Trial Outcomes & Findings for Study of MP0112 Intravitreal Injection in Patients With Wet Age Related Macular Degeneration (NCT NCT01086761)
NCT ID: NCT01086761
Last Updated: 2014-05-12
Results Overview
MTD was defined as one dose level below the lower of the dose level in which a severe (sight-threatening) drug-related Adverse Event occurred or the dose level at which more than 2 patients experienced a moderate ocular (eye) drug-related toxicity.
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
32 participants
Primary outcome timeframe
16 weeks
Results posted on
2014-05-12
Participant Flow
Participant milestones
| Measure |
MP0112 (0.04 mg)
Single 0.04 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (0.15 mg)
Single 0.15 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (0.4 mg)
Single 0.4 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (1.0 mg)
Single 1.0 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (2.0 mg)
Single 2.0 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (3.6 mg)
Single 3.6 mg intravitreal injection of MP0112 in the study eye.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
9
|
7
|
6
|
6
|
4
|
0
|
|
Overall Study
COMPLETED
|
9
|
7
|
6
|
6
|
4
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of MP0112 Intravitreal Injection in Patients With Wet Age Related Macular Degeneration
Baseline characteristics by cohort
| Measure |
MP0112 (0.04 mg)
n=9 Participants
Single 0.04 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (0.15 mg)
n=7 Participants
Single 0.15 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (0.4 mg)
n=6 Participants
Single 0.4 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (1.0 mg)
n=6 Participants
Single 1.0 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (2.0 mg)
n=4 Participants
Single 2.0 mg intravitreal injection of MP0112 in the study eye.
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
78.2 Years
STANDARD_DEVIATION 6.3 • n=5 Participants
|
78.6 Years
STANDARD_DEVIATION 3.2 • n=7 Participants
|
77.5 Years
STANDARD_DEVIATION 6.0 • n=5 Participants
|
79.0 Years
STANDARD_DEVIATION 3.0 • n=4 Participants
|
77.8 Years
STANDARD_DEVIATION 9.4 • n=21 Participants
|
78.3 Years
STANDARD_DEVIATION 5.3 • n=8 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
21 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
11 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 16 weeksPopulation: All treated participants.
MTD was defined as one dose level below the lower of the dose level in which a severe (sight-threatening) drug-related Adverse Event occurred or the dose level at which more than 2 patients experienced a moderate ocular (eye) drug-related toxicity.
Outcome measures
| Measure |
MP0112
n=32 Participants
Single intravitreal injection of MP0112 in the study eye of one of the following doses: 0.04 mg, 0.15 mg, 0.4 mg, 1.0 mg or 2.0 mg.
|
MP0112 (0.15 mg)
Single 0.15 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (0.4 mg)
Single 0.4 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (1.0 mg)
Single 1.0 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (2.0 mg)
Single 2.0 mg intravitreal injection of MP0112 in the study eye.
|
|---|---|---|---|---|---|
|
Maximal Tolerated Dose (MTD) Following a Single Injection
|
1.0 mg
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 4Population: All treated participants.
BCVA was measured using an eye chart and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye at Baseline and Week 4. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The higher the letters read correctly on the eye chart the better the vision. Stable or Improved BCVA was defined as a loss of \<15 letters read correctly compared to Baseline.
Outcome measures
| Measure |
MP0112
n=9 Participants
Single intravitreal injection of MP0112 in the study eye of one of the following doses: 0.04 mg, 0.15 mg, 0.4 mg, 1.0 mg or 2.0 mg.
|
MP0112 (0.15 mg)
n=7 Participants
Single 0.15 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (0.4 mg)
n=6 Participants
Single 0.4 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (1.0 mg)
n=6 Participants
Single 1.0 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (2.0 mg)
n=4 Participants
Single 2.0 mg intravitreal injection of MP0112 in the study eye.
|
|---|---|---|---|---|---|
|
Percentage of Participants With Stable or Improved Best Corrected Visual Acuity (BCVA)
|
100 Percentage of participants
|
100 Percentage of participants
|
100 Percentage of participants
|
83 Percentage of participants
|
75 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, Week 4Population: All treated participants.
