E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Keratoconjunctivitis sicca (KCS), or dry eye syndrome |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10023350 |
E.1.2 | Term | Keratoconjunctivitis sicca |
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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 |
To demonstrate the superiority of NOVA22007 (CsA 0.1%) ophthalmic cationic emulsion, administered once daily versus Vehicle in patients with moderate to severe dry eye syndrome after a 6-month treatment period |
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E.2.2 | Secondary objectives of the trial |
To compare the ocular tolerance and systemic safety of NOVA22007 (CsA 0.1%) ophthalmic cationic emulsion administered once daily versus Vehicle in patients with moderate to severe dry eye syndrome, after a 6-month treatment period |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males or females 18 years of age or greater. 2. At baseline, moderate to severe dry eye condition persisting despite conventional management (which may include artificial tear drops, gels or ointments and punctual occlusion), and defined as the following: • At least one moderate to severe symptom of dry eye with a score ≥2 (severity graded on a 4-point scale) i.e., burning/stinging, foreign body sensation, itching, eye dryness, pain, blurred vision or sticky feeling and photophobia AND • Tear Break Up time ≤ 8 seconds AND • Corneal fluorescein staining ≥ 2 and ≤ 4 (modified Oxford scale, scale 0-5) AND • Schirmer tear test without anaesthesia of ≥ 2mm/5min and <10 mm/5min AND • Lissamine green staining > 4 (Van Bijsterveld scale, scale 0-9) The same eye (eligible eye) should fulfil all the above criteria. 3. Patient must provide written informed consent. 4. Patient must be willing and able to undergo and return for scheduled study-related examinations.
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E.4 | Principal exclusion criteria |
1. Best corrected distance visual acuity (BCDVA) score > + 0.7 Log Mar in the eligible eye. 2. Dry eye resulting from the destruction of conjunctival goblet cells or scarring. 3. Abnormal lid anatomy or blinking function. 4. Abnormalities of the nasolachrymal drainage system. 5. Presence or history of any systemic or ocular disorder or condition, including ocular surgery, trauma or disease that could possibly interfere with the interpretation of study results. 6. Any relevant ocular anomaly interfering with the ocular surface, including post radiation keratitis, Stevens-Johnson syndrome, corneal ulcer history or concomitant corneal ulcer of infectious origin, etc. 7. Any ocular surgery or laser (including palpebral, refractive and cataract surgery/laser) within 6 months before study entry in the eligible eye and within 3 months prior study entry in the non-eligible eye. 8. History of ocular trauma, infection (viral, bacterial, fungal), or ocular inflammation (Tyndall ≠ 0) as well as ocular inflammation signs not associated with KCS within the 3 months before the Screening Visit. 9. Patients with severe blepharitis not related to dry eye or Sjögren syndrome, acute lesions of rosacea and/or progressive pterygium. 10. Any other ocular diseases requiring topical ocular treatment during the study period. 11. Presence or history of ocular allergy (including seasonal conjunctivitis) or chronic conjunctivitis other than dry eye. 12. Active or history of ocular herpes. 13. History of malignancy in the last 5 years (with the exception of basal cell carcinoma and cervix carcinoma). 14. Systemic disease not stabilized within 1 month before the Screening Visit (e.g., diabetes with glycemia out of range, thyroid malfunction, uncontrolled autoimmune disease) or judged by the investigator to be incompatible with the study (e.g. current systemic infections) or condition incompatible with the frequent assessments needed by the study. 15. Known hypersensitivity to one of the components of the study or procedural medications (fluorescein, lissamine green, oxybuprocaine, etc.). 16. Presence or history of severe systemic allergy. 17. Any change within 1 month prior study entry of systemic medication that could affect a dry eye condition (e.g., estrogen-progesterone or other estrogen derivatives (only for post-menopausal women), antihistamines, tricyclic antidepressants, anxiolytics, antimuscarinics, beta-blocking agents, phenothiazines, omega-3, systemic corticosteroids etc…). These treatments are allowed during the study provided they remain stable throughout the course of the study. 18. Use of systemic or topical CsA (i.e., Restasis®), tacrolimus or sirolimus, within 6 months prior study entry. 19. Use of topical corticosteroids or prostaglandins within one month before study entry. 20. Any change within 1 month prior study entry of systemic pilocarpine, isotretinoine or tetracycline, as well as the use of topical pilocarpine or isotretinoine within 1 month before study entry. The systemic treatments (pilocarpine, isotretinoine or tetracycline) are allowed during the study provided they remain stable throughout the course of the study. 21. Use of topical antihistaminics, dual agents, betablocking agents or antibiotics within 2 weeks before study entry. 22. Any change in systemic immunosuppressant drugs within 1 month before study entry. 23. Any concomitant topical ocular treatment other than the study medications and concomitant tear substitute provided. 24. Contact lens wears during the study. 25. Anticipated use of temporary punctum plugs during the study. Prior punctal plugs are allowed provided they were inserted at least one month before study entry and they remain in situ during the study. 26. Any planned refractive surgery (LASIK, LASEK, PRK, etc) during the course of the study. 27. Pregnancy or lactation at study entry. 28. Women of childbearing potential not using a medically acceptable, highly effective method of birth control (such as implants, injectables or oral contraceptives together with condoms, some intra-uterine devices, sexual abstinence or vasectomised partner) throughout the conduct of the study up to two weeks after study end. The post-menopausal women (two years without menstruation) do not need to use any method of birth control. 29. Presence or history of drug addiction or alcohol abuse. 30. Patient who has participated in a clinical trial with a new active substance during the past month before study entry. 31.Participation in another clinical study at the same time as the present study.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Corneal fluorescein staining (on modified Oxford scale) • Patient’s global score of all symptoms of ocular discomfort unrelated to study medication instillation, using a visual analog scale (VAS) ranging from 0%–100% |
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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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.3 |
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 | 70 |
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 | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 25 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 25 |