Non-arteritic Ischemic Optic Neuropathy, Optic Nerve Injuries
Conditions
Keywords
Ischemic Optic Neuropathy, Traumatic Neuropathy, Non Arteritic Ischemic Neuropathy (NAION)
Brief summary
The study objectives are to assess any changes in visual acuity and visual field observed following the administration of RPh201 during an overall treatment period of at least 13 consecutive weeks with an option to extended the treatment phase to another 13 weeks (26 weeks total), and at the follow-up visit at 3 month after end of treatment in patients with optic nerve neuropathy.
Interventions
DRUGRPh201
SC injection twice a week during 13/26 weeks
DRUGPlacebo
SC injection twice a week during 13/26 weeks
Sponsors
Regenera Pharma Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants, either men or women are ≥ 18 years of age. 2. Diagnosis of ischemic optic neuropathy unilateral or bilateral: 1. Traumatic Neuropathy 2. Ischemic optic neuropathy - Non Arteritic Ischemic Neuropathy (NAION) 3. Corrected Visual acuity equal or worse than 6/60 or visual field of less than 15 degrees or both. 4. Field of view with a reduction from 10 degrees to one quarter situations functions. 5. Participant understands the nature of the procedure and provides written informed consent prior to any study procedure. 6. Women of child bearing potential must use adequate birth-control precautions.
Exclusion criteria
1. Glaucoma 2. Neuropathy caused by tumors. 3. Neuropathy caused by infections 4. Mitochondrial optic neuropathies 5. Nutritional, Radiation, Toxic optic neuropathies 6. Retinal diabetic complications 7. Hereditary optic neuropathies 8. Patients with complete SCOTOMA beyond three quarters. 9. Clinical evidence for presence of infection. 10. Patient is receiving, or has received within one month prior to enrollment corticosteroids, immunosuppressive drugs, cytotoxic agents, radiation therapy and chemotherapy. 11. Patient has a history of alcohol or drug abuse within the last two years. 12. Female patients who are pregnant or nursing, or of childbearing potential and are not using adequate contraception. 13. Participation in another clinical trial within 60 days prior to the Screening Visit or during this study. 14. Clinically significant and/or uncontrolled condition or other significant medical disease 15. Clinically significant uncontrolled retinal disease (AMD)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Increase From Baseline in ETDRS Letters Read at 26 Weeks and Off-drug Follow-up Visit | 26/39 weeks | Best Corrected Visual Acuity (BCVA) was assessed at all the visits, with refraction as necessary. VA measurements were taken in a sitting position at a test distance of 4 meters using early treatment diabetic retinopathy study (ETDRS) charts. |
| Changes in Visual Field Observed Following the Treatment | 26 weeks | Visual field mean deviation (MD) changes from the screening at week 26 using with the HVF 24-2 FASTPAC program using the size III or Size V test stimulus |
| Changes Mean RNFL Thickness in NAION Eyes Change From Screening to Week 26 | 26 weeks | TMean RNFL thickness measured by OCT. The data are in microns, as measured with an Opko OCT machine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events Assessed by Vital Signs, Clinical Laboratory and Physical Exam | 26/39 weeks | Safety and tolerability multiple ascending SC doses as assessed by adverse events, vital signs, clinical laboratory and physical exam |
Countries
Israel
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RPh201 3/6 month treatment schedule, consisting of bi-weekly SC administration of the RPh201
RPh201: SC injection twice a week during 13/26 weeks | 13 |
| Placebo 3/6 month treatment schedule, consisting of bi-weekly SC administration of the Placebo
Placebo: SC injection twice a week during 13/26 weeks | 9 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Finished 13 weeks, chose not to extend | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | RPh201 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 2 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 7 Participants | 16 Participants |
| Age, Continuous | 61.46 years STANDARD_DEVIATION 8.1 | 60.33 years STANDARD_DEVIATION 5.8 | 61.00 years STANDARD_DEVIATION 7.6 |
