Effects of RP101 in Post-menopausal Women With Dry Eye Syndrome

• ClinicalTrials.gov Identifier: NCT03821415
• Recruitment Status: Completed
• First Posted: January 29, 2019
• Last Update Posted: December 20, 2019
• Sponsor: Redwood Pharma AB
• Collaborator: Cross Research S.A.
• Information provided by (Responsible Party): Redwood Pharma AB

Study Description

Brief Summary:

The main purpose of this study is to establish whether RP101 can reduce symptoms of dry eye syndrome in post-menopausal women.

Condition or disease	Intervention/treatment	Phase
Dry Eye Syndromes	Drug: RP101	Phase 2

Detailed Description:

Redwood Pharma is developing the novel ophthalmic product RP101 containing the known active substance 17β-oestradiol-3-phosphate and based upon the drug delivery platform IntelliGel which controls the active substance release. The novel formulation is planned to meet the still unmet medical need of an efficacious treatment against chronic dry eye in postmenopausal women.

The efficacy of the novel formulation RP101 will be investigated for the first time in the present multicentre, randomised, double-masked, parallel-group, placebo-controlled Phase II study in women post-menopausal for at least 3 years presenting with symptoms specific for dry eye syndrome of moderate to severe intensity.

The planned study will be conducted in Austria, Germany and Hungary. The primary objective of the study is to establish the effective dose/dose regimen of RP101 in these patients applying RP101 ophthalmic sterile solution or matching placebo (vehicle) once (q.d.) or twice a day (b.i.d.) for 3 months. One hundred (100) patients will be enrolled in this study. The subjects will be randomly assigned (1:1:1:1) to a treatment group and will receive one of the treatments for 90 consecutive days.

Evaluation of the clinical efficacy during and at the end of the treatment will be done on the basis of the Schirmer's test type II (with anaesthesia).

The secondary objectives of the study are:

• to evaluate the safety and tolerability of the treatment
• to evaluate the pharmacokinetics (PK) of serum 17β-oestradiol after the 1st and the last dose (only PK substudy).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 104 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Multicentre, randomised, double-masked, parallel-group, placebo-controlled Phase II study
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II, Multicentre, Randomised, Placebo-controlled, Doublemasked Trial of RP101 Ophthalmic Formulation Versus Vehicle in Post-menopausal Women With Moderate to Severe Dry Eye Syndrome
• Actual Study Start Date: January 18, 2019
• Actual Primary Completion Date: November 18, 2019
• Actual Study Completion Date: November 18, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 - RP101 0.05%; RP101 0.05% (w/w) 17β-oestradiol-3-phosphate ophthalmic sterile solution, one drop each eye every 12 h (b.i.d.) for 90 consecutive days	Drug: RP101; 17β-oestradiol-3-phosphate ophthalmic sterile solution; Other Name: 17β-oestradiol-3-phosphate
Experimental: 2 - RP101 0.1% / Placebo; RP101 0.1% (w/w) 17β-oestradiol-3-phosphate ophthalmic sterile solution, one drop each eye in the morning (q.d.) followed by one drop of placebo each eye in the evening for 90 consecutive days	Drug: RP101; 17β-oestradiol-3-phosphate ophthalmic sterile solution; Other Name: 17β-oestradiol-3-phosphate
Experimental: 3 - RP101 0.1%; RP101 0.1% (w/w) 17β-oestradiol-3-phosphate ophthalmic sterile solution, one drop each eye every 12 h (b.i.d.) for 90 consecutive days	Drug: RP101; 17β-oestradiol-3-phosphate ophthalmic sterile solution; Other Name: 17β-oestradiol-3-phosphate
Placebo Comparator: 4 - Placebo; RP101 matching placebo, ophthalmic sterile solution, one drop each eye every 12 h (b.i.d.) for 90 consecutive days	Drug: RP101; 17β-oestradiol-3-phosphate ophthalmic sterile solution; Other Name: 17β-oestradiol-3-phosphate

Outcome Measures

Primary Outcome Measures :

1. Schirmer's test type II (with anaesthesia) [ Time Frame: From Screening up to 90 days ]
   Schirmer's test uses sterile strips inserted into the eye to measure the basal aqueous tear secretion.

Secondary Outcome Measures :

