Ocular Hypertension, Open Angle Glaucoma
Conditions
Brief summary
The objective of this clinical study is to evaluate the safety and efficacy of NCX 470 Ophthalmic Solution in lowering intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma. In the adaptive dose selection phase of the trial, subjects will be randomized in a 1:1:1 ratio to one of two doses of NCX 470 (0.065% or 0.1%) or to latanoprost 0.005%. Following the selection of one dose of NCX 470, subjects will be randomized in a 1:1 ratio to the chosen dose of NCX 470 or to latanoprost 0.005%.
Interventions
DRUGNCX 470 0.065% (initial phase of trial)
NCX 470 Ophthalmic Solution, 0.065% (initial phase of trial)
DRUGLatanoprost 0.005% (initial phase of trial)
Latanoprost Ophthalmic Solution, 0.005%
DRUGNCX 470 0.1% (initial phase of trial)
NCX 470 Ophthalmic Solution, 0.1%
DRUGNCX 470 0.1% (remainder of trial)
NCX 470 Ophthalmic Solution, 0.1%
DRUGLatanoprost 0.005% (remainder of trial)
Latanoprost Ophthalmic Solution, 0.005%
Sponsors
Nicox Ophthalmics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
double-masked
Eligibility
Sex/Gender
ALL
Age
18 Years to 84 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of open-angle glaucoma or ocular hypertension in both eyes * Qualifying IOP at 3 time points through the day at 2 visits following washout of IOP-lowering medication, if applicable * Qualifying best-corrected visual acuity in each eye * Ability to provide informed consent and follow study instructions
Exclusion criteria
* Narrow anterior chamber angles or disqualifying corneal thickness in either eye * Clinically significant ocular disease in either eye * Previous complicated surgery or certain types of glaucoma surgery in either eye * Incisional ocular surgery or severe trauma in either eye within the past 6 months * Uncontrolled systemic disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean IOP Reduction From Time-Matched Baseline at the 8AM and 4PM Time-Points at Week 2, Week 6, and Month 3 | Baseline, Week 2, Week 6, and Month 3 | The analysis performed as part of the Adaptive Dose Phase of the study was to evaluate the efficacy and safety of both concentrations of NCX 470 compared to Latanoprost. The primary endpoint for the interim analysis was mean diurnal IOP. Subsequent to the interim analysis at Week 2, the NCX 470 0.065% arm was discontinued and the primary analysis only included NCX 470 0.1% vs Latanoprost. The primary efficacy outcome results are reported for the NCX 470 0.1% and Latanoprost 0.005% treatment groups at Week 2, Week 6, and Month 3. As prespecified in the Statistical Analysis Plan, mean change from baseline in time-matched IOP was not calculated for the 0.065% group. The study eye was defined as the eye with the highest mean diurnal intraocular pressure (IOP) value at baseline (or right eye if both eyes had the same IOP value at baseline). The fellow eye was followed for safety. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reduction From Baseline in Mean Diurnal IOP at Week 2, Week 6, and Month 3 in the Study Eye | Baseline, Week 2, Week 6, and Month 3 | Subjects in the NCX 470 0.065% treatment group were discontinued at Week 2 based upon the results of the planned, interim analysis. Subjects in the NCX 470 0.1% and Latanoprost 0.005% treatment groups continued for 3 months. Participants used medication in both eyes for 3 months with 1 eye designated as study eye at baseline. The study eye was defined as the eye with the highest mean diurnal intraocular pressure (IOP) value at baseline (or right eye if both eyes had the same IOP value at baseline). |
| Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | 3 months | Safety and tolerability based on number subjects with treatment emergent ocular adverse events. |
| Rate of Discontinuation | 3 months | Number of subjects discontinued from the study. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from 56 ophthalmologists' clinics in the US and 1 clinic in China. The first participant for the study was screened in June 2020 and the last participant exited the trial in September 2022.
Pre-assignment details
Participants were consented and screened for eligibility. Subjects underwent a medication wash-out. Eligible subjects meeting IOP criteria were randomized to 1 of 3 groups. All participants dosed once daily in both eyes. After 30 subjects in all 3 arms completed 2 weeks on drug, a planned, Adaptive Analysis was performed. Based upon the results of this analysis, enrollment continued in the NCX 470 0.1% and latanoprost 0.005% groups and the NCX 0.065% arm was discontinued.