Optical Coherence Tomography (OCT), a laser based non-invasive diagnostic system providing high-resolution imaging sections of the retina, was performed in the study eye after pupil dilation at Baseline and Week 4. A negative change from Baseline indicated improvement (less retinal thickness). A positive change from Baseline indicated worsening (definite retinal thickening).
Outcome measures
| Measure |
MP0112
n=9 Participants
Single intravitreal injection of MP0112 in the study eye of one of the following doses: 0.04 mg, 0.15 mg, 0.4 mg, 1.0 mg or 2.0 mg.
|
MP0112 (0.15 mg)
n=7 Participants
Single 0.15 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (0.4 mg)
n=6 Participants
Single 0.4 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (1.0 mg)
n=6 Participants
Single 1.0 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (2.0 mg)
n=4 Participants
Single 2.0 mg intravitreal injection of MP0112 in the study eye.
|
|---|---|---|---|---|---|
|
Change From Baseline in Central Area Retinal Thickness
Baseline
|
353.0 μm
Standard Deviation 79.3
|
338.0 μm
Standard Deviation 69.7
|
367.2 μm
Standard Deviation 213.5
|
333.3 μm
Standard Deviation 79.4
|
375.3 μm
Standard Deviation 69.3
|
|
Change From Baseline in Central Area Retinal Thickness
Change from Baseline at Week 4
|
21.6 μm
Standard Deviation 118.2
|
10.1 μm
Standard Deviation 102.8
|
-39.8 μm
Standard Deviation 72.4
|
-95.0 μm
Standard Deviation 91.2
|
-99.0 μm
Standard Deviation 35.5
|
SECONDARY outcome
Timeframe: Baseline, Week 4Population: All treated participants.
Fluorescein angiography (FA) is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. FA was performed on the dilated study eye 10 minutes after fluorescein application at Baseline and Week 4. A lower number indicated a smaller area of leakage.
Outcome measures
| Measure |
MP0112
n=9 Participants
Single intravitreal injection of MP0112 in the study eye of one of the following doses: 0.04 mg, 0.15 mg, 0.4 mg, 1.0 mg or 2.0 mg.
|
MP0112 (0.15 mg)
n=7 Participants
Single 0.15 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (0.4 mg)
n=6 Participants
Single 0.4 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (1.0 mg)
n=6 Participants
Single 1.0 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (2.0 mg)
n=4 Participants
Single 2.0 mg intravitreal injection of MP0112 in the study eye.
|
|---|---|---|---|---|---|
|
Area of Leakage as Measured by Fluorescein Angiography
Week 4 (n=9,7,6,6,3)
|
4.1 mm^2
Standard Deviation 4.9
|
2.6 mm^2
Standard Deviation 3.5
|
2.4 mm^2
Standard Deviation 3.8
|
1.0 mm^2
Standard Deviation 2.4
|
0.0 mm^2
Standard Deviation 0.0
|
|
Area of Leakage as Measured by Fluorescein Angiography
Baseline
|
15.0 mm^2
Standard Deviation 4.0
|
9.5 mm^2
Standard Deviation 3.0
|
12.8 mm^2
Standard Deviation 5.9
|
8.4 mm^2
Standard Deviation 4.0
|
10.2 mm^2
Standard Deviation 7.5
|
SECONDARY outcome
Timeframe: Baseline, Week 4Population: All treated participants with data available for analysis.
Fluorescein angiography (FA) is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. FA was performed on the dilated study eye after fluorescein application at Baseline and Week 4. A lower number indicated a smaller lesion area.