1. Visual analogue scale (VAS) for ocular tolerability (foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision, redness, tearing, eyelid swelling and photophobia) [ Time Frame: From Screening up to 90 days ]
   It will be assigned by the patients using a 100 mm VAS.
2. Symptom assessment in Dry Eye (SANDE) [ Time Frame: From Screening up to 90 days ]
   The patient symptoms of ocular dryness and/or irritation will be quantified on a Visual Analogue Scale (VAS) 0-100 mm based on two questions that inquire about both severity and frequency of symptoms. The patients will evaluate their symptoms on the VAS scale giving the value they are feeling from none (0 mm) to an extreme value (100 mm).
3. Visual acuity assessment using an Early Treatment Diabetic Retinopathy Study [ETDRS] chart [ Time Frame: From Screening up to 90 days ]
   Best correction will be determined by careful refraction using a retroilluminated ETDRS 4 meter distance acuity chart. The correct number of letters read by the patient is recorded and evaluated.
4. Slit lamp examination (SLE) [ Time Frame: From Screening up to 90 days ]
   The SLE will be performed before the instillation of any dilating or anaesthetic eye drops or the fluorescein agent.
5. TFBUT [ Time Frame: From Screening up to 90 days ]
   Tear film break up time (TFBUT) will be measured by determining the time to tear break-up after instillation of sodium fluorescein solution into the inferior conjunctival culde-sac of each eye.
6. Fundus ophthalmoscopy [ Time Frame: From Screening up to 90 days ]
   The fundus examination will include ophthalmoscopic assessments of vitreous, macula, retina and optic nerve head for both eyes.
7. Corneal fluorescein staining [ Time Frame: From Screening up to 90 days ]
   The corneal fluorescein staining evaluates cornea and conjunctiva epithelium damage.
8. Treatment-emergent Adverse Event (TEAEs) [ Time Frame: From Screening up to 104 days ]
   All adverse events (AEs) derived by spontaneous, unsolicited reports of the subjects, by observation and by routine open questioning will be collected and reported.
9. 17-β-oestradiol serum concentrations [ Time Frame: Day 1 and Day 90 ]
   Using a fully validated analytical method.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Informed consent: signed written informed consent before inclusion in the study
• Sex and menopause: postmenopausal women; postmenopausal condition defined as final menstrual period at least 3 years before the screening
• Dry eye syndrome: patients with moderate to severe dry eye syndrome
• Tear film breakup time: TFBUT ≤ 10 sec in the worse eye (study eye)
• Visual acuity: corrected visual acuity ≥ 20/200 in each eye
• Symptoms: at least 2 of the typical dry eye syndrome symptoms since at least 3 months before the screening: foreign body sensation, burning/stinging, redness, tearing, pain, itching, blurred vision, photophobia, eyelid swelling, moisture and mucous discharge
• Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study

Exclusion Criteria:

• Meibomian gland dysfunction: severe Meibomian gland dysfunction defined as lid deformity, marked lid margin hyperaemia or severe Meibomian gland loss
• Ophthalmic treatment: current use of topical ophthalmic medications other than ocular lubricants or artificial tears within 30 days before the screening
• Ocular infection and inflammation: presence of any bacterial or viral or fungal infection in either eye or active inflammation not related to dry eye disease (i.e. follicular conjunctivitis, iris or preauricular adenopathy) in either eye
• Ophthalmic diseases: severe forms of ophthalmic surface diseases e.g. ocular pemphigoid, Sjögren's disease, exposure keratitis
• Ophthalmic surgery: history of ophthalmic surgery or trauma in the last 6 months; history of laser-assisted in situ keratomileusis (LASIK) in the previous 12 months
• Diseases: uncontrolled systemic diseases including cardiovascular, pulmonary and/or renal diseases, diabetes, hypertension; history of ovarian, breast or uterine cancer or unexplained vaginal bleeding
• Investigative drug studies: participation in the evaluation of any investigational product or medical device for 30 days before this study

Contacts and Locations

Locations

Austria

Medical University of Vienna - Department of Clinical Pharmacology

Vienna, Austria, 1090

Germany

Universitätsmedizin Greifswald, Klinik und Poliklinik für Augenheilkunde

Greifswald, Germany, 17475

Universitätsmedizin Mainz Augenklinik und Poliklinik Klinisches

Mainz, Germany, 55131

Klinikum rechts der Isar der Technischen Universität München, Anstalt des öffentlichen Rechts Klinik und Poliklinik für Augenheilkunde

München, Germany, 81675

Hungary

Óbudai Egészség Centrum

Budapest, Hungary, 1036

Swan Med Hungary Kft.

Létavértes, Hungary, 4281

MacroKlinika

Miskolc, Hungary, 3526

Mentaház Magánorvosi Központ

Székesfehérvár, Hungary, 8000

Sponsors and Collaborators

Redwood Pharma AB

Cross Research S.A.

Investigators

• Study Director: Ulf Björklund, MSc Pharm; Redwood Pharma AB

More Information

• Responsible Party: Redwood Pharma AB
• ClinicalTrials.gov Identifier: NCT03821415
• Other Study ID Numbers: RP101-200
• First Posted: January 29, 2019
• Last Update Posted: December 20, 2019
• Last Verified: December 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Redwood Pharma AB:

Keratoconjunctivitis sicca; Dry Eye Disease; Slow-release; Ophthalmology; Topical Eye Disease

Additional relevant MeSH terms:

Keratoconjunctivitis Sicca; Dry Eye Syndromes; Syndrome; Disease; Pathologic Processes; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Eye Diseases; Keratitis; Corneal Diseases; Lacrimal Apparatus Diseases; Estradiol; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs