Clinical trial NCT03284853: Safety and Efficacy Study of PG324 (Netarsudil/Latanoprost 0.02% / 0.005%) Ophthalmic Solution Compared to GANFORT® Ophthalmic Solution in Open Angle Glaucoma or Ocular Hypertension
Official title: A Prospective, Double-masked, Randomized, Multicenter, Active-controlled, Parallel-group, 6-month Study Assessing the Safety and Ocular Hypotensive Efficacy of PG324 Ophthalmic Solution Compared to GANFORT® (Bimatoprost 0.03% / Timolol 0.5%) Ophthalmic Solution in Subjects With Elevated Intraocular Pressure (MERCURY 3)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Open Angle Glaucoma
Ocular Hypertension
Lead sponsor: Aerie Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-09-15
Enrollment: 436
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is intended to test the effectiveness and safety of Netarsudil / Latanoprost 0.02% / 0.005% Ophthalmic Solution, relative to GANFORT® for lowering of intraocular pressure (IOP) in patients with elevated intraocular pressure


Eligibility criteria: Inclusion Criteria:

1. Must be 18 years of age or older.
2. Diagnosis of OAG or OHT in both eyes (OAG in one eye and OHT in the fellow eye is acceptable).
3. Subjects insufficiently controlled and/or subjects considered in need for combination therapy by the investigators.
4. Medicated intraocular pressure ≥ 17 mmHg in at least one eye and \< 28mmHg in both eyes at screening visit.
5. Unmedicated (post-washout) IOP \>20mmHg in at least one eye and \< 36mmHg in both eyes at 2 qualification visits at 08:00 hour, 2-7 days apart. At the second qualification visit, have IOP \>17mmHg in at least one eye and \< 36mmHg in both eyes at 10:00 and 16:00 hours. Note: For purposes of determining eligibility of subjects to be enrolled, the non-integral IOP mean number will be used. Any non-integral mean IOP number should not be rounded. If only one eye qualifies at the second qualification visit it MUST be the same eye that qualified on the first visit and this will be the study eye for the duration of the study.
6. Best corrected visual acuity +1.0 logMAR or better by ETDRS in each eye (equivalent to 20/200 or better Snellen visual acuity in each eye).
7. Be able and willing to give signed informed consent and follow study instruction.
8. Women must be either of non-childbearing potential, or women with childbearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study.
9. Women of childbearing potential must have a negative urine pregnancy test within 7 days of first dose of study treatment and agree to use highly effective contraception during the study and for 3 months after the last dose of study medication.
10. Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use an effective form of contraception from time of randomization and for 3 months following the last dose of study medication.
11. In France, a subject will be eligible for inclusion in this study only if either affiliated to or as a beneficiary of a social security number.

Exclusion Criteria:

Ophthalmic:

1. Clinically significant ocular disease (e.g., corneal edema, uveitis, or severe keratoconjunctivitis sicca) which might interfere with interpretation of the study efficacy endpoints or with safety assessments, including subjects with glaucomatous damage so severe that washout of ocular hypotensive medications for 4 weeks or longer if needed is not judged safe as it would put the subject at risk for further vision loss.
2. Pseudoexfoliation or pigment dispersion component glaucoma, history of angle closure glaucoma, or narrow angles i.e. Grade 2 Shaffer (Chan 1981) or less extreme narrow angle with complete or partial closure. Note: Previous laser peripheral iridotomy is NOT acceptable.
3. Intraocular pressure ≥ 36mmHg (unmedicated) in either eye (individuals who are excluded for this criterion are not allowed to attempt requalification), or use of more than two ocular hypotensive medications within 30 days of screening. Note: fixed dose combination medications, for the purpose of this exclusion criterion, count as one medication. However, subjects currently taking 2 fixed dose combination products are excluded.
4. Treatment-naïve subjects.
5. Prior treatment with GANFORT® topical eye drops where the subjects IOP did not achieve the target IOP and was considered either a therapeutic failure or to have insufficient response. Subjects currently (immediately prior to screening visit) being treated with GANFORT® are excluded from the study.
6. Known hypersensitivity to any component of the investigational formulations to be used (e.g., benzalkonium chloride) or to fluorescein.
7. Previous glaucoma intraocular surgery, including SLT or ALT in either eye.
8. Refractive surgery in either eye (e.g., radial keratotomy, PRK, LASIK, corneal cross-linking, keratoplasty).
9. Ocular trauma within the six months prior to screening, or ocular surgery or non-refractive laser treatment within the three months prior to screening.
10. Recent or current evidence of ocular infection or inflammation in either eye. Current evidence of clinically significant blepharitis, conjunctivitis, keratitis, current evidence or history of herpes simplex or zoster keratitis in either eye at screening.
11. Use of ocular medication in either eye of any kind within 30 days of screening and throughout the study, with the exception of a) ocular hypotensive medications which must have been the same medication for 30 days prior to screening (which must be washed out according to the provided schedule), b) lid scrubs (which may be used prior to, but not after, screening), c) lubricating drops for dry eye (which may be used throughout the study), as prescribed by the Investigator.
12. Mean central corneal thickness greater than 620μm at screening.
13. Any abnormality preventing reliable Goldmann applanation tonometry of either eye (e.g., keratoconus).

