Ocular HypertensionPhase 1/2NCT02743780
A Three Part Study of MGV354 in Ocular Hypertension or Glaucoma
A Phase 1/2 study testing MGV354 ophthalmic suspension in people with Ocular Hypertension and Open-Angle Glaucoma, run by Alcon Research.
Trial summary
The purpose of this study is to determine if the clinical profile of topical-ocular MGV354 merits further development for the indication of lowering intraocular pressure (IOP). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Ocular Hypertension, Open-Angle Glaucoma
- What is being tested?
- MGV354 ophthalmic suspension
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 191 participants
- Where
- No sites listed yet
- Study dates
- 2 Mar 2016to 20 Sep 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Documented informed consent.
- Part 1: 18 to 70 years of age;
- Parts 2 and 3: 18 years of age or older;
- Able to communicate well with the investigator and understand and comply with the requirements of the study;
- Body Mass Index (BMI) between 18 and 39;
- In case of contact lens wear, willing to remove lenses 30 minutes before the first assessment until the end of the study. Corrective spectacles may be worn as needed.
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- Sitting vital signs (systolic and diastolic blood pressure and pulse rate) within normal ranges as specified in the protocol;
- Part 1 (Healthy Volunteers): In good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
- Parts 2 and 3 (Patients): Diagnosed with open-angle glaucoma or confirmed ocular hypertension; mean IOP measurements in at least one eye after washout as specified in the protocol
- Other protocol-specified inclusion criteria may apply.
Who cannot join
- History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes;
- History of or current presence of clinically significant ECG abnormalities or arrhythmias;
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical or breast cancer), treated or untreated, within the past 5 years;
- Known clinical history of heart failure, myocardial infarction, or stroke;
- Exposure during the four weeks preceding the Screening visit to any topical, inhaled, or systemic corticosteroids;
- Angle grade less than Grade 2 in either eye;
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- Any abnormality, including corneal thickness > 620 microns, preventing reliable applanation tonometry;
- Pregnant or lactating women and women of child-bearing potential;
- Sexually active males must agree to use a condom during intercourse while taking drug and for 6 days after stopping MGV354 medication and should not father a child in this period;
- Positive HIV, Hepatitis B Ag or Hepatitis C Ab test result at Screening;
- Abnormal liver function tests;
- History or presence of impaired renal function;
- Part 1 (Healthy Volunteers): Use of any NEW prescription drugs or herbal supplements within four (4) weeks prior to initial dosing, and/or NEW over-the-counter (OTC) medication, dietary supplements (vitamins included) within two (2) weeks prior to initial dosing.
- Parts 2 and 3 (Patients): Patients with related disease condition(s) including any form of glaucoma other than open-angle glaucoma and pseudoexfoliation and/or pigment dispersion components; patients who cannot safely discontinue use of all topical ocular and/or systemic IOP-lowering medication according to protocol-specified Washout Schedule; patients with ocular diseases or conditions as specified in the protocol; patients taking certain medications as specified in the protocol;
- Other protocol-specified exclusion criteria may apply.
About this study
Official title: A Three Part, First-in-human, Randomized, Double-masked, Placebo-Controlled, Safety, Tolerability and Early Efficacy Study of MGV354 in Healthy Subjects and in Patients With Ocular Hypertension or Glaucoma
The purpose of this study is to determine if the clinical profile of topical-ocular MGV354 merits further development for the indication of lowering intraocular pressure (IOP).
Read the detailed description
Part 1 will evaluate the safety and tolerability of single ascending doses of MGV354 compared to placebo in healthy male and female subjects. Part 2 will evaluate the safety and tolerability of MGV354 in a multiple ascending dose design (two highest tolerated doses from Part 1) compared to placebo when administered for 7 days to patients with ocular hypertension or glaucoma. Part 3 will explore the safety, tolerability and efficacy of a single dose level of MGV354 (maximum tolerated dose) compared to placebo when administered for 7 days in patients with ocular hypertension or glaucoma.
- Conditions
- Ocular Hypertension, Open-Angle Glaucoma
- Being tested
- MGV354 ophthalmic suspension, MGV354 placebo
- Keywords
- Ocular Hypertension, Open-Angle Glaucoma, POAG, Glaucoma
- Medical subject headings
- Ocular Hypertension, Glaucoma, Open-Angle, Glaucoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MGV354 ophthalmic suspensionDrug
MGV354 placeboDrug
Inactive ingredients used as placebo comparator
| Study group | Role | What they receive |
|---|---|---|
| MGV354 | Experimental | Part 3: MGV354 ophthalmic suspension, 1 drop in both eyes once per day for 7 days Receives: Drug: MGV354 ophthalmic suspension |
| Placebo | Placebo comparator | Part 3: MGV354 placebo, 1 drop in both eyes once per day for 7 days Receives: Drug: MGV354 placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 3: Change in Diurnal IOP (Averaged Over 8 AM, 10 AM, Noon, 4 PM, and 8 PM) From Baseline to Day 8
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Diurnal IOP was defined as the average of the five time points measured (8 AM, 10 AM, noon, 4 PM, and 8 PM). Baseline diurnal IOP was the average of IOP measurements obtained at the 2 eligibility visits. Change from baseline was calculated by taking the change at each time point from baseline to Day 8 and averaging the available changes. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) contributed to the analysis.
Measured: Baseline, Day 8
Part 3: Change in IOP From Baseline to Day 8 at 8 AM, 10 AM, Noon, 4 PM, and 8 PM
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Baseline IOP was the average of IOP measurements obtained at the 2 eligibility visits. Change from baseline was calculated by taking the change at each time point from baseline to Day 8. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) contributed to the analysis.
Measured: Baseline, Day 8
Secondary outcomes (12)
Part 3: Change From Baseline in IOP at 36 Hours and 48 Hours Post Day 7 Administration
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Baseline IOP was the average of IOP measurements obtained at the 2 eligibility visits. Change from baseline was calculated by taking the change at each time point from baseline to Day 8 and averaging the available changes. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) contributed to the analysis.
Measured: Baseline, up to Day 9
Part 1: Maximum Observed Concentration [Cmax (ng/mL)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point. Cmax is reported as mass/volume.
Measured: Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose
Part 1: Time to Reach Maximum Concentration [Tmax (h)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point.
Measured: Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUClast (ng*h/mL)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point. AUClast is reported as mass*time/volume.
Measured: Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to 120 Hours Post Dose [AUC0-120 (ng*h/mL)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was to be collected at each time point.
Measured: Pre-dose to 120 hours post-dose
Part 1: Area Under the Concentration-time Curve From 0 to Infinity [AUCinf (ng*h/mL)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was to be collected at each time point.
Measured: Pre-dose to 120 hours post-dose
Part 1: Terminal Elimination Half-life [t1/2 (h)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was to be collected at each time point.
Measured: Pre-dose to 120 hours post-dose
Part 2: Maximum Observed Concentration [Cmax (ng/mL)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point. Cmax is reported as mass/volume.
Measured: Up to Day 7
Part 2: Time to Reach Maximum Concentration [Tmax (h)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point.
Measured: Up to Day 7
Part 2: Area Under the Concentration-time Curve From 0 to the End of the Dosing Interval Tau [AUCtau (ng*h/mL)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point. AUCtau is reported as mass*time/volume.
Measured: Up to Day 7
Part 2: Accumulation Ratio (Racc)
Accumulation Ratio was derived using Cmax on Day 7 versus Cmax on Day 1. Approximately 2 mL of venous blood was collected at each time point.
Measured: Day 7
Part 3: Observed Concentration at 12 Hours Following Drug Administration [C12 (ng/mL)]
Based on plasma samples collected at pre-determined nominal time points, dependent on observed concentrations. Approximately 2 mL of venous blood was collected at each time point. C12 is reported as mass/volume.
Measured: Up to Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2016 (estimated)
- Study start2 Mar 2016
- Primary completion20 Sep 2016
- Study completion20 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ocular HypertensionStudies of the same condition, open and under way.
- More trials run by Alcon ResearchThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 191 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alcon Research
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Novartis Institutes for BioMedical Research
- Responsible party
- Sponsor
- Investigators
- Clinical Science Expert, NIBR, Study director, Novartis Institutes for BioMedical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02743780
- Sponsor's protocol ID
- MGV354-2201
- Status last verified
- Aug 2017
- First submitted
- 14 Apr 2016
- Last updated
- 2 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Stacy R, Huttner K, Watts J, Peace J, Wirta D, Walters T, Sall K, Seaman J, Ni X, Prasanna G, Mogi M, Adams C, Yan JH, Wald M, He Y, Newton R, Kolega R, Grosskreutz C. A Randomized, Controlled Phase I/II Study to Evaluate the Safety and Efficacy of MGV354 for Ocular Hypertension or Glaucoma. Am J Ophthalmol. 2018 Aug;192:113-123. doi: 10.1016/j.ajo.2018.05.015. Epub 2018 May 24.
PubMed 29802818
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Three Part, First-in-human, Randomized, Double-masked, Placebo-Controlled, Safety, Tolerability and Early Efficacy Study of MGV354 in Healthy Subjects and in Patients With Ocular Hypertension or Glaucoma
- ClinicalTrials.gov ID
- NCT02743780
- Acronym / sponsor ID
- MGV354-2201
- Conditions
- Ocular Hypertension, Open-Angle Glaucoma
- Keywords
- Ocular Hypertension, Open-Angle Glaucoma, POAG, Glaucoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 191 participants (actual)
- Lead sponsor
- Alcon ResearchIndustry (pharma, biotech, devices)
- Collaborators
- Novartis Institutes for BioMedical Research
- Study start
- 2 Mar 2016 (actual)
- Primary completion
- 20 Sep 2016 (actual)
- Study completion
- 20 Sep 2016 (actual)
- First posted
- 19 Apr 2016 (estimated)
- Results
- Posted 31 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if the clinical profile of topical-ocular MGV354 merits further development for the indication of lowering intraocular pressure (IOP).
