Keratoconjunctivitis SiccaPhase 2NCT00349466
Safety and Efficacy Study of CF101 to Treat Keratoconjunctivitis Sicca
A Phase 2 study testing CF101 in people with Keratoconjunctivitis Sicca, run by Can-Fite BioPharma at 3 sites in Israel.
Trial summary
This is a Phase 2, randomized, double-masked, placebo-controlled, parallel-group study in adult males and females, aged 18 years and over, with a diagnosis of moderate-to-severe keratoconjunctivitis sicca (KCS). 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
- 80 participants
- Where
- 3 sitesIsrael
- Study dates
- Jan 2007to May 2009
- Phase
- Phase 2
- 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 KCS as defined by: (1) Schirmer Test (ST) (without anesthesia) < 7 mm/5 min in either eye; AND (2) Positive FS, defined as a corneal punctate fluorescein staining score of ≥1 in either eye, where 0 = none and 3= severe; AND (3) At least 1 of the following ocular symptoms scored at ≥2, where 0 = none and 4 = very severe/interferes with normal activities: photophobia, blurred vision, foreign body sensation, soreness or pain, itching, burning, dryness;
- Willing to use no topical ocular treatments except for the unpreserved artificial tears;
- Doses of unpreserved artificial tears have been stable for >2 weeks prior to Screening Visit;
- 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
- Has Sjögren's Syndrome with significant systemic non-exocrine gland involvement;
- Has Stevens-Johnson Syndrome;
- If KCS is due to rheumatoid arthritis or other autoimmune diseases, patient may not be receiving disease-modifying drugs, including methotrexate and biological agents;
- Use of systemic immunosuppressive drugs;
- Use of oral corticosteroids >10 mg prednisone, or equivalent, per day;
- Use of topical steroids within 2 weeks prior to the Screening Visit and for the duration of the study;
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- Receipt of topical cyclosporine eye drops within 3 months prior to the Screening Visit and for the duration of the trial;
- Presence of chronic ocular disease other than KCS requiring topical treatment;
- Presence of post-burn ocular injury;
- Ocular herpes simplex virus infection;
- Concomitant use of contact lenses;
- Persistent intraocular inflammation or infection;
- Active blepharitis;
- Recent surgical occlusion of the lacrimal puncta;
- Subepithelial corneal scarring;
- Anesthetic or neurotrophic corneas;
- Hemoglobin level <9.0 gm/L;
- Platelet count <125,000/mm^3;
- White blood cell count <3500/mm^3;
- Serum creatinine level outside the laboratory's normal limits;
- Liver aminotransferase levels greater than 2 times the laboratory's upper limit of normal;
- Pregnancy, planned pregnancy, lactation, or inadequate contraception as judged by the Investigator;
- History of malignancy within the past 5 years (excluding basal cell carcinoma of the skin);
- 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;
- Participation in another investigational drug or vaccine trial concurrently or within 30 days; or
- Other conditions which would confound the study evaluations or endanger the safety of the patient.
Trial locations and contacts
3 sites in 1 country.
Israel3 sites
Meir Hospital
Kfar Saba, 44281
Sheba Medical Center
Tel HaShomer, 5262
Assaf Harofeh Medical Center
Tsrifin, 70300
About this study
Official title: A Phase 2, Randomized, Double-Masked, Placebo-Controlled, Parallel-Group Study of the Safety and Efficacy of Daily CF101 Administered Orally in Patients With Moderate-to-Severe Keratoconjunctivitis Sicca
This is a Phase 2, randomized, double-masked, placebo-controlled, parallel-group study in adult males and females, aged 18 years and over, with a diagnosis of moderate-to-severe keratoconjunctivitis sicca (KCS). Patients will be randomized to receive either CF101 1 mg or matching placebo, given orally every 12 hours (q12h) for 12 weeks. A Screening Period of up to 4 weeks that includes a 2-week run-in period will precede a 12-week treatment period, followed by a 2-week follow-up period.
Read the detailed description
At a Screening Visit, patients who provide written informed consent will have screening procedures performed, including a complete medical history, medication history, physical examination, including height, weight, sitting blood pressure, pulse rate and temperature, and clinical laboratory tests. Disease activity will be assessed using tear meniscus (TM) height, tear break-up time (BUT), fluorescein staining (FS), Schirmer test, and the Dry Eye Symptom Score (DESS). Doses of artificial tears must be stable for >2 weeks prior to the Screening Visit.
Eligible patients will begin a 2-week run-in period, during which time they will be instructed to discontinue use of all topical ophthalmic medications except for lubricant eye drops. Patients who successfully complete the 2-week run-in period will be randomized to their assigned medication (CF101 1 mg or matching placebo) to be taken orally every q12h for 12 weeks. Patients will return for assessments and a new supply of study medication at Weeks 2, 4, 8 and 12, and at Week 14 for a final follow-up assessment.
