Safety and Efficacy of Daily CF101 Administered Orally in Subjects With Elevated Intraocular Pressure
Condition: Ocular Hypertension; Glaucoma
MeSH terms: Glaucoma; Ocular Hypertension; Hypertension
Intervention: CF101; Placebo for
Intervention description: CF101 1 or 2 mg tablets orally every 12 hours for 16 weeks; Matching placebo tablets orally every 12 hours for 16 weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 89.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Glaucoma; Ocular hypertension; Intraocular hypertension

Summary:

      This study will test the hypothesis that CF101, administered orally, will reduce intraocular
      pressure in patients with ocular hypertension and/or glaucoma. Eligible patients with
      elevated intraocular pressure will be evaluated and treated by ophthalmologist investigators,
      and will receive either CF101 pills or placebo (dummy) pills twice daily for 16 weeks. Ocular
      pressure, visual fields, and other aspects of safety and effectiveness will be monitored on a
      regular basis.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female, 18 years of age and over;

          2. Ocular hypertension or open-angle glaucoma in at least 1 eye, diagnosed as any of the
             following:

               1. Untreated ocular hypertension without glaucomatous anatomic or VF changes; or

               2. Glaucoma diagnosed within the past 2 months but untreated;

               3. Previously treated glaucoma, provided that previous medication treatment has been
                  inefficacious and/or intolerable, and has therefore been discontinued at least 3
                  weeks prior to Baseline; or

               4. Currently treated glaucoma with inadequate IOP control, meaning that IOP remains
                  above target pressure as judged by the Investigator despite ≥3 weeks of treatment
                  with a standard topical regimen (for guidance, the European Glaucoma Society
                  defines "target pressure" as follows: "In most cases a peak IOP = 8 mm - 15 mmHg
                  on a diurnal curve, or 30% IOP reduction from baseline");

          3. In subjects receiving a standard topical treatment regimen (per 2.d. above), the
             regimen and dose have not changed within 3 weeks of Screening, and are expected to
             remain stable throughout the treatment period;

          4. At both Screening and Baseline, IOP in at least 1 eye ("candidate" eye) is >21 mmHg at
             0800-1000 hours and >21 mmHg in at least 1 measurement at least 3 hours following the
             first;

          5. Corneal thickness between 500 and 580 microns in both eyes;

          6. Corrected visual acuity +0.18 logMAR or better by Early Treatment Diabetic Retinopathy
             Study (ETDRS) methodology in the candidate eye (equivalent to 20/30);

          7. 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;

          8. Females of child-bearing potential must be willing to use 2 methods of contraception
             deemed adequate by the Investigator (eg, oral contraceptive pills plus a barrier
             method) to be eligible for, and continue participation in, the study;

          9. Ability to complete the study in compliance with the protocol; and

         10. Ability to understand and provide written informed consent.

        Exclusion Criteria:

          1. IOP >32 mmHg in either eye;

          2. History of angle-closure glaucoma;

          3. Anatomically narrow angles in either eye (ie, ≥75% of the circumference of the angle
             must be ≥Grade 2 by Shaffer criteria );

          4. In subjects with glaucoma, advanced VF defect in either eye, determined on reliable
             testing using the Humphrey Full-Threshold Algorithm for the Glaucoma Hemifield Test,
             defined as either:

               1. Mean deviation worse than -16 dB, or

               2. Threat to fixation (sensitivity 10 dB or worse affecting either or both test
                  points closest to the point of fixation in the upper hemifield and at either or
                  both the corresponding test points in the lower hemifield);

          5. In subjects with ocular hypertension, a score of >12 points on The Ocular Hypertension
             Treatment Study Group and European Glaucoma Prevention Study Group Primary Open-Angle
             Glaucoma Risk Table;

          6. Documented disc hemorrhage within the past 5 years in either eye;

          7. Secondary cause of IOP elevation;

          8. Glaucoma laser treatment in candidate eye within the past 3 months;

          9. Clinically significant ocular trauma to candidate eye within the past 6 months;

         10. Any major ocular surgery in the past, including keratorefractive surgery, in candidate
             eye, except for uncomplicated cataract surgery performed greater than 6 months prior
             to Screening;

         11. Astigmatism >3 diopters in either eye;

         12. Clinically significant acute or chronic ocular disease (eg, corneal edema, uveitis,
             severe keratoconjunctivitis sicca, active ocular infection, active herpes simplex
             keratitis, blepharitis, or acute conjunctivitis) that might interfere with the study;

         13. Concomitant contact lens use;

         14. Concomitant use of systemic medication that may affect IOP (eg, beta blockers,
             corticosteroids, calcium channel blockers, ACE inhibitors, or carbonic anhydrase
             inhibitors); however, systemic antihypertensive medications are allowed providing that
             the dose and regimen have been stable for at least 3 months prior to Screening and are
             expected to remain stable throughout the trial;

         15. Any abnormality preventing reliable applanation tonometry;

         16. Presence of uncontrolled asthma;

         17. Presence of uncontrolled arterial hypertension or symptomatic hypotension;

         18. Significant cardiac arrhythmia or conduction block, congestive heart failure (New York
             Heart Association Class 3-4), or any other evidence of clinically significant heart
             disease or clinically significant findings on screening ECG;

         19. Hemoglobin level <9.0 gm/L, at screening;

         20. Platelet count <125,000/mm3, at screening;

         21. White blood cell count <3500/mm3, at screening;

         22. Serum creatinine level greater than 1.5 times the laboratory's upper limit of normal
             (ULN), at screening;

         23. Liver aminotransferase levels greater than 2 times the laboratory's ULN, at screening;

         24. Known or suspected immunodeficiency or human immunodeficiency virus positivity;

         25. Known infection with hepatitis B or C;

         26. Pregnancy, planned pregnancy, lactation, or inadequate contraception as judged by the
             Investigator;

         27. Previous receipt of CF101;

         28. History of malignancy within the past 5 years (excluding basal cell carcinoma of the
             skin and ≤3 cutaneous squamous cell carcinomas, all of which have been completely
             excised);

         29. Active drug or alcohol dependence;

         30. Significant acute or chronic medical, ophthalmic, neurologic, or psychiatric illness
             that, in the judgment of the Investigator, could compromise subject safety, limit the
             subject's ability to complete the study, and/or compromise the objectives of the
             study;

         31. Participation in another investigational drug or vaccine trial concurrently or within
             30 days; or

         32. Other conditions which would confound the study evaluations or endanger the safety of
             the subject.