Detailed description
Part 1 will evaluate the safety and tolerability of single ascending doses of MGV354 compared to placebo in healthy male and female subjects. Part 2 will evaluate the safety and tolerability of MGV354 in a multiple ascending dose design (two highest tolerated doses from Part 1) compared to placebo when administered for 7 days to patients with ocular hypertension or glaucoma. Part 3 will explore the safety, tolerability and efficacy of a single dose level of MGV354 (maximum tolerated dose) compared to placebo when administered for 7 days in patients with ocular hypertension or glaucoma.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MGV354 | Experimental | Drug: MGV354 ophthalmic suspensionPart 3: MGV354 ophthalmic suspension, 1 drop in both eyes once per day for 7 days |
| Placebo | Placebo comparator | Drug: MGV354 placeboPart 3: MGV354 placebo, 1 drop in both eyes once per day for 7 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Documented informed consent.
- Part 1: 18 to 70 years of age;
- Parts 2 and 3: 18 years of age or older;
- Able to communicate well with the investigator and understand and comply with the requirements of the study;
- Body Mass Index (BMI) between 18 and 39;
Key exclusion criteria (15 listed)
- History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes;
- History of or current presence of clinically significant ECG abnormalities or arrhythmias;
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical or breast cancer), treated or untreated, within the past 5 years;
- Known clinical history of heart failure, myocardial infarction, or stroke;
- Exposure during the four weeks preceding the Screening visit to any topical, inhaled, or systemic corticosteroids;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MGV354 ophthalmic suspension | Drug | MGV354 |
| MGV354 placeboInactive ingredients used as placebo comparator | Drug | Placebo |
Primary outcome
Part 3: Change in Diurnal IOP (Averaged Over 8 AM, 10 AM, Noon, 4 PM, and 8 PM) From Baseline to Day 8
Time frame: Baseline, Day 8
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Diurnal IOP was defined as the average of the five time points measured (8 AM, 10 AM, noon, 4 PM, and 8 PM). Baseline diurnal IOP was the average of IOP measurements obtained at the 2 eligibility visits. Change from baseline was calculated by taking the change at each time point from baseline to Day 8 and averaging the available changes. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) contributed to the analysis.
Part 3: Change in IOP From Baseline to Day 8 at 8 AM, 10 AM, Noon, 4 PM, and 8 PM
Time frame: Baseline, Day 8
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Baseline IOP was the average of IOP measurements obtained at the 2 eligibility visits. Change from baseline was calculated by taking the change at each time point from baseline to Day 8. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) contributed to the analysis.
12 secondary outcomes
Part 3: Change From Baseline in IOP at 36 Hours and 48 Hours Post Day 7 Administration
Time frame: Baseline, up to Day 9
Part 1: Maximum Observed Concentration [Cmax (ng/mL)]
Time frame: Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose
Part 1: Time to Reach Maximum Concentration [Tmax (h)]
Time frame: Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUClast (ng*h/mL)]
Time frame: Pre-dose, .5, 2, 4, 6, 12, 24, 48, 72, 96, 120 hours post-dose, and Day 7 post-dose
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero to 120 Hours Post Dose [AUC0-120 (ng*h/mL)]
Time frame: Pre-dose to 120 hours post-dose
Part 1: Area Under the Concentration-time Curve From 0 to Infinity [AUCinf (ng*h/mL)]
Time frame: Pre-dose to 120 hours post-dose
Part 1: Terminal Elimination Half-life [t1/2 (h)]
Time frame: Pre-dose to 120 hours post-dose
Part 2: Maximum Observed Concentration [Cmax (ng/mL)]
Time frame: Up to Day 7
Part 2: Time to Reach Maximum Concentration [Tmax (h)]
Time frame: Up to Day 7
Part 2: Area Under the Concentration-time Curve From 0 to the End of the Dosing Interval Tau [AUCtau (ng*h/mL)]
Time frame: Up to Day 7
Part 2: Accumulation Ratio (Racc)
Time frame: Day 7
Part 3: Observed Concentration at 12 Hours Following Drug Administration [C12 (ng/mL)]
Time frame: Up to Day 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29802818Stacy R, Huttner K, Watts J, Peace J, Wirta D, Walters T, Sall K, Seaman J, Ni X, Prasanna G, Mogi M, Adams C, Yan JH, Wald M, He Y, Newton R, Kolega R, Grosskreutz C. A Randomized, Controlled Phase I/II Study to Evaluate the Safety and Efficacy of MGV354 for Ocular Hypertension or Glaucoma. Am J Ophthalmol. 2018 Aug;192:113-123. doi: 10.1016/j.ajo.2018.05.015. Epub 2018 May 24.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Science Expert, NIBR study director
Novartis Institutes for BioMedical Research
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MGV354 ophthalmic suspension in people with Ocular Hypertension and Open-Angle Glaucoma, run by Alcon Research.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 3: Change in Diurnal IOP (Averaged Over 8 AM, 10 AM, Noon, 4 PM, and 8 PM) From Baseline to Day 8 (time frame: Baseline, Day 8). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02743780, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2018.