Keratoconjunctivitis SiccaPhase 3NCT01235234
Trial of CF101 to Treat Patients With Dry Eye Disease
A Phase 3 study testing CF101 in people with Keratoconjunctivitis Sicca, run by Can-Fite BioPharma at 1 site in Israel.
Trial summary
Eligible patients with dry eye will be treated with CF101 or placebo twice daily for 24 weeks. Disease activity will be assessed using evaluations of ocular surface integrity, tear production, and patient symptoms. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Keratoconjunctivitis Sicca
- What is being tested?
- CF101
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 236 participants
- Where
- 1 siteIsrael
- Study dates
- Jul 2011to Dec 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, 18 years of age and over;
- 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 scale 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;
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- Central corneal FS score of ≥2 in at least 1 eye;
- Willing to use no topical ocular treatments, other than REFRESH® unpreserved 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);
- Willing to forego periocular cosmetic application for the duration of the trial;
- 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;
- 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;
- Ability to complete the study in compliance with the protocol; and
- Ability to understand and provide written informed consent.
Who cannot join
- Sjögren's Syndrome with significant systemic non-exocrine gland involvement which, in the investigator"s opinion, would interfere with the conduct of the trial;
- Stevens-Johnson Syndrome;
- Use of methotrexate or systemic cyclosporine within the 3 months prior to the Screening Visit;
- of any other disease-modifying anti-rheumatic therapy within 2 months prior to the Screening Visit;
- Use of any anti-rheumatic biological agent within 2 months, or 5 half-lives, whichever is longer, prior to the Screening Visit;
- Use of oral corticosteroids >10 mg prednisone, or equivalent, per day;
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- Use of topical steroids within 4 weeks prior to the Screening Visit and for the duration of the study;
- Receipt of topical cyclosporine eye drops within 3 months prior to the Screening Visit and for the duration of the trial;
- Use of oral statin or preparation containing omega-3 fatty acid unless dose has been stable for at least 3 months and will remain so during the course of the trial;
- Presence of chronic ocular disease other than Aqueous-Deficient Dry Eye requiring topical treatment;
- Presence of post-burn ocular injury;
- Ocular herpes simplex virus infection;
- Concomitant use of contact lenses or use within 3 months prior to the Screening Visit;
- Persistent intraocular inflammation or infection;
- Active anterior blepharitis of greater than mild degree, defined as minimal crust at the base of the eyelashes and no signs of inflammation;
- Meibomian gland dysfunction (MGD) of greater than mild degree, defined as mild plugging of the Meibomian glands without lid margin inflammation;
- Surgical occlusion of the lacrimal puncta, including the insertion of punctual plugs, within 3 months of the Screening Visit.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 3, Randomized, Double-Masked, Placebo-Controlled, Dose-Finding, Parallel-Group Study of the Safety and Efficacy of Daily CF101 Administered Orally in Patients With Moderate-to-Severe Dry Eye Disease
Eligible patients with dry eye will be treated with CF101 or placebo twice daily for 24 weeks. Disease activity will be assessed using evaluations of ocular surface integrity, tear production, and patient symptoms.
Read the detailed description
Patients will be randomized to receive either CF101 0.1 mg, CF101 1.0 mg, or matching placebo, given orally twice daily (BID) for 24 weeks. A Screening Period of up to 4 weeks that includes a 2-week run-in period will precede a 24-week treatment period, followed by a 2-week follow-up period.
At a Screening Visit, patients will undergo complete medical and ophthalmologic history, medication history, physical examination (including height, weight, sitting blood pressure, pulse rate and temperature), ophthalmic examination, and clinical laboratory tests. Disease activity will be assessed using fluorescein staining, Schirmer test with and without anesthesia, Ocular Surface Disease Index©, and tear break-up time.
Eligible patients will begin a 2-week run-in period during the 4-week screening period, during which time they will be instructed to discontinue use of all topical ophthalmic medications except for REFRESH TEARS® Lubricant Eye Drops. At the Baseline Visit, patients who successfully complete the 2-week run-in period and re-qualify for entry will be randomized to their assigned medication (CF101 0.1 mg, CF101 1.0 mg, or matching placebo) to be taken orally twice daily BID for 24 weeks. Patients will return for assessments and a new supply of study medication at Weeks 2, 4, 8, 12, 16, and 20; at Week 24 for a final on-treatment assessment; and at Week 26 for the 2-week off-treatment follow-up visit.