- Conditions
- Keratoconjunctivitis Sicca
- Being tested
- CF101, Placebo
- Keywords
- Keratoconjunctivitis Sicca, KCS, 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 Piclidenoson
Orally CF101 1mg
PlaceboDrug
Also called Inactive pill
Orally matching Placebo
| Study group | Role | What they receive |
|---|---|---|
| CF101 1mg | Experimental | CF101 1 mg given orally every 12 hours for 12 weeks Receives: Drug: CF101 |
| Placebo | Placebo comparator | Placebo given orally every 12 hours for 12 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Week 12 in Schirmer Test (ST) Score in Millimeters
Involved placing a standardized paper tear strip inside the lower eyelid for 5 minutes. The tear strip was then removed and the length of the strip that was wet from tears was measured in millimeters. Change from baseline is calculated. Scores range 0-35 mm, with higher scores indicating more (better) tear production.
Measured: 12 weeks
Change From Baseline to Week 12 in Tear Break-Up Time (BUT) in Seconds
Time elapsed between a complete blink and the development of the first random dry spot on the tear film as seen under fluorescent light. Change from baseline is calculated. Scores range 0-30 seconds, with higher scores indicating better tear composition and function.
Measured: 12 weeks
Number of Subjects With >25% Improvement in Fluorescein Staining of the Cornea (FS) at Week 12
Severity of corneal epithelial loss as graded by Fluorescein Staining of the cornea, assessed on a 0-4+ scale with 0 = none and 4+ = severe de-epithelialization (in other words, higher scores indicate worse disease), expressed as number of participants with >25% improvement at Week 12 relative to baseline.
Measured: 12 weeks
Secondary outcomes (4)
Number of Subjects Experiencing Clinical Success at Week 12
Proportion of subjects experiencing improvement of ≥25% over baseline at Week 12 in (a) tear breakup time (BUT), (b) superficial punctate keratitis as assessed by fluorescein staining (FS), or Schirmer Test (ST)
Measured: 12 weeks
Change From Baseline to 12 Weeks in Dry Eye Symptom Score (DESS)
DESS consists of 12 questions designed to assess the symptoms of ocular irritation, covering three areas: ocular symptoms, environmental triggers and vision-related function. Each of the 12 symptoms can be graded 0-4, with 0 indicating no symptoms over the past week, and 4 meaning constant symptoms over the past week. Scores from all answered questions are summed. The final score is multiplied by (25/number of questions answered) to give an outcome between 0 (no symptoms) to 100 (worst possible symptoms). Change from baseline is calculated.
Measured: 12 weeks
Change From Baseline to Week 12 in Tear Meniscus (TM) Height
Indicator of tear volume. TM was recorded on a scale from 0-3, with 0=none, 1=trace, 2=normal, and 3=high, with higher scores meaning better tear production and integrity. Change from baseline.
Measured: 12 weeks
Percent Change From Baseline to Week 12 in the Use of Artificial Tears
Daily use of REFRESH TEARS® Lubricant Eye Drops artificial tears supplied to each patient was recorded in diaries provided to patients. Percent change from baseline is calculated.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2006 (estimated)
- Study startJan 2007
- Primary completionMay 2009
- Study completionMay 2009
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Can-Fite BioPharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Irit Bareket, MD, Principal investigator, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00349466
- Sponsor's protocol ID
- CF101-201KCS
- Status last verified
- Feb 2022
- First submitted
- 6 Jul 2006
- Last updated
- 9 May 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 9 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-Masked, Placebo-Controlled, Parallel-Group Study of the Safety and Efficacy of Daily CF101 Administered Orally in Patients With Moderate-to-Severe Keratoconjunctivitis Sicca
- ClinicalTrials.gov ID
- NCT00349466
- Acronym / sponsor ID
- CF101-201KCS
- Conditions
- Keratoconjunctivitis Sicca
- Keywords
- Keratoconjunctivitis Sicca, KCS, Dry Eye
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Can-Fite BioPharmaIndustry (pharma, biotech, devices)
- Study start
- Jan 2007
- Primary completion
- May 2009 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 7 Jul 2006 (estimated)
- Results
- Posted 12 Aug 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2, randomized, double-masked, placebo-controlled, parallel-group study in adult males and females, aged 18 years and over, with a diagnosis of moderate-to-severe keratoconjunctivitis sicca (KCS). Patients will be randomized to receive either CF101 1 mg or matching placebo, given orally every 12 hours (q12h) for 12 weeks. A Screening Period of up to 4 weeks that includes a 2-week run-in period will precede a 12-week treatment period, followed by a 2-week follow-up period.
