least 4 years, whichever is the later.
The ‘end of study’ is defined as the date on which the trial database is locked.
Given the streamlined nature of the trial where we are heavily reliant on receiving linkage data from various NHS sources, delays in receiving the data for the final linkage have been considered when deciding on this definition. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 31 |