Safety and Efficacy Study of CF101 to Treat Keratoconjunctivitis Sicca

Sponsor
Can-Fite BioPharma (Industry)
Overall Status
Completed
CT.gov ID
NCT00349466
Collaborator
(none)
80
3
2
28
26.7
1

Study Details

Study Description

Brief 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). 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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

Study Type:
Interventional
Actual Enrollment :
80 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Study Start Date :
Jan 1, 2007
Actual Primary Completion Date :
May 1, 2009
Actual Study Completion Date :
May 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: CF101 1mg

CF101 1 mg given orally every 12 hours for 12 weeks

Drug: CF101
Orally CF101 1mg
Other Names:
  • Piclidenoson
  • Placebo Comparator: Placebo

    Placebo given orally every 12 hours for 12 weeks

    Drug: Placebo
    Orally matching Placebo
    Other Names:
  • Inactive pill
  • Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline to Week 12 in Schirmer Test (ST) Score in Millimeters [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.

    2. Change From Baseline to Week 12 in Tear Break-Up Time (BUT) in Seconds [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.

    3. Number of Subjects With >25% Improvement in Fluorescein Staining of the Cornea (FS) at Week 12 [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.

    Secondary Outcome Measures

    1. Number of Subjects Experiencing Clinical Success at Week 12 [12 weeks]

      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)

    2. Change From Baseline to 12 Weeks in Dry Eye Symptom Score (DESS) [12 weeks]

      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.

    3. Change From Baseline to Week 12 in Tear Meniscus (TM) Height [12 weeks]

      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.

    4. Percent Change From Baseline to Week 12 in the Use of Artificial Tears [12 weeks]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • 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.

    Exclusion Criteria:
    • 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;

    • 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Meir Hospital Kfar-Saba Israel 44281
    2 Sheba Medical Center Tel Hashomer Israel 5262
    3 Assaf Harofeh Medical Center Tsrifin Israel 70300

    Sponsors and Collaborators

    • Can-Fite BioPharma

    Investigators

    • Principal Investigator: Irit Bareket, MD, Sheba Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Can-Fite BioPharma
    ClinicalTrials.gov Identifier:
    NCT00349466
    Other Study ID Numbers:
    • CF101-201KCS
    First Posted:
    Jul 7, 2006
    Last Update Posted:
    May 9, 2022
    Last Verified:
    Feb 1, 2022
    Keywords provided by Can-Fite BioPharma
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title CF101 1 mg Placebo
    Arm/Group Description CF101 1 mg q12 hours Placebo tablets q12 hours for 12 weeks
    Period Title: Overall Study
    STARTED 42 38
    COMPLETED 33 35
    NOT COMPLETED 9 3

