Trial Outcomes & Findings for Study to Evaluate Safety, Tolerability & PK of rhNGF in Healthy Volunteers (NCT NCT03836859)
NCT ID: NCT03836859
Last Updated: 2023-12-26
Results Overview
Change from baseline in VAS ocular tolerability score in study eye at Day 2 8h, Day 3 predose, Day 6 pre-dose, Day 6 8h, Day 7 (FU1), Day 8 (FU2), Day 16 (FU3) (Tolerability of 6x0.70 μg rhNGF per day) for overall is presented. In this context, "Baseline" was defined as the pre-treatment assessment at the Baseline (D-1) visit.A ocular tolerability score was determined using a 100 mm VAS on which 0 meant No symptoms and 100 meant the Worst possible discomfort. The patients subjectively evaluated their ocular symptoms (foreign body sensation, burning or stinging, itching, pain, sticky feeling, blurred vision and photophobia) using the VAS giving the value they were feeling from none to an extreme value. The ocular symptoms were evaluated by the patients through the scale.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
at Day 2 8h, Day 3 predose, Day 6 pre-dose, Day 6 8h, Day 7 (FU1), Day 8 (FU2), Day 16 (FU3)
Results posted on
2023-12-26
Participant Flow
Participant milestones
| Measure |
rhNGF 20μg/mL
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Overall Study
STARTED
|
20
|
10
|
|
Overall Study
COMPLETED
|
20
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Evaluate Safety, Tolerability & PK of rhNGF in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
rhNGF 20μg/mL
n=20 Participants
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 Participants
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
20 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
40.5 years
STANDARD_DEVIATION 10.82 • n=5 Participants
|
33.1 years
STANDARD_DEVIATION 9.69 • n=7 Participants
|
38.0 years
STANDARD_DEVIATION 10.87 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
20 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=5 Participants
|
10 participants
n=7 Participants
|
30 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: On Day 1 (single dose scheme), Days 2-6 (multiple dose scheme), Day 7 (Follow-up [FU] 1), Day 8 (FU 2); Day 16 (FU 3), and Day 35-42 (FU 4)Population: The safety population is represented by randomized subjects who received a dose of study medication in at least one eye. All 30 randomized subjects were included in the Safety population.
TEAEs were defined as an adverse event (AE), which started after the first dose of study treatment. These comprise AEs during the treatment and follow-up period. For TEAE the number of events was provided.
Outcome measures
| Measure |
rhNGF 20μg/mL
n=20 Participants
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 Participants
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Number of Treatment Emergent Adverse Events (TEAEs).
|
27 events
|
9 events
|
PRIMARY outcome
Timeframe: During first dose schedule (TEAE Dose 1, which started after first dose of study treatment at Day 1 till before administration of the first dose at Treatment Day 2)Population: The safety population is represented by randomized subjects who received a dose of study medication in at least one eye. All 30 randomized subjects were included in the Safety population.
TEAEs Dose 1 were defined as TEAEs, which started after the first dose of study treatment and before administration of the first dose at Treatment Day 2. For TEAE the number of events was provided.
Outcome measures
| Measure |
rhNGF 20μg/mL
n=20 Participants
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 Participants
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Number of Treatment Emergent Adverse Events During First Dose Schedule (TEAEs Dose 1).
|
3 events
|
2 events
|
PRIMARY outcome
Timeframe: During second dose schedule (TEAE Dose 2, which started on/after the first dose at Treatment Day 2 till before Follow-Up Day 7 (FU1) visitPopulation: The safety population is represented by randomized subjects who received a dose of study medication in at least one eye. All 30 randomized subjects were included in the Safety population.
TEAEs Dose 2 were defined as TEAEs, which started on/after the first dose at Treatment Day 2 and before Follow-Up Day 7 visit.
Outcome measures
| Measure |
rhNGF 20μg/mL
n=20 Participants
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 Participants
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Number of Treatment Emergent Adverse Events During Second Dose Schedule (TEAEs Dose 2).
|
16 events
|
4 events
|
PRIMARY outcome
Timeframe: at Treatment Day 2 pre-doseChange from baseline in VAS ocular tolerability score in study eye at Treatment Day 2 predose (Tolerability of 1x0.70 μg rhNGF per day) for overall is presented. In this context, "Baseline" was defined as the pre-treatment assessment at the Baseline (D-1) visit. A ocular tolerability score was determined using a 100 mm VAS on which 0 meant No symptoms and 100 meant the Worst possible discomfort. The patients subjectively evaluated their ocular symptoms (foreign body sensation, burning or stinging, itching, pain, sticky feeling, blurred vision and photophobia) using the VAS giving the value they were feeling from none to an extreme value. The ocular symptoms were evaluated by the patients through the scale.
Outcome measures
| Measure |
rhNGF 20μg/mL
n=20 Participants
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 Participants
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score in Study Eye: Single Dose
|
0.36 score on a scale
Standard Deviation 1.325
|
0.24 score on a scale
Standard Deviation 0.410
|
PRIMARY outcome
Timeframe: at Day 2 8h, Day 3 predose, Day 6 pre-dose, Day 6 8h, Day 7 (FU1), Day 8 (FU2), Day 16 (FU3)Population: The safety population is represented by randomized subjects who received a dose of study medication in at least one eye. All 30 randomized subjects were included in the Safety population.
Change from baseline in VAS ocular tolerability score in study eye at Day 2 8h, Day 3 predose, Day 6 pre-dose, Day 6 8h, Day 7 (FU1), Day 8 (FU2), Day 16 (FU3) (Tolerability of 6x0.70 μg rhNGF per day) for overall is presented. In this context, "Baseline" was defined as the pre-treatment assessment at the Baseline (D-1) visit.A ocular tolerability score was determined using a 100 mm VAS on which 0 meant No symptoms and 100 meant the Worst possible discomfort. The patients subjectively evaluated their ocular symptoms (foreign body sensation, burning or stinging, itching, pain, sticky feeling, blurred vision and photophobia) using the VAS giving the value they were feeling from none to an extreme value. The ocular symptoms were evaluated by the patients through the scale.
Outcome measures
| Measure |
rhNGF 20μg/mL
n=20 Participants
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 Participants
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score in Study Eye: Multiple Dose
Day 2 - 8h
|
0.14 score on a scale
Standard Deviation 0.882
|
-0.09 score on a scale
Standard Deviation 0.376
|
|
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score in Study Eye: Multiple Dose
Day 3 - predose
|
0.47 score on a scale
Standard Deviation 0.673
|
0.14 score on a scale
Standard Deviation 0.559
|
|
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score in Study Eye: Multiple Dose
Day 6 - predose
|
1.60 score on a scale
Standard Deviation 5.091
|
0.17 score on a scale
Standard Deviation 0.740
|
|
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score in Study Eye: Multiple Dose
Day 6 - 8h
|
1.85 score on a scale
Standard Deviation 2.781
|
-0.06 score on a scale
Standard Deviation 0.358
|
|
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score in Study Eye: Multiple Dose
FUI1 - 0h
|
0.66 score on a scale
Standard Deviation 3.828
|
-0.13 score on a scale
Standard Deviation 0.353
|
|
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score in Study Eye: Multiple Dose
FUI2 - 8h
|
0.40 score on a scale
Standard Deviation 4.035
|
-0.30 score on a scale
Standard Deviation 0.474
|
|
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score in Study Eye: Multiple Dose
FUI3 - 0h
|
-0.23 score on a scale
Standard Deviation 1.470
|
-0.01 score on a scale
Standard Deviation 0.389
|
SECONDARY outcome
Timeframe: on or after Follow-Up Day 7 (FU1)Population: The safety population is represented by randomized subjects who received a dose of study medication in at least one eye. All 30 randomized subjects were included in the Safety population.
Follow-Up AEs (FUAE) were defined as TEAEs which start on or after Follow-Up Day 7 (FU1) visit
Outcome measures
| Measure |
rhNGF 20μg/mL
n=20 Participants
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 Participants
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Number of Follow-Up AEs (FUAE)
|
8 events
|
3 events
|
SECONDARY outcome
Timeframe: On Day 1 (single dose scheme), Days 2-6 (multiple dose scheme), Day 7 (Follow-up [FU] 1), Day 8 (FU 2); Day 16 (FU 3), and Day 35-42 (FU 4)Population: The safety population is represented by randomized subjects who received a dose of study medication in at least one eye. All 30 randomized subjects were included in the Safety population.