    Systemic:
14. Clinically significant abnormalities in laboratory tests at screening.
15. Known hypersensitivity or contraindication to GANFORT® (Appendix 3 Marketed Product Medication Information Section 4.3) and to β-adrenoceptor antagonists (e.g. Chronic obstructive pulmonary disease or bronchial asthma; abnormally low blood pressure or heart rate; second or third-degree heart block or congestive heart failure, cardiac failure, cardiac shock and severe diabetes).
16. Clinically significant systemic disease which might interfere with the study.
17. Participation in any investigational study within 30 days prior to screening.
18. Systemic medication including corticosteroid containing drugs that could have a substantial effect on IOP which HAVE NOT been maintained at a consistent dose and regime within 30 days prior to screening, and are anticipated to change in dose and/or regime during the study.
19. Use of topical steroid containing medications on the face or in or around the eyes will exclude the subject (see Section 5.6 Concomitant Medications).
20. Women of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable and highly effective form of birth control. An adult woman is considered to be of childbearing potential unless she is one year post-menopausal (1 year without menses with appropriate clinical profile, e.g. age appropriate, \> 45 years in the absence of HRT. In questionable cases the subject must have FSH value \> 40mIU/mL and an estradiol value \< 40pg/mL (\< 140pmol/L)) or three months post-surgical sterilization.
21. Vulnerable subjects such as minors, adults under legal protection or unable to express their consent (e.g. hospitalized persons in coma), persons deprived of liberty (prisoners from jails), or persons subject to psychiatric care.