Participants by arm
| Arm | Count |
|---|---|
| NCX 470 0.065% NCX 470 Ophthalmic Solution, 0.065% dosed once daily to both eyes | 30 |
| NCX 470 0.1% NCX 470 Ophthalmic Solution, 0.1% dosed once daily to both eyes | 328 |
| Latanoprost 0.005% Latanoprost Ophthalmic Solution, 0.005% dosed once daily to both eyes | 333 |
| Total | 691 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 8 | 6 |
| Overall Study | Due to adaptive design | 3 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 4 |
| Overall Study | Other Reason | 0 | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Sponsor or IRB Decision | 0 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 3 | 3 |
Baseline characteristics
| Characteristic | NCX 470 0.065% | Total | Latanoprost 0.005% | NCX 470 0.1% |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 19 Participants | 338 Participants | 159 Participants | 160 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 353 Participants | 174 Participants | 168 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 133 Participants | 67 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 555 Participants | 265 Participants | 267 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 8 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 228 Participants | 109 Participants | 110 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 448 Participants | 216 Participants | 212 Participants |
| Region of Enrollment China | 0 participants | 1 participants | 1 participants | 0 participants |
| Region of Enrollment United States | 30 participants | 690 participants | 332 participants | 328 participants |
| Sex: Female, Male Female | 17 Participants | 405 Participants | 188 Participants | 200 Participants |
| Sex: Female, Male Male | 13 Participants | 286 Participants | 145 Participants | 128 Participants |
| Time-Matched IOP Time-Matched IOP 4PM | 25.15 mmHg STANDARD_DEVIATION 2.589 | 25.36 mmHg STANDARD_DEVIATION 2.489 | 25.40 mmHg STANDARD_DEVIATION 2.422 | 25.52 mmHg STANDARD_DEVIATION 2.455 |
| Time-Matched IOP Time-Matched IOP 8AM | 28.07 mmHg STANDARD_DEVIATION 2.286 | 28.19 mmHg STANDARD_DEVIATION 2.099 | 28.22 mmHg STANDARD_DEVIATION 2.011 | 28.28 mmHg STANDARD_DEVIATION 2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 328 | 2 / 333 |
| other Total, other adverse events | 12 / 30 | 112 / 328 | 32 / 333 |
| serious Total, serious adverse events | 0 / 30 | 4 / 328 | 3 / 333 |
Outcome results
Primary
Mean IOP Reduction From Time-Matched Baseline at the 8AM and 4PM Time-Points at Week 2, Week 6, and Month 3
The analysis performed as part of the Adaptive Dose Phase of the study was to evaluate the efficacy and safety of both concentrations of NCX 470 compared to Latanoprost. The primary endpoint for the interim analysis was mean diurnal IOP. Subsequent to the interim analysis at Week 2, the NCX 470 0.065% arm was discontinued and the primary analysis only included NCX 470 0.1% vs Latanoprost. The primary efficacy outcome results are reported for the NCX 470 0.1% and Latanoprost 0.005% treatment groups at Week 2, Week 6, and Month 3. As prespecified in the Statistical Analysis Plan, mean change from baseline in time-matched IOP was not calculated for the 0.065% group. The study eye was defined as the eye with the highest mean diurnal intraocular pressure (IOP) value at baseline (or right eye if both eyes had the same IOP value at baseline). The fellow eye was followed for safety.