Ocular TEAEs were defined as an adverse event (AE) interesting the study or the non-study eye, which started after the first dose of study treatment. These comprise ocular AEs during the treatment and follow-up period. For these AE, the number of events was provided for the study eye and the non-study eye, separately.
Outcome measures
| Measure |
rhNGF 20μg/mL
n=20 Participants
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 Participants
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Number of Ocular TEAEs by Eyes
study eye
|
17 events
|
4 events
|
|
Number of Ocular TEAEs by Eyes
non-study eye
|
10 events
|
4 events
|
SECONDARY outcome
Timeframe: on Day -1 and at Day 8 (Follow up [FU] 2) and Day 16 (FU3)Population: The safety population is represented by randomized subjects who received a dose of study medication in at least one eye. All 30 randomized subjects were included in the Safety population
IOP was performed using either Goldmann applanation tonometry after the instillation of a topical anaesthetic. IOP was measured in both eyes after completion of all other slit lamp examinations to avoid potential interference with the other evaluations.
Outcome measures
| Measure |
rhNGF 20μg/mL
n=20 Participants
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 Participants
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Change From Baseline in Intraocular Pressure (IOP) by Eye Over All Visits
Study eye - FU 2
|
-0.4 mmHg
Standard Deviation 2.70
|
0.5 mmHg
Standard Deviation 1.51
|
|
Change From Baseline in Intraocular Pressure (IOP) by Eye Over All Visits
Study eye - FU 3
|
-0.4 mmHg
Standard Deviation 3.03
|
-0.3 mmHg
Standard Deviation 2.75
|
|
Change From Baseline in Intraocular Pressure (IOP) by Eye Over All Visits
Non-study eye - FU 2
|
-0.8 mmHg
Standard Deviation 1.92
|
-0.3 mmHg
Standard Deviation 1.49
|
|
Change From Baseline in Intraocular Pressure (IOP) by Eye Over All Visits
Non-study eye - FU 3
|
-0.5 mmHg
Standard Deviation 2.48
|
-0.5 mmHg
Standard Deviation 2.17
|
SECONDARY outcome
Timeframe: On Day 1 (single dose scheme), Days 2,3,6 (multiple dose scheme), Day 7 (Follow-up [FU] 1), Day 8 (FU 2); Day 16 (FU 3)Population: The safety population is represented by randomized subjects who received a dose of study medication in at least one eye. All 30 randomized subjects were included in the Safety population.
Values of Best-Corrected Distance Visual Acuity (BCDVA) scores were measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) score. The ETDRS charts use letters, or a geometric progression in letter size from line to line, under standardized lighting conditions. The patient starts at the top of the chart, or on the last row where he or she can read all of the letters, and reads down the chart until he or she reaches a row where a minimum of three letters on a line cannot be read. The patient is scored by how many letters could be correctly identified. Therefore, the higher the number of letters the higher the visual acuity. Changes in the ETDRS score from baseline are summarised for the study eye.