Primary outcomes:
measure: Mean Diurnal Intraocular Pressure by Goldmann Applanation Tonometry
timeFrame: Day 90
Secondary outcomes:
Other outcomes:
Locations:
city: Graz
country: Austria
facility: State Hospital - University Medical Center Academical Department of Ophthalmology
city: Vienna
country: Austria
facility: Albertgasse 39/10+11
city: Vienna
country: Austria
facility: Hanusch Hospital
city: Leuven
country: Belgium
facility: UZ Leuven, campus Gasthuisberg, Herestraat 49, 3000 Leuven
city: Brno
country: Czechia
facility: Faculty Hospital Brno Eye Department
city: Praha
country: Czechia
facility: Glaucoma center Oční klinika VFN a 1. LF UK
city: Bordeaux
country: France
facility: Ophthalmology Service Centre Francois Xavier Michelet CHU Pellegrin
city: Ecully
country: France
facility: Centre ophtalmologique Pole vision val d'ouest
city: Lyon
country: France
facility: Ophthalmology Service - Batiment R Hospital de la Croix-Rousse
city: Nantes
country: France
facility: CHU de Nantes-Hospital Hotel Dieu Ophthalmology Service
city: Paris
country: France
facility: Ophthalmology department Necker University Hospital-Enfants Malades
city: Freiburg
country: Germany
facility: University Medical Center Freiburg, Eye Center,Killianstr.5, Freiburg i. Breisgau
city: Mainz
country: Germany
facility: Department of Ophthalmology Clinical Johannes Gutenberg-University Mainz
city: Münster
country: Germany
facility: Universitats-Augenklinik, Studienzentrum/Clinical Trials in Opthalmology (CTO)
city: Tuebingen
country: Germany
facility: University Eye Hospital Tuebingen, STC eyetrial at the center for Ophthalmolgy
city: Weilheim
country: Germany
facility: Augenarztpraxis Dr. Andreas Bayer
city: Budapest
country: Hungary
facility: Budapest Retina Associates
city: Budapest
country: Hungary
facility: Department of Ophthalmology Semmelweis University
city: Debrecen
country: Hungary
facility: University of Debrecen, Clinical Center, Ophthalmology Department
city: Heves
country: Hungary
facility: Clinexpert Gyongyos Kft.
city: Pécs
country: Hungary
facility: Ganglion Medical Center
city: Szeged
country: Hungary
facility: University of Szeged, Department of Ophthalmology
city: Szombathely
country: Hungary
facility: Markusovszky University Teaching Hospital
city: Genova
country: Italy
facility: Ophthalmic Clinic DiNOGMI University Hospital San Martino
city: Milano
country: Italy
facility: Dept. Ophthalmology, San Raffaele Hospital
city: Milan
country: Italy
facility: ASST Fatebenefratelli Sacco P.O.L.Sacco
city: Milan
country: Italy
facility: ASST Santi Paolo e Carlo - Ophthalmic Clinic
city: Parma
country: Italy
facility: Department of Medicine and Surgery University of Parma
city: Pavia
country: Italy
facility: Ophthamic Clinic of the University of Pavia, IRCCS Foundation San Matteo Policlinic
city: Pisa
country: Italy
facility: AOU Pisana Hospital of Cisanello
city: Rome
country: Italy
facility: G.B.Bietti Foundation - IRCCS
city: Siena
country: Italy
facility: Senese University Hospital
city: Torino
country: Italy
facility: S.C.U Oculistica, Azienda Ospedaliero Universitaria, Città della Salute e della Scienza
city: Trieste
country: Italy
facility: University Eye Clinic Ospedale Maggiore
city: Verona
country: Italy
facility: Politecnico Gianbattista Rossi AOUI Ospedale Borgo Roma
city: Jelgava
country: Latvia
facility: Signes Ozolinas Doctor Practice in Ophthalmology
city: Riga
country: Latvia
facility: Latvian American Eye Centre (LAAC)
city: Riga
country: Latvia
facility: P.Stradins Clinical University Hospital, Ophthalmology Clinic
city: Riga
country: Latvia
facility: Riga East University hospital, In-patient Department "Biķernieki", Ophthalmology Clinic
city: Katowice
country: Poland
facility: Professor K. Gibinski University Clinical Centre
city: Lublin
country: Poland
facility: Department of Diagnostics and Microsurgery of Glaucoma
city: Warsaw
country: Poland
facility: Military Institute of Medicine Klinika Okulistyki
city: Łódź
country: Poland
facility: Ophthalmic Clinic Jasne Blonia
city: Barcelona
country: Spain
facility: Centro de Oftalmologia Barraquer
city: Barcelona
country: Spain
facility: Hospital General de Catalunya Ophthalmology Department
city: Barcelona
country: Spain
facility: Hospital QuironSalud Barcelona
city: Barcelona
country: Spain
facility: Institut Catala de retina (ICR) Glaucoma and Investigation Department
city: Cádiz
country: Spain
facility: Hospital General del S.A.S. de Jerez de la Frontera
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía de Córdoba
city: La Coruña
country: Spain
facility: Centro de Ojos de la Coruña
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena Ophthalmology Department
city: Torrevieja
country: Spain
facility: Hospital Universitario de Torrevieja Ophthalmology Department
city: Valencia
country: Spain
facility: FISABIO-Oftalmología Médica
city: Valladolid
country: Spain
facility: Ophthalmology Department Hospital Universitario Rio Hortega
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa Zaragoza Ophthalmology department
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet Ophthalmology Department
city: Sunderland
country: United Kingdom
facility: City Hospitals Sunderland NHS Foundation Trust Sunderland Eye Infirmary
state: Tyne And Wear
city: Aberdeen
country: United Kingdom
facility: NHS Grampian Aberdeen Royal Infirmary
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Trust
city: Cosham
country: United Kingdom
facility: Ophthalmology Department, Queen Alexandra Hospital
city: Crewe
country: United Kingdom
facility: Mid-Cheshire Hospitals NHS Foundation Trust
city: Huntingdon
country: United Kingdom
facility: Northwest Anglia NHS Foundation trust Hinchingbrooke Hospital
city: London
country: United Kingdom
facility: Guy's & St Thomas' NHS Foundation Trust Glaucoma Research Area
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Moorfields Eye Hospital NHS
city: London
country: United Kingdom
facility: Western Eye Hospital
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
city: Sidcup
country: United Kingdom
facility: Queen Mary Hospital, King's College Hospital NHS
Study officials:
affiliation: Aerie Pharmaceuticals Inc.
name: Michelle Senchyna
role: STUDY_DIRECTOR
References: