A Phase 1/2, RU-101 Ophthalmic Solution in Patients With Severe Dry Eye

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
R-Tech Ueno, Ltd.
ClinicalTrials.gov Identifier:
NCT01843894
First received: April 12, 2013
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

Objectives:

Primary

  • To determine the safety and tolerability of escalating doses of RU-101 for 4 weeks in patients with severe dry eye

Secondary

  • To explore the efficacy of RU-101
  • To explore optimal endpoints for future studies

Condition Intervention Phase
Dry Eye
Biological: RU-101
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1/2, First-in-Human, Double-Masked, Placebo-Controlled, Dose-Escalation Study Evaluating the Safety, Tolerability, and Efficacy of RU-101 Ophthalmic Solution in Patients With Severe Dry Eye

Resource links provided by NLM:


Further study details as provided by R-Tech Ueno, Ltd.:

Primary Outcome Measures:
  • Occular Adverse Events [ Time Frame: 56 dyas (stage1) 112 days (stage 2) ] [ Designated as safety issue: Yes ]

    The number of participants with a change from baseline in the following symptoms:

    • intraocular pressure (IOP)-The IOP assessment will be done using either a Goldmann applanation tonometer or digital tonometer.
    • slit lamp biomicroscopy
    • fundoscopy-A dilated fundoscopic examination including evaluation of the vitreous, optic nerve, macula and retina will be performed and any abnormalities will be evaluated on a 4-point scale (1-4; slight, moderate, severe, or very severe


Secondary Outcome Measures:
  • Symptoms [ Time Frame: 28days (stage 1) 3 months (stage2) ] [ Designated as safety issue: No ]

    The number of participants with a change from baseline in the following symptoms:

    • Symptom Assessment in Dry Eye (SANDE)
    • Ocular Surface Disease Index (OSDI)
    • Visual acuity (Early Treatment Diabetic Retinopathy Study [ETDRS] chart, high and 10% low contrast)

  • Signs [ Time Frame: 28days (stage 1) 3 months (stage2) ] [ Designated as safety issue: No ]

    The number of participants with a change from baseline in the following signs:

    • Tear break-up time (TBUT)
    • Corneal staining with fluorescein
    • Conjunctival staining with Lissamine Green
    • Corneal sensitivity
    • Schirmer test

  • Non-Occular Adverse Events [ Time Frame: 56 dyas (stage1) 112 days (stage 2) ] [ Designated as safety issue: Yes ]
    Number of AEs will be measured (vital signs, physical examination results, safety laboratory results, 12-lead electrocardiogram (ECG), and IP comfort assessment.


Enrollment: 104
Study Start Date: April 2013
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo
In Stage I, each patient will instill 1 drop of placebo into each eye, 6 times a day with at least 2 hours between each dose, for 28 days (4 weeks; a total of 168 doses to each eye). In Stage II, each patient will instill 1 drop into each eye, 6 times a day with at least 2 hours between each dose, for 84 days (12 weeks; a total of 504 doses to each eye).
Experimental: RU-101
In Stage I, each patient will instill 1 drop of RU-101 ophthalmic solution (5%, 10%, or 15%) into each eye, 6 times a day with at least 2 hours between each dose, for 28 days (4 weeks; a total of 168 doses to each eye). In Stage II, each patient will instill 1 drop of RU-101 ophthalmic solution (selected dose from Stage I) into each eye, 6 times a day with at least 2 hours between each dose, for 84 days (12 weeks; a total of 504 doses to each eye).
Biological: RU-101
Recombinant human serum albumin

Detailed Description:

This is a Phase 1/2, first-in-human, multicenter, dose escalation, double-masked, placebo controlled study consisting of two stages. In Stage I, 3 cohorts are planned to evaluate escalating doses of RU 101 ophthalmic solution, instilled 6 times daily into each eye for 4 weeks (28 days). Each cohort will comprise 4 patients randomized 3:1 to RU-101 or placebo. A masked safety data review will be performed prior to each dose escalation to determine if any dose limiting toxicities (DLTs) occurred and to define the MTD or highest dose to be used in Stage II. In Stage II, an expanded cohort will receive the dose defined in Stage I (MTD or highest dose if MTD is not reached), instilled 6 times daily into each eye for 12 weeks (84 days). The expanded cohort will comprise approximately 96 patients randomized 1:1 to RU-101 or placebo, provided in a double-masked manner.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients aged 18 to 80 years.
  2. Patients have had dry eye symptoms at least 4 months.
  3. Patients have the following signs in the worst eye:

    1. Corneal staining score with fluorescein staining ≥ 6/15 with at least one in the central
    2. Conjunctival staining score with Lissamine Green ≥ 2/18
  4. Patients who had been receiving treatment with eye drops of artificial tears, Restasis, or topical steroids but have had insufficient efficacy or have found these products to be intolerable. If using Restasis or topical steroids, patients must agree to a 30-day washout period prior to the first IP dose (Day 0).
  5. Female patients of child bearing potential must agree to have a urine pregnancy test performed at Screening (must be negative) and agree to use a medically acceptable form of birth control (e.g., intrauterine device, birth control pill, patch or subcutaneous implant, condoms, diaphragm, or abstinence) throughout the duration of IP instillation. Women considered capable of becoming pregnant include all females who have experienced menarche and who have not experienced menopause (as defined by amenorrhea for > 12 consecutive months) or have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy).

Exclusion Criteria:

  1. Presence of anterior eye diseases except dry eye.
  2. Intraocular pressure ≥ 22 mmHg at Screening.
  3. Use of any ophthalmic solutions (including over-the-counter [OTC] solutions), serum eye drops, or contact lenses during the Treatment Phase. Artificial tears are allowed during the Screening Phase but must not be used from the first dose (Day 0) through the Treatment Phase.
  4. Use of eye drops of Restasis or topical steroids within 30 days of the first dose (Day 0).
  5. Use of antihistamines, beta blockers, tricyclic antidepressants, or antidepressants with anticholinergic side effects during the Treatment Phase.
  6. Patients with previous corneal transplantation or laser-assisted in situ keratomileusis (LASIK).
  7. Presence of graft-versus-host disease (GVHD).
  8. Patients who have had other ocular surgery within 3 months prior to the first dose.
  9. Patients with punctal plugs or punctal cautery < 3 months prior to the first dose.
  10. Patients with severe dry eye due to Stevens-Johnson disease or ocular cicatricial pemphigoid.
  11. History of allergy to human serum protein products and/or any history of allergy to yeast.
  12. History of allergies to recombinant products, ophthalmic solutions, any constituents of RU 101, or any solutions planned for use in this study.
  13. Any significant chronic illness that, in the opinion of the Principal Investigator (PI), could interfere with the study parameters.
  14. Use of any investigational product or device within 30 days prior to the Screening Visit or during the study.
  15. Known history of alcohol and/or drug abuse within the past 12 months, which in the opinion of the PI could interfere with study compliance, outcome measures including safety parameters, and/or the general medical condition of the patient.
  16. Those unable in the opinion of the PI to comply fully with the study requirements.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01843894

Locations
United States, Virginia
Virginia Eye Consultants
Norfolk, Virginia, United States, 22655-5342
Sponsors and Collaborators
R-Tech Ueno, Ltd.
Investigators
Principal Investigator: John Sheppard, MD Virginia Ehe Consultants
  More Information

No publications provided

Responsible Party: R-Tech Ueno, Ltd.
ClinicalTrials.gov Identifier: NCT01843894     History of Changes
Other Study ID Numbers: RU-101-C001
Study First Received: April 12, 2013
Last Updated: August 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by R-Tech Ueno, Ltd.:
sever dry eye,keratoconjunctivitis sicca

Additional relevant MeSH terms:
Keratoconjunctivitis Sicca
Dry Eye Syndromes
Keratoconjunctivitis
Conjunctivitis
Conjunctival Diseases
Eye Diseases
Keratitis
Corneal Diseases
Lacrimal Apparatus Diseases
Pharmaceutical Solutions
Ophthalmic Solutions
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014