Detailed description
At a Screening Visit, patients who provide written informed consent will have screening procedures performed, including a complete medical history, medication history, physical examination, including height, weight, sitting blood pressure, pulse rate and temperature, and clinical laboratory tests. Disease activity will be assessed using tear meniscus (TM) height, tear break-up time (BUT), fluorescein staining (FS), Schirmer test, and the Dry Eye Symptom Score (DESS). Doses of artificial tears must be stable for >2 weeks prior to the Screening Visit.
Eligible patients will begin a 2-week run-in period, during which time they will be instructed to discontinue use of all topical ophthalmic medications except for lubricant eye drops. Patients who successfully complete the 2-week run-in period will be randomized to their assigned medication (CF101 1 mg or matching placebo) to be taken orally every q12h for 12 weeks. Patients will return for assessments and a new supply of study medication at Weeks 2, 4, 8 and 12, and at Week 14 for a final follow-up assessment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CF101 1mg | Experimental | Drug: CF101CF101 1 mg given orally every 12 hours for 12 weeks |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo given orally every 12 hours for 12 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female, 18 years of age and over;
- Have a diagnosis of moderate-to-severe KCS as defined by: (1) Schirmer Test (ST) (without anesthesia) < 7 mm/5 min in either eye; AND (2) Positive FS, defined as a corneal punctate fluorescein staining score of ≥1 in either eye, where 0 = none and 3= severe; AND (3) At least 1 of the following ocular symptoms scored at ≥2, where 0 = none and 4 = very severe/interferes with normal activities: photophobia, blurred vision, foreign body sensation, soreness or pain, itching, burning, dryness;
- Willing to use no topical ocular treatments except for the unpreserved artificial tears;
- Doses of unpreserved artificial tears have been stable for >2 weeks prior to Screening Visit;
- 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;
Key exclusion criteria (26 listed)
- Has Sjögren's Syndrome with significant systemic non-exocrine gland involvement;
- Has Stevens-Johnson Syndrome;
- If KCS is due to rheumatoid arthritis or other autoimmune diseases, patient may not be receiving disease-modifying drugs, including methotrexate and biological agents;
- Use of systemic immunosuppressive drugs;
- Use of oral corticosteroids >10 mg prednisone, or equivalent, per day;
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: PiclidenosonOrally CF101 1mg | Drug | CF101 1mg |
| PlaceboAlso: Inactive pillOrally matching Placebo | Drug | Placebo |
Primary outcome
Change From Baseline to Week 12 in Schirmer Test (ST) Score in Millimeters
Time frame: 12 weeks
Involved placing a standardized paper tear strip inside the lower eyelid for 5 minutes. The tear strip was then removed and the length of the strip that was wet from tears was measured in millimeters. Change from baseline is calculated. Scores range 0-35 mm, with higher scores indicating more (better) tear production.
Change From Baseline to Week 12 in Tear Break-Up Time (BUT) in Seconds
Time frame: 12 weeks
Time elapsed between a complete blink and the development of the first random dry spot on the tear film as seen under fluorescent light. Change from baseline is calculated. Scores range 0-30 seconds, with higher scores indicating better tear composition and function.
Number of Subjects With >25% Improvement in Fluorescein Staining of the Cornea (FS) at Week 12
Time frame: 12 weeks
Severity of corneal epithelial loss as graded by Fluorescein Staining of the cornea, assessed on a 0-4+ scale with 0 = none and 4+ = severe de-epithelialization (in other words, higher scores indicate worse disease), expressed as number of participants with >25% improvement at Week 12 relative to baseline.
4 secondary outcomes
Number of Subjects Experiencing Clinical Success at Week 12
Time frame: 12 weeks
Change From Baseline to 12 Weeks in Dry Eye Symptom Score (DESS)
Time frame: 12 weeks
Change From Baseline to Week 12 in Tear Meniscus (TM) Height
Time frame: 12 weeks
Percent Change From Baseline to Week 12 in the Use of Artificial Tears
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: 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.
- Can-Fite BioPharma web siteLink provided by the sponsor.
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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.
Irit Bareket, MD principal investigator
Sheba Medical Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CF101 in people with Keratoconjunctivitis Sicca, run by Can-Fite BioPharma at 3 sites 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 8 inclusion and 26 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 9 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 12 Aug 2011). 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?
Change From Baseline to Week 12 in Schirmer Test (ST) Score in Millimeters (time frame: 12 weeks). The study lists 3 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 NCT00349466, 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 9 May 2022.