| BMI | 29.16 kg per metre squared STANDARD_DEVIATION 4.24 | 34.77 kg per metre squared STANDARD_DEVIATION 5.52 | 31.46 kg per metre squared STANDARD_DEVIATION 5.46 |
| Height | 1.7 metres STANDARD_DEVIATION 0.12 | 1.7 metres STANDARD_DEVIATION 0.12 | 1.7 metres STANDARD_DEVIATION 0.12 |
| Region of Enrollment Israel | 13 participants | 9 participants | 22 participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 13 Participants |
| Weight | 82.8 kg STANDARD_DEVIATION 13.58 | 95.5 kg STANDARD_DEVIATION 24.54 | 88.0 kg STANDARD_DEVIATION 19.38 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 13 | 9 / 9 |
| serious Total, serious adverse events | 4 / 13 | 1 / 9 |
Outcome results
Primary
Changes in Visual Field Observed Following the Treatment
Visual field mean deviation (MD) changes from the screening at week 26 using with the HVF 24-2 FASTPAC program using the size III or Size V test stimulus
Time frame: 26 weeks
Population: Efficacy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RPh201 | Changes in Visual Field Observed Following the Treatment | Changes Visual Field size III | 7.85 dB | Standard Error 5.8 |
| RPh201 | Changes in Visual Field Observed Following the Treatment | Changes Visual Field size V | 0.41 dB | Standard Error 1.66 |
| Placebo | Changes in Visual Field Observed Following the Treatment | Changes Visual Field size III | 0.84 dB | Standard Error 1.47 |
| Placebo | Changes in Visual Field Observed Following the Treatment | Changes Visual Field size V | 0.49 dB | Standard Error 2.59 |
Primary
Changes Mean RNFL Thickness in NAION Eyes Change From Screening to Week 26
TMean RNFL thickness measured by OCT. The data are in microns, as measured with an Opko OCT machine.
Time frame: 26 weeks
Population: Efficacy
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RPh201 | Changes Mean RNFL Thickness in NAION Eyes Change From Screening to Week 26 | -4.6 µm | Standard Error 1.58 |
| Placebo | Changes Mean RNFL Thickness in NAION Eyes Change From Screening to Week 26 | -1.8 µm | Standard Error 2.08 |
Primary
Mean Increase From Baseline in ETDRS Letters Read at 26 Weeks and Off-drug Follow-up Visit
Best Corrected Visual Acuity (BCVA) was assessed at all the visits, with refraction as necessary. VA measurements were taken in a sitting position at a test distance of 4 meters using early treatment diabetic retinopathy study (ETDRS) charts.
Time frame: 26/39 weeks
Population: Efficacy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RPh201 | Mean Increase From Baseline in ETDRS Letters Read at 26 Weeks and Off-drug Follow-up Visit | Changes in BCVA from baseline to week 26 | 15 EDTRS Letters | Standard Error 4.6 |
| RPh201 | Mean Increase From Baseline in ETDRS Letters Read at 26 Weeks and Off-drug Follow-up Visit | changes in BCVA from baseline to 39 weeks | 9 EDTRS Letters | Standard Error 5.6 |
| Placebo | Mean Increase From Baseline in ETDRS Letters Read at 26 Weeks and Off-drug Follow-up Visit | Changes in BCVA from baseline to week 26 | 7 EDTRS Letters | Standard Error 5.4 |
| Placebo | Mean Increase From Baseline in ETDRS Letters Read at 26 Weeks and Off-drug Follow-up Visit | changes in BCVA from baseline to 39 weeks | 6 EDTRS Letters | Standard Error 4.7 |
Secondary
Number of Participants With Adverse Events Assessed by Vital Signs, Clinical Laboratory and Physical Exam
Safety and tolerability multiple ascending SC doses as assessed by adverse events, vital signs, clinical laboratory and physical exam
Time frame: 26/39 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RPh201 | Number of Participants With Adverse Events Assessed by Vital Signs, Clinical Laboratory and Physical Exam | Visual acuity ocular safety in fellow eye | 0 participants |
| RPh201 | Number of Participants With Adverse Events Assessed by Vital Signs, Clinical Laboratory and Physical Exam | Visual field ocular safety in fellow eye | 0 participants |
| Placebo | Number of Participants With Adverse Events Assessed by Vital Signs, Clinical Laboratory and Physical Exam | Visual acuity ocular safety in fellow eye | 1 participants |
| Placebo | Number of Participants With Adverse Events Assessed by Vital Signs, Clinical Laboratory and Physical Exam | Visual field ocular safety in fellow eye | 1 participants |