| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderate-to-severe Dry Eye disease |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10013774 |
| E.1.2 | Term | Dry eye |
| E.1.2 | System Organ Class | 10015919 - Eye disorders |
|
| 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 |
Determine the efficacy of oral CF101, as compared to placebo, when administered at doses of either 0.1 mg or 1.0 mg twice daily for 24 weeks in patients with keratoconjunctivitis sicca (KCS0
Determine the safety of oral CF101 in this patients population |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Male or female, 18 years of age and over;
2. Have a diagnosis of moderate-to-severe Aqueous-Deficient
Dry Eye (including Sjögren‟s Syndrome dry eye), as
defined by:
Positive corneal fluorescein staining (FS), defined
as a corneal punctate fluorescein staining score of
≥4 in either eye by the National Eye Institute
evaluation scale1, summed over 5 areas each with a
0-3 scoring scale; AND
FS score of ≥2 in at least one corneal region; AND
Schirmer Test (ST) score (without anesthesia) 1 mm
and < 7 mm/5 min in either eye; AND
OSDI score of ≥20;
3. Central corneal FS score of ≥2 in at least 1 eye;
4. Willing to use no topical ocular treatments, other than
Sponsor-supplied artificial tears up to a maximum of 4
times daily, for the duration of the trial (including the 2-
week run-in period, the 24-week treatment period and the
2-week follow-up period);
5. Willing to forego periocular cosmetic application for the
duration of the trial;
6. Females of child-bearing potential must have a negative
urine pregnancy test at screening and throughout the study,
to be eligible for, and continue participation in, the study;
7. Females of child-bearing potential must be willing to use 2
methods of contraception deemed adequate by the
Investigator (for example oral contraceptive pills plus a
barrier method) to be eligible for, and continue
participation in, the study;
8. Dose of oral contraceptive agent, if used, must be stable
for 3 months prior to the Screening Visit and will remain
so during the course of the trial;
9. Ability to complete the study in compliance with the
protocol; and
10. Ability to understand and provide written informed
consent. |
|
| E.4 | Principal exclusion criteria |
1. Sjögren‟s Syndrome with significant systemic nonexocrine
gland involvement which, in the investigator‟s
opinion, would interfere with the conduct of the trial;
2. Stevens-Johnson Syndrome;
3. Use of methotrexate or systemic cyclosporine within the 3
months prior to the Screening Visit;
4. Use of any other disease-modifying anti-rheumatic therapy
within 2 months prior to the Screening Visit;
5. Use of any anti-rheumatic biological agent within 2
months, or 5 half-lives, whichever is longer, prior to the
Screening Visit;
6. Use of oral corticosteroids >10 mg prednisone, or
equivalent, per day;
7. Use of topical steroids within 4 weeks prior to the
Screening Visit and for the duration of the study;
8. Receipt of topical cyclosporine eye drops within 3 months
prior to the Screening Visit and for the duration of the
trial;
9. Use of oral statins, preparations containing omega-3 fatty
acids, chronic antibiotics for the management of
blepharitis, and preparations containing theophylline or
aminophylline unless the dose has been stable for at least 3
months and will remain so during the course of the trial;
10. Presence of chronic ocular disease other than Aqueous-
Deficient Dry Eye requiring topical treatment;
11. Presence of post-burn ocular injury;
12. Ocular herpes simplex virus infection;
13. Graft-versus-host disease;
14. Concomitant use of contact lenses or use within 3 months
prior to the Screening Visit;
15. Persistent intraocular inflammation or infection;
16. Active anterior blepharitis of greater than mild degree,
defined as minimal crust at the base of the eyelashes and
no signs of inflammation;
17. Meibomian gland dysfunction of greater than mild degree,
defined as mild plugging of the Meibomian glands without
lid margin inflammation;
18. Surgical occlusion of the lacrimal puncta, including the
insertion of punctual plugs, within 3 months of the
Screening Visit;
19. Subepithelial corneal scarring;
20. Anesthetic or neurotrophic corneas;
21. Refractive corneal surgery within one year of treatment;
22. History of glaucoma filtering surgery;
23. Serum creatinine level >1.5 times the laboratory‟s normal
limits;
24. Liver aminotransferase levels greater than the laboratory‟s
upper limit of normal;
25. Pregnancy, planned pregnancy, lactation, or inadequate
contraception as judged by the Investigator;
26. Active drug or alcohol dependence;
27. Previous receipt of CF101;
28. Participation in another investigational drug or vaccine
trial concurrently or within 30 days; or
29. Significant acute or chronic medical, ophthalmic, or
psychiatric illness that, in the judgment of the Investigator,
could compromise patient safety, limit the patient‟s ability
to complete the study, and/or compromise the objectives of
the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the proportion of patients who achieve complete clearing of corneal staining (ie, total corneal FS score = 0) at Week 24. The primary efficacy analysis will be performed for one eye (target eye), defined as the eye with the larger corneal FS value at Baseline. If both eyes have the same corneal FS value at baseline, the target eye will be considered the eye with the larger central corneal staining value at Baseline. If both eyes have the same corneal FS value and the same central corneal staining value at Baseline, the left eye will be considered the target eye. The assessment of superficial punctate keratitis using FS will be the sum of scores from central, nasal, temporal, superior, and inferior segments (graded on a scale from 0 = none to 3 = severe).1
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The proportion of the patients who achieve complete clearing of corneal stainig( ie, total corneal fluorescein [FS] at week 24 |
|
| E.5.2 | Secondary end point(s) |
Proportion of patients with complete central corneal clearing (ie, central FS score=0) in the target eye at Week 24; Proportion of patients with Schirmer test(ST) wetting increase over Baseline of ≥10 mm with or whithout anesthesia in either eye at week 24; Change from baseline in Ocular Surface Disease Index (OSDI) at Week 24
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| 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) | 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.8.2.4 | 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 12 |
| 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 |
| Bulgaria |
| Israel |
| Romania |
| United States |
|
| 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 | 1 |
| 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 | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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