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

Ocular Hypertension Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03284853
• Other study ID #: PG324-CS303
• Status: Completed
• Phase: Phase 3
• Start date: September 5, 2017
• Est. completion date: November 6, 2020

Study information

• Verified date: January 2022
• Source: Aerie Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 436
• Est. completion date: November 6, 2020
• Est. primary completion date: November 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Glaucoma
• Glaucoma, Open-Angle
• Hypertension
• Ocular Hypertension
• Open Angle Glaucoma

Intervention

Drug:
• Netarsudil/Latanoprost 0.02%/0.005%
Topical sterile ophthalmic solution
• GANFORT®
Topical sterile ophthalmic solution

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Aerie Pharmaceuticals

Countries where clinical trial is conducted

Austria,  Belgium,  Czechia,  France,  Germany,  Hungary,  Italy,  Latvia,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Diurnal Intraocular Pressure by Goldmann Applanation Tonometry	Comparison of PG324 to Ganfort for mean intraocular pressure at specified timepoints at Week 2, Week 6 and Month 3.	Day 90