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

NCT ID: NCT03547206

Last Updated: 2020-10-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

165 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-10

Study Completion Date

2020-09-27

Brief Summary

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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.

Detailed Description

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This study is designed as a double-masked, randomized, placebo-controlled, clinical study to evaluate the efficacy and safety of SC administration of RPh201 in participants with previous NAION.

Following a screening phase of 1-8 weeks, participants will attend a baseline visit in which they will undergo testing and visual function assessments. Participants then will be randomized to receive RPh201 or control.

Cohort A After randomization, participants will begin a 26-week schedule consisting of twice-weekly treatment. Participants will return to the clinic for visits at Week 1, Week 4, Week 12 and Week 26 and Week 52

Cohort B After randomization, participants will begin a 12-week schedule consisting of four-times-per-week treatment. Participants will return to the clinic for visits at Week 4 and Week 12.

Safety and efficacy parameters will be recorded throughout the duration of the study.

Conditions

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Nonarteritic Anterior Ischemic Optic Neuropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
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.

Study Groups

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RPh201 Cohort A

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

Group Type EXPERIMENTAL

RPh201 Cohort A

Intervention Type DRUG

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

Placebo Cohort A

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

Group Type PLACEBO_COMPARATOR

Placebo Cohort A

Intervention Type OTHER

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

RPh201 Cohort B

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

Group Type EXPERIMENTAL

RPh201 Cohort B

Intervention Type DRUG

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

Placebo Cohort B

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

Group Type PLACEBO_COMPARATOR

Placebo Cohort B

Intervention Type OTHER

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

Interventions

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RPh201 Cohort A

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

Intervention Type DRUG

Placebo Cohort A

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

Intervention Type OTHER

RPh201 Cohort B

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

Intervention Type DRUG

Placebo Cohort B

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

Intervention Type OTHER

Other Intervention Names

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Cottonseed oil

Eligibility Criteria

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Inclusion Criteria

1. 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).
2. The participant must understand the nature of the procedure and provide written informed consent prior to any study procedure.
3. 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.
4. The participant's study eye must have disc pallor (global or segmental) present.
5. The participant's study eye must have stable visual acuity (see Sections 5.3.3 and 5.3.4).
6. 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.
7. 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).


1. 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).
2. The participant must understand the nature of the procedure and provide written informed consent prior to any study procedure.
3. The participant has a definitive clinical diagnosis of NAION in the study eye that developed at least 6 months and no more than 3 years 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.
4. The participant's study eye must have disc pallor (global or segmental) present.
5. The participant's study eye must have stable visual acuity (see Sections 5.3.3 and 5.3.4).
6. 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.

Exclusion Criteria

1. 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.
2. The participant had surgery, requiring general anesthesia with intubation, within 30 days prior to enrollment.
3. 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).
4. The participant is breast-feeding or plans to breast-feed.
5. 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.
6. 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.
7. 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.
8. 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.
9. The participant has a known allergy to cottonseed oil.
10. The participant is planning to move and not relocate near a study site and is unwilling to travel for appointments.
11. The participant cannot self-administer or arrange for administration of the IP.
12. 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.
* Severe anemia (Hgb \< 10)
13. The participant has symptoms, signs, and/or diagnosis of giant cell arteritis at any time.
14. The participant has any other optic neuropathies (e.g., optic neuritis or glaucoma) in either or both eyes (other than self-limited optic neuropathies in the non-study eye, such as past traumatic optic neuropathy or past transient steroid-induced glaucoma due to localized steroid administration).
15. The participant has systemic inflammatory or infectious disease associated with optic neuropathy or ocular disease.
16. The participant has a history of uveitis in the study eye within the last 10 years.
17. The participant's study eye has an ocular condition that appears consistent with a reduction in visual acuity to \<20/25, diabetic retinopathy beyond mild non-proliferative diabetic retinopathy not involving the macula, or vision-threatening macula disease.
18. The participant has a visual field defect with homonymous non-altitudinal features or a defect that respects the vertical meridian.


1. 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.
2. The participant had surgery, requiring general anesthesia with intubation, within 30 days prior to enrollment.
3. 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).
4. The participant is breast-feeding or plans to breast-feed.
5. 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.
6. 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. Participants who were randomized into the placebo arm of Cohort A of this protocol are eligible for screening for Cohort B.
7. 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.
8. 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.
9. The participant has a known allergy to cottonseed oil.
10. The participant is planning to move and not relocate near a study site and is unwilling to travel for appointments.
11. The participant cannot self-administer or arrange for administration of the IP.
12. The participant has one or more of the following abnormal test results at screening:

1. Erythrocyte Sedimentation Rate (ESR) above age/2 for men or \[age + 10\]/2 for women, as measured by Westergren method or equivalent.
2. Platelets \>400,000 mm3
3. C-reactive protein (CRP) greater than two times the laboratory upper limit of normal.
4. Severe anemia (Hgb \< 10 g/dL)
13. The participant has symptoms, signs, and/or diagnosis of giant cell arteritis at any time.
14. The participant has any other optic neuropathies (e.g., optic neuritis or glaucoma) in either or both eyes (other than self-limited optic neuropathies in the non-study eye, such as past traumatic optic neuropathy or past transient steroid-induced glaucoma due to localized steroid administration).
15. The participant has systemic inflammatory or infectious disease associated with optic neuropathy or ocular disease.
16. The participant has a history of uveitis in the study eye within the last 10 years.
17. The participant's study eye has an ocular condition that appears consistent with a reduction in visual acuity to \<20/25, diabetic retinopathy beyond mild non-proliferative diabetic retinopathy not involving the macula, or vision-threatening macula disease.
18. The participant has a visual field defect with homonymous non-altitudinal features or a defect that respects the vertical meridian.
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Regenera Pharma Ltd

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Leonard A Levin, M.D., Ph.D.

Role: STUDY_CHAIR

McGill University

Locations

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Byers Eye Institute at Stanford University

Palo Alto, California, United States

Site Status

UCLA Doheny Eye Center

Pasadena, California, United States

Site Status

The Eye Care Group

Orange, Connecticut, United States

Site Status

The Eye Care Group

Waterbury, Connecticut, United States

Site Status

Anne Bates Leach Eye Hospital/Bascom Palmer Eye Institute

Miami, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

NorthShore Medical Group

Glenview, Illinois, United States

Site Status

Bethesda Neurology, LLC

Rockville, Maryland, United States

Site Status

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, United States

Site Status

Washington University Ophthalmology

St Louis, Missouri, United States

Site Status

New York Eye and Ear Infirmary of Mount Sinai

New York, New York, United States

Site Status

Wills Eye Hospital

Philadelphia, Pennsylvania, United States

Site Status

Charleston Neuroscience Institute

Ladson, South Carolina, United States

Site Status

Neuro-Eye Clinical Trials, Inc.

Houston, Texas, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 31430268 (View on PubMed)

Related Links

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https://insights.ovid.com/crossref?an=00041327-201909000-00001

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

Other Identifiers

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RGN-ON-002

Identifier Type: -

Identifier Source: org_study_id

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