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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%.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NCX 470 0.065% | Experimental | NCX 470 Ophthalmic Solution, 0.065% dosed once daily to both eyes (initial phase of trial) |
|
| NCX 470 0.1% | Experimental | NCX 470 Ophthalmic Solution, 0.1% dosed once daily to both eyes (initial phase of trial) |
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| Latanoprost 0.005% | Active Comparator | Latanoprost Ophthalmic Solution, 0.005% dosed once daily to both eyes (initial phase of trial) |
|
| NCX 470 0.1% (remainder of trial) | Experimental | NCX 470 Ophthalmic Solution, 0.1% dosed once daily to both eyes (chosen dose of NCX 470 to continue in remainder of trial) |
|
| Latanoprost 0.005% (remainder of trial) | Active Comparator | Latanoprost Ophthalmic Solution, 0.005% dosed once daily to both eyes (active comparator for remainder of trial) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NCX 470 0.065% (initial phase of trial) | Drug | NCX 470 Ophthalmic Solution, 0.065% (initial phase of trial) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, Week 2, Week 6, and Month 3 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nicox Ophthalmics, Inc. | Nicox Ophthalmics, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Eye Research Foundation | Newport Beach | California | 92663 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39477206 | Derived | Mansberger SL, Fechtner R, Lopez K, Hubatsch D. A phase 3 adaptive dose selection trial of NCX 470, a nitric oxide-donating bimatoprost for open-angle glaucoma or ocular hypertension: The MONT BLANC study. Contemp Clin Trials. 2024 Dec;147:107730. doi: 10.1016/j.cct.2024.107730. Epub 2024 Oct 28. |
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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 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.
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| ID | Title | Description |
|---|---|---|
| FG000 | NCX 470 0.065% | NCX 470 Ophthalmic Solution, 0.065% dosed once daily to both eyes |
| FG001 | NCX 470 0.1% | NCX 470 Ophthalmic Solution, 0.1% dosed once daily to both eyes |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 8, 2020 | Sep 12, 2024 |
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double-masked
| Latanoprost 0.005% (initial phase of trial) | Drug | Latanoprost Ophthalmic Solution, 0.005% |
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|
| NCX 470 0.1% (initial phase of trial) | Drug | NCX 470 Ophthalmic Solution, 0.1% |
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| NCX 470 0.1% (remainder of trial) | Drug | NCX 470 Ophthalmic Solution, 0.1% |
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| Latanoprost 0.005% (remainder of trial) | Drug | Latanoprost Ophthalmic Solution, 0.005% |
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| Baseline, Week 2, Week 6, and Month 3 |
| 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. | 3 months |
| Rate of Discontinuation | Number of subjects discontinued from the study. | 3 months |
| FG002 | Latanoprost 0.005% | Latanoprost Ophthalmic Solution, 0.005% dosed once daily to both eyes |
| COMPLETED |
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| NOT COMPLETED |
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A study eye was assigned based upon the baseline IOP collected at the Eligibility Visits. The primary efficacy analysis was performed on the study eye and the fellow was followed for safety.