Time frame: Baseline, Week 2, Week 6, and Month 3
Population: Participants used medication in both eyes for 3 months with 1 eye designated as study eye at baseline. The study eye was defined as the eye with the highest mean diurnal intraocular pressure (IOP) value at baseline (or right eye if both eyes had the same IOP value at baseline).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NCX 470 0.1% | Mean IOP Reduction From Time-Matched Baseline at the 8AM and 4PM Time-Points at Week 2, Week 6, and Month 3 | Mean change from baseline - Week 2 8AM | -9.43 mmHg | Standard Deviation 3.443 |
| NCX 470 0.1% | Mean IOP Reduction From Time-Matched Baseline at the 8AM and 4PM Time-Points at Week 2, Week 6, and Month 3 | Mean change from baseline - Week 2 4PM | -8.01 mmHg | Standard Deviation 3.379 |
| NCX 470 0.1% | Mean IOP Reduction From Time-Matched Baseline at the 8AM and 4PM Time-Points at Week 2, Week 6, and Month 3 | Mean change from baseline - Week 6 8AM | -9.69 mmHg | Standard Deviation 3.129 |
| NCX 470 0.1% | Mean IOP Reduction From Time-Matched Baseline at the 8AM and 4PM Time-Points at Week 2, Week 6, and Month 3 | Mean change from baseline - Week 6 4PM | -8.18 mmHg | Standard Deviation 3.093 |
| NCX 470 0.1% | Mean IOP Reduction From Time-Matched Baseline at the 8AM and 4PM Time-Points at Week 2, Week 6, and Month 3 | Mean change from baseline - Month 3 8AM | -9.61 mmHg | Standard Deviation 3.196 |
| NCX 470 0.1% | Mean IOP Reduction From Time-Matched Baseline at the 8AM and 4PM Time-Points at Week 2, Week 6, and Month 3 | Mean change from baseline - Month 3 4PM | -8.00 mmHg | Standard Deviation 3.026 |
| Latanoprost 0.005% | Mean IOP Reduction From Time-Matched Baseline at the 8AM and 4PM Time-Points at Week 2, Week 6, and Month 3 | Mean change from baseline - Month 3 8AM | -9.39 mmHg | Standard Deviation 3.345 |
| Latanoprost 0.005% | Mean IOP Reduction From Time-Matched Baseline at the 8AM and 4PM Time-Points at Week 2, Week 6, and Month 3 | Mean change from baseline - Week 2 8AM | -8.85 mmHg | Standard Deviation 3.349 |
| Latanoprost 0.005% | Mean IOP Reduction From Time-Matched Baseline at the 8AM and 4PM Time-Points at Week 2, Week 6, and Month 3 | Mean change from baseline - Week 6 4PM | -7.14 mmHg | Standard Deviation 3.283 |
| Latanoprost 0.005% | Mean IOP Reduction From Time-Matched Baseline at the 8AM and 4PM Time-Points at Week 2, Week 6, and Month 3 | Mean change from baseline - Week 2 4PM | -7.11 mmHg | Standard Deviation 3.33 |
| Latanoprost 0.005% | Mean IOP Reduction From Time-Matched Baseline at the 8AM and 4PM Time-Points at Week 2, Week 6, and Month 3 | Mean change from baseline - Month 3 4PM | -7.31 mmHg | Standard Deviation 3.296 |
| Latanoprost 0.005% | Mean IOP Reduction From Time-Matched Baseline at the 8AM and 4PM Time-Points at Week 2, Week 6, and Month 3 | Mean change from baseline - Week 6 8AM | -9.33 mmHg | Standard Deviation 3.395 |
Secondary
Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population
Safety and tolerability based on number subjects with treatment emergent ocular adverse events.
