Clinical trial NCT03821415: Effects of RP101 in Post-menopausal Women With Dry Eye Syndrome
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dry Eye Syndromes
Keywords: Keratoconjunctivitis sicca
Dry Eye Disease
Slow-release
Ophthalmology
Topical Eye Disease
Lead sponsor: Redwood Pharma AB
Sponsor class: INDUSTRY
Collaborators: name: Cross Research S.A.
First posted: 2019-01-29
Enrollment: 104
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentre, randomised, double-masked, parallel-group, placebo-controlled Phase II study
Primary purpose: TREATMENT

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

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).

Eligibility 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

Primary outcomes:
measure: Schirmer's test type II (with anaesthesia)
timeFrame: From Screening up to 90 days
Secondary outcomes:
measure: Visual analogue scale (VAS) for ocular tolerability (foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision, redness, tearing, eyelid swelling and photophobia)
timeFrame: From Screening up to 90 days
measure: Symptom assessment in Dry Eye (SANDE)
timeFrame: From Screening up to 90 days
measure: Visual acuity assessment using an Early Treatment Diabetic Retinopathy Study [ETDRS] chart
timeFrame: From Screening up to 90 days
measure: Slit lamp examination (SLE)
timeFrame: From Screening up to 90 days
measure: TFBUT
timeFrame: From Screening up to 90 days
measure: Fundus ophthalmoscopy
timeFrame: From Screening up to 90 days
measure: Corneal fluorescein staining
timeFrame: From Screening up to 90 days
measure: Treatment-emergent Adverse Event (TEAEs)
timeFrame: From Screening up to 104 days
measure: 17-β-oestradiol serum concentrations
timeFrame: Day 1 and Day 90
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna - Department of Clinical Pharmacology
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald, Klinik und Poliklinik für Augenheilkunde
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz Augenklinik und Poliklinik Klinisches
city: München
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität München, Anstalt des öffentlichen Rechts Klinik und Poliklinik für Augenheilkunde
city: Budapest
country: Hungary
facility: Óbudai Egészség Centrum
city: Létavértes
country: Hungary
facility: Swan Med Hungary Kft.
city: Miskolc
country: Hungary
facility: MacroKlinika
city: Székesfehérvár
country: Hungary
facility: Mentaház Magánorvosi Központ
Study officials:
affiliation: Redwood Pharma AB
name: Ulf Björklund, MSc Pharm
role: STUDY_DIRECTOR
References:
citation: Schmidl D, Szalai L, Kiss OG, Schmetterer L, Garhofer G. A Phase II, Multicenter, Randomized, Placebo-Controlled, Double-Masked Trial of a Topical Estradiol Ophthalmic Formulation in Postmenopausal Women with Moderate-to-Severe Dry Eye Disease. Adv Ther. 2021 Apr;38(4):1975-1986. doi: 10.1007/s12325-021-01680-3. Epub 2021 Mar 12.