Efficacy & Safety of RPh201 Treatment in Patients With Previous Nonarteritic Anterior Ischemic Optic Neuropathy (NAION)

NCT03547206 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: RGN-ON-002
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 15

Brief Summary

This study is designed as a double-masked, randomized, placebo-controlled, clinical study to evaluate the efficacy and safety of subcutaneous (SC) administration of RPh201 in participants with previous NAION. All participants enrolled in Cohort A of the study will have a documented history of NAION for at least 12 months and at most, five years prior to enrollment. Participants enrolled in Cohort B of the study will have a documented history of NAION for at least 6 months and at most, three years prior to enrollment.

Conditions

Nonarteritic Anterior Ischemic Optic Neuropathy

Keywords

NAION; ischemic optic neuropathy

Outcome Measures

Primary Outcomes (2)

• The change in number of best-corrected visual acuity (BCVA) letters from baseline to Week 26 (Cohort A) measured using electronic visual acuity (EVA).

  Visual acuity

  Week 26 or Week 12

• The change in number of best-corrected visual acuity (BCVA) letters from baseline to Week 12 (Cohort B) measured using electronic visual acuity (EVA).

  Visual acuity

  Week 12

Secondary Outcomes (5)

• The proportion of study eyes improving by a 15-letter score or more in BCVA from baseline to Week 26 using EVA (Cohort A).

  Week 26

• The proportion of study eyes improving by a 15-letter score or more in BCVA from baseline to Week 12 (Cohort B).

  Week 12

• The proportion of study eyes improving from baseline in five or more locations of the Humphrey visual field (HVF) 24-2 full-threshold with the size V stimulus on the glaucoma change probability map (GCPM) at the 5% level by group.

  Week 26

• The proportion of study eyes improving by a 10-letter score or more in BCVA from baseline to Week 26 (Cohort A) using EVA.

  Week 26

• The proportion of study eyes improving by a 10-letter score or more in BCVA from baseline to Week 12 (Cohort B) using EVA.

  Week 12

Other Outcomes (9)

• The change in sensitivity on HVF-24-2 full-threshold with the size V stimulus.

  Week 26

• The change in number of BCVA letters

  Week 52

• The proportion of study eyes improving by a 10-letter score or more in BCVA from baseline using EVA.

  Week 52

Study Arms (4)

RPh201 Cohort A

EXPERIMENTAL

A 26-week schedule consisting of twice-weekly subcutaneous administration of 400 μL of the Investigational Medical Product (IMP) (20 mg RPh201).

Drug: RPh201 Cohort A

Placebo Cohort A

PLACEBO COMPARATOR

A 26-week schedule consisting of twice-weekly subcutaneous administration of 400 μL of the vehicle control.

Other: Placebo Cohort A

RPh201 Cohort B

EXPERIMENTAL

A 12-week schedule consisting of four-times-per-week subcutaneous administration of 400 μL of the Investigational Medical Product (IMP) (20 mg RPh201).

Drug: RPh201 Cohort B

Placebo Cohort B

PLACEBO COMPARATOR

A 12-week schedule consisting of four-times-per-week subcutaneous administration of 400 μL of the vehicle control.

Other: Placebo Cohort B

Interventions

RPh201 Cohort A DRUG

RPh201 is a proprietary, isolated botanical extract of gum mastic for treatment of nonarteritic anterior ischemic optic neuropathy (NAION).

RPh201 Cohort A

Placebo Cohort A OTHER

The placebo is composed of RPh-201 excipients (cottonseed oil stabilized with butylated hydroxytoluene \[BHT\]).

Also known as: Cottonseed oil

Placebo Cohort A

RPh201 Cohort B DRUG

RPh201 is a proprietary, isolated botanical extract of gum mastic for treatment of nonarteritic anterior ischemic optic neuropathy (NAION).

RPh201 Cohort B

Placebo Cohort B OTHER

The placebo is composed of RPh-201 excipients (cottonseed oil stabilized with butylated hydroxytoluene \[BHT\]).

Placebo Cohort B

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant must be 50 years of age or older at the time of the NAION episode in the study eye. This means that the participant's age at enrollment must be greater than or equal to the sum of 50 plus the number of years since NAION (e.g., at least 52 years of age if the episode was two years prior).
• The participant must understand the nature of the procedure and provide written informed consent prior to any study procedure.
• The participant has a definitive clinical diagnosis of NAION in the study eye that developed at least 12 months before randomization. Specifically, the disc swelling must have been observed and documented (by examination, OCT or photograph) by an ophthalmologist or neuro-ophthalmologist who previously examined the participant at the time of the NAION episode in the study eye during the acute episode.
• The participant's study eye must have disc pallor (global or segmental) present.
• The participant's study eye must have stable visual acuity (see Sections 5.3.3 and 5.3.4).
• Using the study eye, the participant must read at least 20 and at most 66 EVA letters with best-corrected vision, at each Screening visit.
• The participant's study eye must have a HVF 24-2 SITA Standard visual field using spot size III with mean deviation -5 dB or worse and with a visual field defect compatible with NAION in the study eye (criteria in the MOP).

You may not qualify if:

• The participant has received treatment for cancer within 12 months prior to enrollment (excluding localized basal cell carcinoma or localized squamous cell carcinoma) or had past diagnosis of cancer adjacent to the afferent visual pathway or had past diagnosis of metastatic cancer.
• The participant had surgery, requiring general anesthesia with intubation, within 30 days prior to enrollment.
• The participant is pregnant or a woman of child-bearing potential not using an acceptable method of contraception (per Section 4.1 of the protocol).
• The participant is breast-feeding or plans to breast-feed.
• The participant has had treatment with drugs that have potential neuroprotective or toxic effects on the optic nerve or retina (e.g., ethambutol, amiodarone, linezolid, hydroxychloroquine, fingolimod, brimonidine) within 6 months prior to enrollment.
• The participant has participated in another interventional clinical trial within 60 days prior to enrollment, or previously participated in another clinical trial of RPh201 at any time.
• The participant has been receiving or has received within three months prior to enrollment, corticosteroids (except topical steroids, steroid inhalers or intermittent injections into a joint or back), or immunosuppressive drugs.
• The participant has a medical condition, social or psychological issue, or other condition which, in the judgment of the investigator, could be a safety concern or preclude the individual from completing the protocol.
• The participant has a known allergy to cottonseed oil.
• The participant is planning to move and not relocate near a study site and is unwilling to travel for appointments.
• The participant cannot self-administer or arrange for administration of the IP.
• The participant has one or more of the following abnormal test results at screening:
• Erythrocyte Sedimentation Rate (ESR) above age/2 for men or \[age + 10\]/2 for women, as measured by Westergren method or equivalent.
• Platelets \>400,000 mm3
• C-reactive protein (CRP) greater than two times the laboratory upper limit of normal.

Sponsors & Collaborators

• Regenera Pharma Ltd: lead

Study Sites (15)

Byers Eye Institute at Stanford University

Palo Alto, California, 94303, United States

Location

UCLA Doheny Eye Center

Pasadena, California, 91105, United States

Location

The Eye Care Group

Orange, Connecticut, 06477, United States

Location

The Eye Care Group

Waterbury, Connecticut, 06708, United States

Location

Anne Bates Leach Eye Hospital/Bascom Palmer Eye Institute

Miami, Florida, 33136, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

NorthShore Medical Group

Glenview, Illinois, 60026, United States

Location

Bethesda Neurology, LLC

Rockville, Maryland, 20852, United States

Location

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

Washington University Ophthalmology

St Louis, Missouri, 63108, United States

Location

New York Eye and Ear Infirmary of Mount Sinai

New York, New York, 10003, United States

Location

Wills Eye Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Charleston Neuroscience Institute

Ladson, South Carolina, 29456, United States

Location

Neuro-Eye Clinical Trials, Inc.

Houston, Texas, 77005, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

• Rath EZ, Hazan Z, Adamsky K, Solomon A, Segal ZI, Levin LA. Randomized Controlled Phase 2a Study of RPh201 in Previous Nonarteritic Anterior Ischemic Optic Neuropathy. J Neuroophthalmol. 2019 Sep;39(3):291-298. doi: 10.1097/WNO.0000000000000786.

  PMID: 31430268 BACKGROUND

Related Links

• Randomized Controlled Phase 2a Study of RPh201 in Previous Nonarteritic Anterior Ischemic Optic Neuropathy

MeSH Terms

Conditions

Optic Neuropathy, Ischemic

Interventions

Cottonseed Oil

Condition Hierarchy (Ancestors)

Optic Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases; Eye Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fats, Unsaturated; Plant Oils; Oils; Plant Preparations; Biological Products; Complex Mixtures; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Leonard A Levin, M.D., Ph.D.

  McGill University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All clinic staff and participants will be masked to group assignments. Only the Data and Safety Monitoring Board (DSMB) and designated unmasked staff at the Coordinating Center will have access to the group assignments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2018
• First Posted: June 6, 2018
• Study Start: July 10, 2018
• Primary Completion: September 27, 2020
• Study Completion: September 27, 2020
• Last Updated: October 12, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)