A Dose-ranging Study to Evaluate the Safety and Efficacy of UNR844 in Subjects With Presbyopia. (READER)

A Randomized, Placebo-controlled, Double-masked, Multi-center, Dose-ranging Study to Evaluate the Safety, and Efficacy of UNR844 in Subjects With Presbyopia

Study of safety and efficacy of UNR844 in subjects with presbyopia.

Study Overview

• Status: Terminated
• Conditions: Presbyopia
• Intervention / Treatment: Drug: Placebo; Drug: UNR844

Detailed Description

This was a randomized, placebo-controlled, double-masked,multi-arm, parallel-group, multi-center 13-month study which consisted of:

• A 1 week run-in period
• A 3-month treatment course with UNR844 and/or Placebo
• A 9-month treatment holiday period Participants were randomized equally to one of five treatment arms: UNR844 5 mg/mL,UNR844 13.3 mg/mL, UNR844 23 mg/mL, UNR844 30 mg/mL, or Placebo eye drops twice-a-day for three months.

Participants underwent a 1 week run-in period where they were assessed for entry criteria during the Screening visit. During the run-in period, participants self-administered 1 drop of artificial tears twice-a-day (1 drop in the morning and 1 drop in the evening) in each eye at home. This run-in period was designed to help minimize any potential variability in distance corrected near visual acuity (DCNVA) caused due to initial ocular surface issues and help to establish an accurate baseline prior to randomization. The run-in period was to help exclude participants with a change in DCNVA of 0.10 logMAR difference between Screening and Baseline.

This study was conducted to determine the optimum dose of UNR844 treatment and the duration of effect of UNR844 treatment for further development.

• Study Type: Interventional
• Enrollment (Actual): 234
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2052
      • Novartis Investigative Site
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Novartis Investigative Site
• Canada
  • Quebec, Canada, G1S 4L8
    • Novartis Investigative Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 1H6
      • Novartis Investigative Site
  • Ontario
    • Kitchener, Ontario, Canada, N2A 0K5
      • Novartis Investigative Site
    • Waterloo, Ontario, Canada, N2L3G1
      • Novartis Investigative Site
• Japan
  • Osaka
    • Suita-city, Osaka, Japan, 565-0853
      • Novartis Investigative Site
  • Tokyo
    • Shinjuku ku, Tokyo, Japan, 160-0008
      • Novartis Investigative Site
• United States
  • California
    • Laguna Hills, California, United States, 92653
      • Novartis Investigative Site
    • Newport Beach, California, United States, 92663
      • Novartis Investigative Site
    • Newport Beach, California, United States, 92660
      • Novartis Investigative Site
  • Florida
    • Largo, Florida, United States, 33773
      • Novartis Investigative Site
  • Illinois
    • Lake Villa, Illinois, United States, 60046
      • Novartis Investigative Site
  • Kansas
    • Pittsburg, Kansas, United States, 66762
      • Novartis Investigative Site
  • Missouri
    • Washington, Missouri, United States, 63090
      • Novartis Investigative Site
  • Pennsylvania
    • Kingston, Pennsylvania, United States, 18704
      • Novartis Investigative Site
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57108
      • Novartis Investigative Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Novartis Investigative Site
    • Smyrna, Tennessee, United States, 37167
      • Novartis Investigative Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent must be obtained before any assessment is performed
• Impaired near vision in each eye and when using both eyes, without any near correction
• Need a certain level of near correction

Exclusion Criteria:

• Impaired distance vision in either eye, with distance correction (if any)
• Severe short- or long-sightedness
• Any significant medical or clinical conditions affecting vision, the eyes or general health

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Ophthalmic Solution; placebo ophthalmic solution; one drop twice-a-day for three months	Drug: Placebo; Placebo; Other Names: Vehicle
Experimental: UNR844 5 mg/mL; UNR844 5 mg/mL ophthalmic solution; one drop twice-a-day for three months	Drug: UNR844; Ophthalmic solution for topical ocular administration; Other Names: EV06
Experimental: UNR844 13.3 mg/mL; UNR844 13.3 mg/mL 1 ophthalmic solution; one drop twice-a-day for three months	Drug: UNR844; Ophthalmic solution for topical ocular administration; Other Names: EV06
Experimental: UNR844 23 mg/mL; UNR844 23 mg/mL ophthalmic solution; one drop twice-a-day for three months	Drug: UNR844; Ophthalmic solution for topical ocular administration; Other Names: EV06
Experimental: UNR844 30 mg/mL; UNR844 30 mg/mL ophthalmic solution; one drop twice-a-day for three months	Drug: UNR844; Ophthalmic solution for topical ocular administration; Other Names: EV06