Outcome measures
| Measure |
MP0112
n=9 Participants
Single intravitreal injection of MP0112 in the study eye of one of the following doses: 0.04 mg, 0.15 mg, 0.4 mg, 1.0 mg or 2.0 mg.
|
MP0112 (0.15 mg)
n=7 Participants
Single 0.15 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (0.4 mg)
n=6 Participants
Single 0.4 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (1.0 mg)
n=6 Participants
Single 1.0 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (2.0 mg)
n=4 Participants
Single 2.0 mg intravitreal injection of MP0112 in the study eye.
|
|---|---|---|---|---|---|
|
Area of Lesion as Measured by Fluorescein Angiography
Baseline
|
13.9 mm^2
Standard Deviation 3.9
|
8.0 mm^2
Standard Deviation 3.6
|
12.1 mm^2
Standard Deviation 6.9
|
9.5 mm^2
Standard Deviation 4.4
|
10.9 mm^2
Standard Deviation 7.9
|
|
Area of Lesion as Measured by Fluorescein Angiography
Week 4 (n=9,6,6,6,2)
|
8.3 mm^2
Standard Deviation 4.8
|
6.2 mm^2
Standard Deviation 3.9
|
6.8 mm^2
Standard Deviation 4.1
|
7.3 mm^2
Standard Deviation 4.6
|
11.7 mm^2
Standard Deviation 6.1
|
SECONDARY outcome
Timeframe: Day 3Population: Pharmacokinetic (PK) Population included all treated participants with PK data.
Blood samples were collected for MP0112 levels on Day 3. The serum samples (liquid portion of the blood after cells and clotting factors were removed) were sent to a laboratory and were analyzed for MP0112 levels using an enzyme-linked immunosorbent assay. Maximum concentration at Day 3 was calculated.
Outcome measures
| Measure |
MP0112
n=9 Participants
Single intravitreal injection of MP0112 in the study eye of one of the following doses: 0.04 mg, 0.15 mg, 0.4 mg, 1.0 mg or 2.0 mg.
|
MP0112 (0.15 mg)
n=7 Participants
Single 0.15 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (0.4 mg)
n=6 Participants
Single 0.4 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (1.0 mg)
n=6 Participants
Single 1.0 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (2.0 mg)
n=4 Participants
Single 2.0 mg intravitreal injection of MP0112 in the study eye.
|
|---|---|---|---|---|---|
|
Maximum Serum Concentration (Cmax) of MP0112 at Day 3
|
NA Nanomolar (nM)
NA
Result is below the lower limit of quantitation of the laboratory test: \<0.3 nM.
|
NA Nanomolar (nM)
NA
Result is below the lower limit of quantitation of the laboratory test: \<0.3 nM.
|
NA Nanomolar (nM)
NA
Result is below the lower limit of quantitation of the laboratory test: \<0.3 nM.
|
0.5 Nanomolar (nM)
|
1.0 Nanomolar (nM)
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: Safety Population included all treated participants.
Blood samples were collected Pre-treatment (Baseline) and Weeks 4, 8 and 12. Samples were analyzed for Anti-MP0112 antibodies using an enzyme-linked immunosorbent assay.
Outcome measures
| Measure |
MP0112
n=9 Participants
Single intravitreal injection of MP0112 in the study eye of one of the following doses: 0.04 mg, 0.15 mg, 0.4 mg, 1.0 mg or 2.0 mg.
|
MP0112 (0.15 mg)
n=7 Participants
Single 0.15 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (0.4 mg)
n=6 Participants
Single 0.4 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (1.0 mg)
n=6 Participants
Single 1.0 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (2.0 mg)
n=4 Participants
Single 2.0 mg intravitreal injection of MP0112 in the study eye.
|
|---|---|---|---|---|---|
|
Number of Participants With Positive Binding Anti-MP0112 Antibodies
|
0 Participants
|
1 Participants
|
3 Participants
|
1 Participants
|
3 Participants
|
Adverse Events
MP0112 (0.04 mg)
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
MP0112 (0.15 mg)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
MP0112 (0.4 mg)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
MP0112 (1.0 mg)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
MP0112 (2.0 mg)
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
MP0112 (0.04 mg)
n=9 participants at risk
Single 0.04 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (0.15 mg)
n=7 participants at risk
Single 0.15 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (0.4 mg)
n=6 participants at risk
Single 0.4 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (1.0 mg)
n=6 participants at risk
Single 1.0 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (2.0 mg)
n=4 participants at risk
Single 2.0 mg intravitreal injection of MP0112 in the study eye.