- Conditions
- Keratoconjunctivitis Sicca
- Being tested
- CF101
- Keywords
- Dry eye disease, KCS, Aqueous Deficient Dry Eye
- Medical subject headings
- Keratoconjunctivitis Sicca, Dry Eye Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CF101Drug
Also called IB-MECA
orally q12h
| Study group | Role | What they receive |
|---|---|---|
| CF101 0.1 mg | Experimental | Subjects were randomized to receive CF 101 0.1mg, orally, twice daily for 24 weeks Receives: Drug: CF101 |
| CF101 1 mg | Experimental | Subjects were randomized to receive CF 101 1.0mg, orally, twice daily for 24 weeks Receives: Drug: CF101 |
| Placebo | Placebo comparator | Subjects were randomized to receive matching placebo, orally, twice daily for 24 weeks Receives: Drug: CF101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects Who Achieved Complete Clearing of Corneal Staining (i.e., Total Corneal FS Score = 0) at Week 24
Complete clearing of corneal staining by fluorescein staining (FS). The primary efficacy analysis was performed for 1eye (target eye), defined as the eye with the larger corneal FS value at Baseline. If both eyes had the same corneal FS value at baseline, the target eye was considered the eye with the larger central corneal staining value at Baseline. Corneal FS defined as a corneal punctate fluorescein staining score of ≥4 in either eye by the National Eye Institute evaluation scale summed over 5 areas each with a 0-3 scoring scale
Measured: 24 weeks
Number of Subjects With Adverse Events
Determine the safety of oral CF 101 in this subject population. Adverse Events (AEs) and changes in vital signs, physical examination, clinical laboratory tests (liver, kidney, hematology, chemistry and urinalysis), electrocardiogram (ECG) findings, slit lamp and ophthalmic examination, visual acuity, and intraocular pressure measurements.
Measured: 24 weeks
Secondary outcomes (2)
Number of Subjects Who Achieve an Increase in Schirmer Test Tearing by >9mm Over Baseline
ST wetting increase over Baseline of ≥10 mm with or without anesthesia in either eye at Week 24, using a strip of filter paper placed inside the lower eyelid
Measured: 24 weeks
Ocular Surface Disease Index
The Ocular Surface Disease Index is assessed on a scale of 0 to 100, with higher scores representing greater disability.
The subtotal score is based on 12 questions with answers ranging from 0 - "none the time," to 4 - "all of the time."
The number of questions answered is totaled (0 - 12).
The OSDI is calculated using the sum of subtotal scores (0-48) multiplied by 25, divided by number of questions answered (0-12). (i.e., if a participant answers all 12 questions with a severe outcome of 4, their respected OSDI = [(4 x 12) x 25] / 12 = [48 x 25] / 12 = 100)
The outcome measured is the Mean Change from Baseline in Ocular Surface Disease Index at Week 24
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2010 (estimated)
- Study startJul 2011
- Primary completionNov 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Keratoconjunctivitis SiccaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 236 participants (actual)
Sponsor and investigators
- Lead sponsor
- Can-Fite BioPharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael H Silverman, MD, Study director, Can-Fite BioPharma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01235234
- Sponsor's protocol ID
- CF101-301KCS
- Status last verified
- Jun 2022
- First submitted
- 3 Nov 2010
- Last updated
- 30 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Avni I, Garzozi HJ, Barequet IS, Segev F, Varssano D, Sartani G, Chetrit N, Bakshi E, Zadok D, Tomkins O, Litvin G, Jacobson KA, Fishman S, Harpaz Z, Farbstein M, Yehuda SB, Silverman MH, Kerns WD, Bristol DR, Cohn I, Fishman P. Treatment of dry eye syndrome with orally administered CF101: data from a phase 2 clinical trial. Ophthalmology. 2010 Jul;117(7):1287-93. doi: 10.1016/j.ophtha.2009.11.029. Epub 2010 Mar 20.
PubMed 20304499
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-Masked, Placebo-Controlled, Dose-Finding, Parallel-Group Study of the Safety and Efficacy of Daily CF101 Administered Orally in Patients With Moderate-to-Severe Dry Eye Disease
- ClinicalTrials.gov ID
- NCT01235234
- Acronym / sponsor ID
- CF101-301KCS
- Conditions
- Keratoconjunctivitis Sicca
- Keywords
- Dry eye disease, KCS, Aqueous Deficient Dry Eye
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 236 participants (actual)
- Lead sponsor
- Can-Fite BioPharmaIndustry (pharma, biotech, devices)
- Study start
- Jul 2011
- Primary completion
- Nov 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 5 Nov 2010 (estimated)
- Results
- Posted 11 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Eligible patients with dry eye will be treated with CF101 or placebo twice daily for 24 weeks. Disease activity will be assessed using evaluations of ocular surface integrity, tear production, and patient symptoms.
Detailed description
Patients will be randomized to receive either CF101 0.1 mg, CF101 1.0 mg, or matching placebo, given orally twice daily (BID) for 24 weeks. A Screening Period of up to 4 weeks that includes a 2-week run-in period will precede a 24-week treatment period, followed by a 2-week follow-up period.
At a Screening Visit, patients will undergo complete medical and ophthalmologic history, medication history, physical examination (including height, weight, sitting blood pressure, pulse rate and temperature), ophthalmic examination, and clinical laboratory tests. Disease activity will be assessed using fluorescein staining, Schirmer test with and without anesthesia, Ocular Surface Disease Index©, and tear break-up time.
Eligible patients will begin a 2-week run-in period during the 4-week screening period, during which time they will be instructed to discontinue use of all topical ophthalmic medications except for REFRESH TEARS® Lubricant Eye Drops. At the Baseline Visit, patients who successfully complete the 2-week run-in period and re-qualify for entry will be randomized to their assigned medication (CF101 0.1 mg, CF101 1.0 mg, or matching placebo) to be taken orally twice daily BID for 24 weeks. Patients will return for assessments and a new supply of study medication at Weeks 2, 4, 8, 12, 16, and 20; at Week 24 for a final on-treatment assessment; and at Week 26 for the 2-week off-treatment follow-up visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| CF101 0.1 mg | Experimental | Drug: CF101Subjects were randomized to receive CF 101 0.1mg, orally, twice daily for 24 weeks |
| CF101 1 mg | Experimental | Drug: CF101Subjects were randomized to receive CF 101 1.0mg, orally, twice daily for 24 weeks |
| Placebo | Placebo comparator | Drug: CF101Subjects were randomized to receive matching placebo, orally, twice daily for 24 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Male or female, 18 years of age and over;
- Have a diagnosis of moderate-to-severe Aqueous-Deficient Dry Eye (including Sjögren's Syndrome dry eye), as defined by:
- Central corneal FS score of ≥2 in at least 1 eye;
- Willing to use no topical ocular treatments, other than REFRESH® unpreserved 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);
- Willing to forego periocular cosmetic application for the duration of the trial;
Key exclusion criteria (17 listed)
- Sjögren's Syndrome with significant systemic non-exocrine gland involvement which, in the investigator"s opinion, would interfere with the conduct of the trial;
- Stevens-Johnson Syndrome;
- Use of methotrexate or systemic cyclosporine within the 3 months prior to the Screening Visit;
- of any other disease-modifying anti-rheumatic therapy within 2 months prior to the Screening Visit;
- Use of any anti-rheumatic biological agent within 2 months, or 5 half-lives, whichever is longer, prior to the Screening Visit;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CF101Also: IB-MECAorally q12h | Drug | CF101 0.1 mg, CF101 1 mg, Placebo |
Primary outcome
Number of Subjects Who Achieved Complete Clearing of Corneal Staining (i.e., Total Corneal FS Score = 0) at Week 24
Time frame: 24 weeks
Complete clearing of corneal staining by fluorescein staining (FS). The primary efficacy analysis was performed for 1eye (target eye), defined as the eye with the larger corneal FS value at Baseline. If both eyes had the same corneal FS value at baseline, the target eye was considered the eye with the larger central corneal staining value at Baseline. Corneal FS defined as a corneal punctate fluorescein staining score of ≥4 in either eye by the National Eye Institute evaluation scale summed over 5 areas each with a 0-3 scoring scale
Number of Subjects With Adverse Events
Time frame: 24 weeks
Determine the safety of oral CF 101 in this subject population. Adverse Events (AEs) and changes in vital signs, physical examination, clinical laboratory tests (liver, kidney, hematology, chemistry and urinalysis), electrocardiogram (ECG) findings, slit lamp and ophthalmic examination, visual acuity, and intraocular pressure measurements.
2 secondary outcomes
Number of Subjects Who Achieve an Increase in Schirmer Test Tearing by >9mm Over Baseline
Time frame: 24 weeks
Ocular Surface Disease Index
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20304499Avni I, Garzozi HJ, Barequet IS, Segev F, Varssano D, Sartani G, Chetrit N, Bakshi E, Zadok D, Tomkins O, Litvin G, Jacobson KA, Fishman S, Harpaz Z, Farbstein M, Yehuda SB, Silverman MH, Kerns WD, Bristol DR, Cohn I, Fishman P. Treatment of dry eye syndrome with orally administered CF101: data from a phase 2 clinical trial. Ophthalmology. 2010 Jul;117(7):1287-93. doi: 10.1016/j.ophtha.2009.11.029. Epub 2010 Mar 20.
- SponsorLink provided by the sponsor.
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Dry Eye Disease (DED), Keratoconjunctivitis Sicca
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael H Silverman, MD study director
Can-Fite BioPharma
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CF101 in people with Keratoconjunctivitis Sicca, run by Can-Fite BioPharma at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects Who Achieved Complete Clearing of Corneal Staining (i.e., Total Corneal FS Score = 0) at Week 24 (time frame: 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01235234, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2022; AzTrials last refreshed its copy on 8 Nov 2026.