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| ID | Title | Description |
|---|---|---|
| BG000 | NCX 470 0.065% | NCX 470 Ophthalmic Solution, 0.065% dosed once daily to both eyes |
| BG001 | NCX 470 0.1% | NCX 470 Ophthalmic Solution, 0.1% dosed once daily to both eyes |
| BG002 | Latanoprost 0.005% | Latanoprost Ophthalmic Solution, 0.005% dosed once daily to both eyes |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Time-Matched IOP | Baseline time-matched IOP is the average of the IOP at Eligibility 1 and Eligibility 2 Visits (study eye) | Mean | Standard Deviation | mmHg |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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. | 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). | Posted | Mean | Standard Deviation | mmHg | Baseline, Week 2, Week 6, and Month 3 | eyes | eyes |
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| 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). | 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). | Posted | Mean | Standard Deviation | mmHg | Baseline, Week 2, Week 6, and Month 3 | eyes | eyes |
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| 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. | Safety population - all subjects who were randomized to treatment and received 1 dose of study medication. | Posted | Number | numbers subjects with TEAEs | 3 months |
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| Secondary | Rate of Discontinuation | Number of subjects discontinued from the study. | Subjects who were randomized to study drug and did not complete the study. | Posted | Count of Participants | Participants | 3 months |
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Adverse events were collected through 90 days of dosing of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | NCX 470 0.065% | NCX 470 Ophthalmic Solution, 0.065% dosed once daily to both eyes | 0 | 30 | 0 | 30 | 12 | 30 |
| EG001 | NCX 470 0.1% | NCX 470 Ophthalmic Solution, 0.1% dosed once daily to both eyes | 0 | 328 | 4 | 328 | 112 | 328 |
| EG002 | Latanoprost 0.005% | Latanoprost Ophthalmic Solution, 0.005% dosed once daily to both eyes | 2 | 333 | 3 | 333 | 32 | 333 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDra (v23.) | Non-systematic Assessment | Systemic event |
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| Sepsis | Infections and infestations | MedDra (v23.) | Non-systematic Assessment | Systemic event |
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| Cellulitis | Infections and infestations | MedDra (v23.) | Non-systematic Assessment | Systemic event |
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| Corona Virus Infection | Infections and infestations | MedDra (v23.) | Non-systematic Assessment | Systemic event |
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| Angina pectoris | Cardiac disorders | MedDra (v23.) | Non-systematic Assessment | Systemic event |
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| Transient ischemic attack | Nervous system disorders | MedDra (v23.) | Non-systematic Assessment | Systemic event |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Conjunctival hyperemia | Eye disorders | MedDra (v23.) | Systematic Assessment | Ocular event |
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| Ocular hyperemia | Eye disorders | MedDra (v23.) | Non-systematic Assessment | Ocular event |
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| Eye pruritus | Eye disorders | MedDra (v23.) | Non-systematic Assessment | Ocular event |
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| Instillation site pain | General disorders | MedDra (v23.) | Non-systematic Assessment | Ocular event |
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This was a robust, international trial demonstrating the safety and efficacy of NCX 470 0.1% Ophthalmic Solution. A 2nd Phase 3 trial is on-going and the sponsor expects the results of the 2nd trial to be consistent with the results of this study. While this study was only 3 months in length, the 2nd trial is a 12-month study.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Doug Hubatsch/Chief Scientific Officer | Nicox Ophthalmics, Inc. | 984-710-5354 | hubatsch@nicox.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 6, 2022 | Sep 12, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D005902 | Glaucoma, Open-Angle |
| D009798 | Ocular Hypertension |
| ID | Term |
|---|---|
| D005901 | Glaucoma |
| D005128 | Eye Diseases |
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| ID | Term |
|---|---|
| D000077338 | Latanoprost |
| ID | Term |
|---|---|
| D011461 | Prostaglandins F, Synthetic |
| D011465 | Prostaglandins, Synthetic |
| D011453 | Prostaglandins |
| D015777 | Eicosanoids |
| D005231 | Fatty Acids, Unsaturated |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D012898 | Autacoids |
| D018836 | Inflammation Mediators |
| D001685 | Biological Factors |
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| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| China |
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| Time-Matched IOP 4PM |
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| Mean change from baseline - Week 6 8AM |
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| Mean change from baseline - Week 6 4PM |
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| Mean change from baseline - Month 3 8AM |
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| Mean change from baseline - Month 3 4PM |
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Non-inferiority was concluded if the lower limit of the 95.1% CIs around the difference (NCX 470 minus latanoprost 0.005%) in mean IOP reduction from time-matched baseline in the study eye was greater than or equal to -1.5 mmHg at all time points and was greater than or equal to -1.0 mmHg at a majority of the time points. |
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