|
|---|---|---|---|---|---|
|
Infections and infestations
Endophthalmitis
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/6
|
25.0%
1/4
|
Other adverse events
| Measure |
MP0112 (0.04 mg)
n=9 participants at risk
Single 0.04 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (0.15 mg)
n=7 participants at risk
Single 0.15 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (0.4 mg)
n=6 participants at risk
Single 0.4 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (1.0 mg)
n=6 participants at risk
Single 1.0 mg intravitreal injection of MP0112 in the study eye.
|
MP0112 (2.0 mg)
n=4 participants at risk
Single 2.0 mg intravitreal injection of MP0112 in the study eye.
|
|---|---|---|---|---|---|
|
Cardiac disorders
Ventricular fibrillation
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
|
Eye disorders
Macular degeneration
|
77.8%
7/9
|
100.0%
7/7
|
83.3%
5/6
|
33.3%
2/6
|
50.0%
2/4
|
|
Eye disorders
Anterior chamber inflammation
|
0.00%
0/9
|
14.3%
1/7
|
16.7%
1/6
|
33.3%
2/6
|
25.0%
1/4
|
|
Eye disorders
Anterior chamber cell
|
0.00%
0/9
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
50.0%
2/4
|
|
Eye disorders
Cataract
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/4
|
|
Eye disorders
Conjunctival haemorrhage
|
0.00%
0/9
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/4
|
|
Eye disorders
Corneal epithelium defect
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/6
|
25.0%
1/4
|
|
Eye disorders
Detachment of retinal pigment epithelium
|
0.00%
0/9
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/4
|
|
Eye disorders
Eye pain
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/4
|
|
Eye disorders
Iridocyclitis
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/4
|
|
Eye disorders
Macular cyst
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
|
Eye disorders
Macular oedema
|
0.00%
0/9
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/4
|
|
Eye disorders
Ocular toxicity
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/6
|
25.0%
1/4
|
|
Eye disorders
Pseudoendophthalmitis
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/6
|
25.0%
1/4
|
|
Eye disorders
Retinal haemorrhage
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/6
|
25.0%
1/4
|
|
Eye disorders
Retinal neovascularisation
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/6
|
25.0%
1/4
|
|
Eye disorders
Retinal oedema
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
|
Eye disorders
Subretinal fibrosis
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
|
Eye disorders
Uveitis
|
0.00%
0/9
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/4
|
|
Eye disorders
Vitreal cells
|
0.00%
0/9
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/4
|
|
Eye disorders
Vitreous detachment
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/4
|
|
Eye disorders
Vitreous opacities
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/4
|
|
General disorders
Chest pain
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/6
|
25.0%
1/4
|
|
Infections and infestations
Bronchitis
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
|
Infections and infestations
Urinary tract infection
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
|
Investigations
Blood pressure increased
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/4
|
|
Investigations
Intraocular pressure decreased
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
|
Psychiatric disorders
Anxiety
|
11.1%
1/9
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/4
|
|
Vascular disorders
Hypertension
|
0.00%
0/9
|
0.00%
0/7
|
16.7%
1/6
|
16.7%
1/6
|
0.00%
0/4
|
|
Eye disorders
Vitritis
|
0.00%
0/9
|
14.3%
1/7
|
0.00%
0/6
|
33.3%
2/6
|
25.0%
1/4
|
|
Infections and infestations
Endophthalmitis
|
0.00%
0/9
|
0.00%
0/7
|
0.00%
0/6
|
0.00%
0/6
|
25.0%
1/4
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER