24-hour Efficacy and Tolerability of the Tafluprost-timolol Fixed Association Without Preservatives in Glaucomatous or Ocular Hypertensive Patients Already Treated With Latanoprost Preserved With BAK. A Prospective, Open Study of 3 Months Duration. (HERO)

This is a phase IV, interventional, multi-center, open clinical Trial. Patients will be administered one eye drop of tafluprost/timolol fixed combination at 20:00 (+/- 1 hour), in the treatment of open angle glaucoma and ocular hypertension. The patients will suspend the treatment with latanoprost.

Study Overview

• Status: Recruiting
• Conditions: Ocular Hypertension; Glaucoma, Open-Angle
• Intervention / Treatment: Drug: tafluprost/timolol

Detailed Description

This is a phase IV, interventional, multi-center, not comparative, open clinical Trial to evaluate the effectiveness in reducing the mean 24-hour IOP of the preservative-free fixed combination of Tafluprost 0.0015% and Timolol 0.5% administered once at night (8pm) in POAG or OHT patients suffering from mild OSD and requiring further IOP reduction while in topical treatment with BAK-preserved Latanoprost 0.05 mg/ml. Three Italian recruiting centers are included in the study and the estimated number of patients to be enrolled is 43. After evaluating the patient's eligibility, the patients will suspend the treatment with latanoprost and will be administered one eye drop of tafluprost/timolol fixed combination at 20:00 (+/- 1 hour) at the end of the V1B visit. Active drug will be contained (about 30 µl, one drop) contains about 0.45 micrograms of tafluprost and 0.15 mg of timolol.

The Study consists in 6 Visits:

1. Screening visit V0 and baseline V1A.
2. Treatment period visit V1B; V2; V3A; V3B.
3. End of study V3B.

• Study Type: Interventional
• Enrollment (Anticipated): 43
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Francesco Oddone, MD; Phone Number: 0039 0685356727; Email: francesco.oddone@fondazionebietti.it
• Study Contact Backup: Name: Lucia Tanga, MD; Phone Number: 0039 3381177456; Email: lucia.tanga@fondazionebietti.it

Study Locations

• Italy
  • Milano, Italy, 20142
    • Recruiting
    • ASST Santi Paolo e Carlo
    • Contact: Alfonso Strianese, MD; Phone Number: 0039 3347302078; Email: alfonsostrianese95@gmail.com
  • Pavia, Italy, 27100
    • Not yet recruiting
    • Università di Pavia Policlinico S. Matteo
    • Contact: Ivano Riva, MD; Phone Number: 0039 3471630745; Email: ivano.riva@virgilio.it
  • Roma, Italy, 00198
    • Recruiting
    • IRCCS G.B.Bietti Foundation for the study and Research in Ophthalmology ONLUS
    • Contact: Lucia Tanga, MD; Phone Number: 0039 3381177456; Email: lucia.tanga@fondazionebietti.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ocular hypertension or primary open-angle glaucoma or secondary to dispersion of pigment or pseudoesfoliatio;
2. IOP <22 mmHg in latanoprost therapy in both eyes since at least 6 weeks and > 17 mmHg in at least one eye;
3. OSD at least mild as defined by DEQ-5 (score> 6);
4. Examination of the visual field during the three months prior to enrollment (if not present, the patient must be subjected to a visual field at the screening visit);
5. Treatment with latanoprost BAK-preserved from at least 6 weeks;
6. Subject agrees to follow the study procedures and signs the EC-approved ICF;
7. For women of child-bearing potential, blood screening for beta-HCG before randomization and use of one effective method of birth control during the conduct of the study

Exclusion Criteria:

1. Inability to understand and sign informed consent;
2. Age under 18 years;
3. Other forms of secondary glaucoma (besides pigmentary and pseudoesfoliatius);
4. Narrow angle or history of acute glaucoma attacks;
5. Previous history of trabeculoplasty in the previous 6 months;
6. History of glaucoma surgery or refractive surgery;
7. Cataract surgery in the 6 months prior to enrollment;
8. Contraindications to the use of beta-blockers (reactive airway disease, including bronchial asthma or a history of bronchial asthma, severe chronic obstructive pulmonary disease; sinus bradycardia, sick sinus syndrome, including sinoatrial block, second or third degree atrioventricular block not controlled by pacemaker; full-blown heart failure, cardiogenic shock);
9. Damage to the visual field with a mean deviation (MD) <-20 dB;
10. BCVA <2/10;
11. Topical ocular drugs performed within 3 months prior to enrollment that may interfere with the study results (eg steroids, non-steroidal anti-inflammatory drugs, immunosuppressants, etc.);
12. Use of tear substitutes containing preservatives within 30 days prior to enrollment;
13. Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful completion of the study or would impair interpretation of results;
14. Corneal anomalies that preclude an accurate measurement of IOP (eg astigmatism> 3 D, keratoconus, opacity or corneal ulcers);
15. Any type of previous corneal or conjunctival surgery including pterygium removal or refractive surgery;
16. Unstable systemic disorders that may require the initiation or variation of therapies that may influence intraocular pressure during the study;
17. Woman of childbearing potential, or who is currently pregnant or breastfeeding;
18. Inability to adhere to the procedures required by the protocol or to the studio treatment;
19. Participation in another experimental therapeutic protocol within one month prior to baseline and during the study period (participation in natural history study is allowed);
20. Hypersensitivity to the active substances or to any of the excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: tafluprost/timolol; Enrolled patients will be treated with one drop of the fixed combination Tafluprost-Thymol without preservative in the evening at 20.00 (+/- 1 hour). Patients will be administrered with one drop in the conjunctival sac of the affected eye (s) once a day.

Drug: tafluprost/timolol; One ml active drug contains: 15 micrograms of tafluprost and 5 mg of timolol (as maleate). A single-dose container (0.3 ml) of eye drops, solution, contains 4.5 micrograms of tafluprost and 1.5 mg of timolol. One drop (about 30 µl) contains about 0.45 micrograms of tafluprost and 0.15 mg of timolol. Patients will be administrered with one drop in the conjunctival sac of the affected eye (s) once a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The evaluation of the mean 24-h absolute Intraocular Pressure (IOP)	Reduction measured in mmHg (millimeters of mercury).	through study completion, an average of 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the average reduction of Intraocular Pressure(IOP) at 24-hour	Curve measured in mmHg.	through study completion, an average of 3 months
Evaluation of the percentage reduction of the average Intraocular Pressure(IOP) of the 24 hours	percentage at each time point.	through study completion, an average of 3 months
Evaluation of the average daytime reduction and night of the Intraocular Pressure(IOP)	Measured in mmHg	through study completion, an average of 3 months
Evaluation of the percentage of patients achieving Intraocular Pressure(IOP) reduction in average	reductions in average IOP at 24h when plus 20%, when plus 25%,when plus 30%.	through study completion, an average of 3 months
Evaluation of the changes in the Corneale Staining Test (CFS) and Break-up Time Test (tBUT) parameters	with fluorescein, measured area and density	through study completion, an average of 3 months
Evaluation of the changes in Dry Eye Questionnaire (DEQ-5)	DEQ-5 questionnaire Score	through study completion, an average of 3 months
Evaluation of the changes of the number, activation of corneal, conjunctival dendritic cells to confocal microscopy.	Changes number corneal and dendritic cells	through study completion, an average of 3 months
Evaluation of the changes of the number of conjunctival goblet cells to confocal microscopy	Changes of number of goblet cells	through study completion, an average of 3 months
Evaluation of the changes in quality of life	NEIVFQ-25 questionnaire (score).	through study completion, an average of 3 months

Collaborators and Investigators

• Sponsor: Fondazione G.B. Bietti, IRCCS
• Investigators: Principal Investigator: Francesco Oddone, MD, IRCCS G.B.Bietti Foundation for the study and Research in Ophthalmology ONLUS; Principal Investigator: Luciano Quaranta, MD, Università di Pavia Policlinico S. Matteo; Principal Investigator: Luca Rossetti, MD, ASST Santi Paolo e Carlo

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2020
• Primary Completion (Anticipated): June 30, 2022
• Study Completion (Anticipated): June 30, 2022

Study Registration Dates

• First Submitted: February 15, 2022
• First Submitted That Met QC Criteria: March 18, 2022
• First Posted (Actual): March 29, 2022

Study Record Updates

• Last Update Posted (Actual): March 29, 2022
• Last Update Submitted That Met QC Criteria: March 18, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Glaucoma, ocular hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Timolol
• Other Study ID Numbers: HERO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is not a Plan to make available to other researches.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No