Time frame: 3 months
Population: Safety population - all subjects who were randomized to treatment and received 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NCX 470 0.1% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any Ocular TEAEs | 13 numbers subjects with TEAEs |
| NCX 470 0.1% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any Non-Ocular TEAEs | 1 numbers subjects with TEAEs |
| NCX 470 0.1% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any serious Ocular TEAEs | 0 numbers subjects with TEAEs |
| NCX 470 0.1% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any serious Non-Ocular TEAEs | 0 numbers subjects with TEAEs |
| NCX 470 0.1% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any serious Ocular TEAEs related to study drug | 0 numbers subjects with TEAEs |
| NCX 470 0.1% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any serious Non-Ocular TEAEs related to study drug | 0 numbers subjects with TEAEs |
| Latanoprost 0.005% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any serious Non-Ocular TEAEs related to study drug | 0 numbers subjects with TEAEs |
| Latanoprost 0.005% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any Ocular TEAEs | 113 numbers subjects with TEAEs |
| Latanoprost 0.005% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any serious Non-Ocular TEAEs | 4 numbers subjects with TEAEs |
| Latanoprost 0.005% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any serious Ocular TEAEs related to study drug | 0 numbers subjects with TEAEs |
| Latanoprost 0.005% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any Non-Ocular TEAEs | 37 numbers subjects with TEAEs |
| Latanoprost 0.005% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any serious Ocular TEAEs | 0 numbers subjects with TEAEs |
| Latanoprost 0.005% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any Non-Ocular TEAEs | 32 numbers subjects with TEAEs |
| Latanoprost 0.005% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any serious Ocular TEAEs | 0 numbers subjects with TEAEs |
| Latanoprost 0.005% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any serious Non-Ocular TEAEs related to study drug | 0 numbers subjects with TEAEs |
| Latanoprost 0.005% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any serious Non-Ocular TEAEs | 3 numbers subjects with TEAEs |
| Latanoprost 0.005% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any Ocular TEAEs | 58 numbers subjects with TEAEs |
| Latanoprost 0.005% | Number of Subjects With Treatment Emergent Adverse Events (TEAE) by Treatment Group in the Safety Population | Any serious Ocular TEAEs related to study drug | 0 numbers subjects with TEAEs |
Secondary
Rate of Discontinuation
Number of subjects discontinued from the study.
Time frame: 3 months
Population: Subjects who were randomized to study drug and did not complete the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NCX 470 0.1% | Rate of Discontinuation | 3 Participants |
| Latanoprost 0.005% | Rate of Discontinuation | 14 Participants |
| Latanoprost 0.005% | Rate of Discontinuation | 17 Participants |
Secondary
Reduction From Baseline in Mean Diurnal IOP at Week 2, Week 6, and Month 3 in the Study Eye
Subjects in the NCX 470 0.065% treatment group were discontinued at Week 2 based upon the results of the planned, interim analysis. Subjects in the NCX 470 0.1% and Latanoprost 0.005% treatment groups continued for 3 months. Participants used medication in both eyes for 3 months with 1 eye designated as study eye at baseline. The study eye was defined as the eye with the highest mean diurnal intraocular pressure (IOP) value at baseline (or right eye if both eyes had the same IOP value at baseline).
Time frame: Baseline, Week 2, Week 6, and Month 3
Population: Participants used medication in both eyes for 3 months with 1 eye designated as study eye at baseline. The study eye was defined as the eye with the highest mean diurnal intraocular pressure (IOP) value at baseline (or right eye if both eyes had the same IOP value at baseline).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NCX 470 0.1% | Reduction From Baseline in Mean Diurnal IOP at Week 2, Week 6, and Month 3 in the Study Eye | Change from Baseline to Week 6 in Mean Diurnal IOP | -9.01 mmHg | Standard Deviation 2.758 |
| NCX 470 0.1% | Reduction From Baseline in Mean Diurnal IOP at Week 2, Week 6, and Month 3 in the Study Eye | Change from Baseline to Week 2 in Mean Diurnal IOP | -8.82 mmHg | Standard Deviation 3.057 |
| NCX 470 0.1% | Reduction From Baseline in Mean Diurnal IOP at Week 2, Week 6, and Month 3 in the Study Eye | Change from Baseline to Month 3 in Mean Diurnal IOP | -8.90 mmHg | Standard Deviation 2.697 |
| Latanoprost 0.005% | Reduction From Baseline in Mean Diurnal IOP at Week 2, Week 6, and Month 3 in the Study Eye | Change from Baseline to Week 2 in Mean Diurnal IOP | -8.05 mmHg | Standard Deviation 3.02 |
| Latanoprost 0.005% | Reduction From Baseline in Mean Diurnal IOP at Week 2, Week 6, and Month 3 in the Study Eye | Change from Baseline to Week 6 in Mean Diurnal IOP | -8.34 mmHg | Standard Deviation 3.03 |
| Latanoprost 0.005% | Reduction From Baseline in Mean Diurnal IOP at Week 2, Week 6, and Month 3 in the Study Eye | Change from Baseline to Month 3 in Mean Diurnal IOP | -8.41 mmHg | Standard Deviation 2.952 |