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize Dose-response of UNR844 for Change From Baseline in Binocular Distance-corrected Near Visual Acuity (DCNVA) at Month 3	Characterize dose response of UNR844 as measured by change from baseline at Month 3 in binocular DCNVA (without near correction) in Logarithm of Minimum Angle of Resolution (logMAR), at 40cm. A low logMAR score represents good vision while a high logMAR score represents bad vision.	Baseline, Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize Dose Response of UNR844 as Measured by Change From Baseline in Monocular (Worse-seeing Eye) Distance-corrected Near Visual Acuity (DCNVA) at Month 3	Characterize dose response of UNR844 as measured by change from baseline at Month 3 in monocular (worse-seeing eye) DCNVA in Logarithm of Minimum Angle of Resolution (logMAR), at 40 cm. A low logMAR score represents good vision while a high logMAR score represents bad vision.	Baseline, Month 3
Characterize Dose Response of UNR844 as Measured by Change From Baseline in Monocular (Better-seeing Eye) Distance-corrected Near Visual Acuity (DCNVA) at Month 3	Characterize dose response of UNR844 as measured by change from baseline at Month 3 in monocular (better-seeing eye) DCNVA in Logarithm of Minimum Angle of Resolution (logMAR), at 40cm. A low logMAR score represents good vision while a high logMAR score represents bad vision.	Baseline, Month 3
Percentage of Participants Gaining at Least 0.30 logMAR in Binocular Distance-corrected Near Visual Acuity (DCNVA) (Without Near Correction) From Baseline at Month 3	Percentage of participants gaining at least 0.3 logMAR in binocular DCNVA compared to baseline at Month 3. DCNVA is measured in Logarithm of Minimum Angle of Resolution (logMAR) at 40 cm, with subjects corrected for any distance refraction error. A low logMAR score represents good vision while a high logMAR score represents bad vision. Percentages were derived from Rubin's rule by integrating all results from multiple imputations. For subjects with missing DCNVA at Month 3, the value of DCNVA was imputed and dichotomized to derive the endpoint of gaining of 3 lines.	Baseline, Month 3
Percentage of Participants Gaining at Least 0.30 logMAR in Monocular (Worse-seeing Eye) Distance-corrected Near Visual Acuity (DCNVA) (Without Near Correction) From Baseline at Month 3	Percentage of participants gaining at least 0.3 logMAR in monocular (worse-seeing eye) DCNVA compared to baseline at Month 3. DCNVA is measured in Logarithm of Minimum Angle of Resolution (logMAR) at 40 cm, with subjects corrected for any distance refraction error. A low logMAR score represents good vision while a high logMAR score represents bad vision. Percentages were derived from Rubin's rule by integrating all results from multiple imputations. For subjects with missing DCNVA at Month 3, the value of DCNVA was imputed and dichotomized to derive the endpoint of gaining of 3 lines.	Baseline, Month 3
Percentage of Participants Gaining at Least 0.30 logMAR in Monocular (Better-seeing Eye) Distance-corrected Near Visual Acuity (DCNVA) (Without Near Correction) From Baseline at Month 3	Percentage of participants gaining at least 0.3 logMAR in monocular (better-seeing eye) DCNVA compared to baseline at Month 3. DCNVA is measured in Logarithm of Minimum Angle of Resolution (logMAR) at 40 cm, with subjects corrected for any distance refraction error. A low logMAR score represents good vision while a high logMAR score represents bad vision. Percentages were derived from Rubin's rule by integrating all results from multiple imputations. For subjects with missing DCNVA at Month 3, the value of DCNVA was imputed and dichotomized to derive the endpoint of gaining of 3 lines.	Baseline, Month 3

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2021
• Primary Completion (Actual): July 27, 2022
• Study Completion (Actual): October 14, 2022

Study Registration Dates

• First Submitted: March 16, 2021
• First Submitted That Met QC Criteria: March 16, 2021
• First Posted (Actual): March 19, 2021

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Presbyopia; UNR844; lens; loss of elasticity in lens; lens disorder; loss of near vision; farsightedness
• Additional Relevant MeSH Terms: Eye Diseases; Refractive Errors; Presbyopia
• Other Study ID Numbers: CUNR844A2202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No