    Baseline Characteristics

    Arm/Group Title CF101 1 mg Placebo Total
    Arm/Group Description CF101 1 mg q12 hours Placebo tablets q12 hours for 12 weeks Total of all reporting groups
    Overall Participants 42 38 80
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    56.2
    (14.4)
    61.4
    (1311.7)
    58.7
    (13.4)
    Sex: Female, Male (Count of Participants)
    Female
    24
    57.1%
    28
    73.7%
    52
    65%
    Male
    18
    42.9%
    10
    26.3%
    28
    35%
    Region of Enrollment (participants) [Number]
    Israel
    42
    100%
    38
    100%
    80
    100%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline to Week 12 in Schirmer Test (ST) Score in Millimeters
    Description 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.
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    ITT
    Arm/Group Title CF101 1 mg Placebo
    Arm/Group Description Oral tablets given every 12 hours for 12 weeks Oral tablets given every 12 hours for 12 weeks
    Measure Participants 26 23
    Least Squares Mean (Standard Error) [Millimeters]
    1.25
    (0.765)
    3.81
    (0.814)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection CF101 1 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.027
    Comments
    Method ANCOVA
    Comments
    2. Primary Outcome
    Title Change From Baseline to Week 12 in Tear Break-Up Time (BUT) in Seconds
    Description 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.
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    ITT
    Arm/Group Title CF101 1 mg Placebo
    Arm/Group Description Oral tablets given every 12 hours for 12 weeks Oral tablets given every 12 hours for 12 weeks
    Measure Participants 26 23
    Least Squares Mean (Standard Error) [seconds]
    2.83
    (0.906)
    0.48
    (0.083)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection CF101 1 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.083
    Comments
    Method ANCOVA
    Comments
    3. Primary Outcome
    Title Number of Subjects With >25% Improvement in Fluorescein Staining of the Cornea (FS) at Week 12
    Description 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.
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    ITT
    Arm/Group Title CF101 1 mg BID Placebo BID
    Arm/Group Description Oral tablets given every 12 hours for 12 weeks Oral tablets given every 12 hours for 12 weeks
    Measure Participants 26 23
    Number [participants]
    22
    52.4%
    12
    31.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection CF101 1 mg, Placebo
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.028
    Comments
    Method Fisher Exact
    Comments
    4. Secondary Outcome
    Title Number of Subjects Experiencing Clinical Success at Week 12
    Description 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)
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    ITT
    Arm/Group Title CF101 1 mg Placebo
    Arm/Group Description Oral tablets given every 12 hours for 12 weeks Oral tablets given every 12 hours for 12 weeks
    Measure Participants 26 23
    Count of Participants [Participants]
    24
    57.1%
    20
    52.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection CF101 1 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.655
    Comments
    Method Fisher Exact
    Comments
    5. Secondary Outcome
    Title Change From Baseline to 12 Weeks in Dry Eye Symptom Score (DESS)
    Description 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.
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    ITT
    Arm/Group Title CF101 1 mg Placebo
    Arm/Group Description Oral tablets given every 12 hours for 12 weeks Oral tablets given every 12 hours for 12 weeks
    Measure Participants 26 23
    Mean (Standard Deviation) [score on a scale]
    34.44
    (25.393)
    34.53
    (20.605)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection CF101 1 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.387
    Comments
    Method ANCOVA
    Comments
    6. Secondary Outcome
    Title Change From Baseline to Week 12 in Tear Meniscus (TM) Height
    Description 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.
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    ITT
    Arm/Group Title CF101 1 mg Placebo
    Arm/Group Description Oral tablets given every 12 hours for 12 weeks Oral tablets given every 12 hours for 12 weeks
    Measure Participants 26 23
    Mean (Standard Deviation) [units on a scale]
    0.38
    (0.637)
    0.13
    (0.694)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection CF101 1 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.203
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    7. Secondary Outcome
    Title Percent Change From Baseline to Week 12 in the Use of Artificial Tears
    Description 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.
    Time Frame 12 weeks

    Outcome Measure Data

    Analysis Population Description
    ITT
    Arm/Group Title CF101 1 mg Placebo
    Arm/Group Description Oral tablets given every 12 hours for 12 weeks Oral tablets given every 12 hours for 12 weeks
    Measure Participants 26 23
    Least Squares Mean (Standard Error) [percentage change from baseline]
    355625.0
    (410162.00)
    187883.1
    (477720.08)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection CF101 1 mg, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value .807
    Comments
    Method ANCOVA
    Comments

    Adverse Events

    Time Frame Starting on week 2 till week 12 and continue till follow up visit on week 14
    Adverse Event Reporting Description
    Arm/Group Title CF101 1 mg Placebo
    Arm/Group Description CF101 1 mg q12 hours Placebo tablets q12 hours for 12 weeks
    All Cause Mortality
    CF101 1 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    CF101 1 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/39 (0%) 0/37 (0%)
    Other (Not Including Serious) Adverse Events
    CF101 1 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 20/39 (51.3%) 8/37 (21.6%)
    Cardiac disorders
    Palpitations 3/39 (7.7%) 3 0/37 (0%) 0
    Gastrointestinal disorders
    Constipation 3/39 (7.7%) 3 2/37 (5.4%) 2
    Abdominal pain 2/39 (5.1%) 2 0/37 (0%) 0
    General disorders
    Fatigue 2/39 (5.1%) 2 0/37 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/39 (5.1%) 2 1/37 (2.7%) 1
    Myalgia 2/39 (5.1%) 2 0/37 (0%) 0
    Nervous system disorders
    Headache 3/39 (7.7%) 3 4/37 (10.8%) 4
    Skin and subcutaneous tissue disorders
    Itching 3/39 (7.7%) 3 1/37 (2.7%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Pnina Fishman, PhD
    Organization Can-Fite Biopharma
    Phone 011972 3 924 1114
    Email pnina@canfite.co.il
    Responsible Party:
    Can-Fite BioPharma
    ClinicalTrials.gov Identifier:
    NCT00349466
    Other Study ID Numbers:
    • CF101-201KCS
    First Posted:
    Jul 7, 2006
    Last Update Posted:
    May 9, 2022
    Last Verified:
    Feb 1, 2022