Outcome measures
| Measure |
rhNGF 20μg/mL
n=20 Participants
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 Participants
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Change From Baseline in Visual Acuity Score for the Study Eye Over All Visits
Day 1 - 8h
|
1.1 Letters
Standard Deviation 3.03
|
0.6 Letters
Standard Deviation 2.76
|
|
Change From Baseline in Visual Acuity Score for the Study Eye Over All Visits
Day 2 - predose
|
0.5 Letters
Standard Deviation 3.47
|
0.4 Letters
Standard Deviation 2.80
|
|
Change From Baseline in Visual Acuity Score for the Study Eye Over All Visits
Day 2 - 8h
|
1.8 Letters
Standard Deviation 4.10
|
2.1 Letters
Standard Deviation 2.77
|
|
Change From Baseline in Visual Acuity Score for the Study Eye Over All Visits
Day 3 - predose
|
0.8 Letters
Standard Deviation 3.27
|
0.1 Letters
Standard Deviation 3.87
|
|
Change From Baseline in Visual Acuity Score for the Study Eye Over All Visits
Day 6 - predose
|
1.6 Letters
Standard Deviation 2.93
|
2.0 Letters
Standard Deviation 3.43
|
|
Change From Baseline in Visual Acuity Score for the Study Eye Over All Visits
Day 6 - 8h
|
1.4 Letters
Standard Deviation 3.72
|
2.5 Letters
Standard Deviation 2.42
|
|
Change From Baseline in Visual Acuity Score for the Study Eye Over All Visits
FU1 - 0h
|
3.1 Letters
Standard Deviation 3.62
|
2.4 Letters
Standard Deviation 1.90
|
|
Change From Baseline in Visual Acuity Score for the Study Eye Over All Visits
FU2 - 8h
|
2.3 Letters
Standard Deviation 3.06
|
1.5 Letters
Standard Deviation 3.17
|
|
Change From Baseline in Visual Acuity Score for the Study Eye Over All Visits
FU3 - 0h
|
2.7 Letters
Standard Deviation 3.59
|
1.4 Letters
Standard Deviation 3.81
|
SECONDARY outcome
Timeframe: On Day 1 (single dose scheme), Days 2,3,6 (multiple dose scheme), Day 7 (Follow-up [FU] 1), Day 8 (FU 2); Day 16 (FU 3)Population: The safety population is represented by randomized subjects who received a dose of study medication in at least one eye. All 30 randomized subjects were included in the Safety population.
LogMAR is the logarithm of the minimal angle of resolution. The LogMAR was derived as - log (Snellen Equivalent result). LogMAR values range from 1.6 (20/800 Snellen Equivalent) to -0.2 (20/12 Snellen Equivalent). The lower the LogMAR value, the better the visual acuity.
Outcome measures
| Measure |
rhNGF 20μg/mL
n=20 Participants
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 Participants
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Change in Baseline in LogMAR [Derived as - Log (Snellen Equivalent Result)] for the Study Eye Over All Visits.
FU3 - 0h
|
-0.054 LogMAR
Standard Deviation 0.0751
|
-0.028 LogMAR
Standard Deviation 0.0901
|
|
Change in Baseline in LogMAR [Derived as - Log (Snellen Equivalent Result)] for the Study Eye Over All Visits.
Day 1 - 8 h
|
-0.025 LogMAR
Standard Deviation 0.0547
|
-0.019 LogMAR
Standard Deviation 0.0757
|
|
Change in Baseline in LogMAR [Derived as - Log (Snellen Equivalent Result)] for the Study Eye Over All Visits.
Day 2 - predose
|
-0.015 LogMAR
Standard Deviation 0.0785
|
0.010 LogMAR
Standard Deviation 0.0536
|
|
Change in Baseline in LogMAR [Derived as - Log (Snellen Equivalent Result)] for the Study Eye Over All Visits.
Day 2 - 8h
|
-0.043 LogMAR
Standard Deviation 0.0731
|
-0.055 LogMAR
Standard Deviation 0.0478
|
|
Change in Baseline in LogMAR [Derived as - Log (Snellen Equivalent Result)] for the Study Eye Over All Visits.
Day 3 - predose
|
-0.025 LogMAR
Standard Deviation 0.0758
|
-0.009 LogMAR
Standard Deviation 0.0539
|
|
Change in Baseline in LogMAR [Derived as - Log (Snellen Equivalent Result)] for the Study Eye Over All Visits.
Day 6 - predose
|
-0.034 LogMAR
Standard Deviation 0.0576
|
-0.037 LogMAR
Standard Deviation 0.0475
|
|
Change in Baseline in LogMAR [Derived as - Log (Snellen Equivalent Result)] for the Study Eye Over All Visits.
day 6 - 8h
|
-0.035 LogMAR
Standard Deviation 0.0743
|
-0.055 LogMAR
Standard Deviation 0.0472
|
|
Change in Baseline in LogMAR [Derived as - Log (Snellen Equivalent Result)] for the Study Eye Over All Visits.
FU 1 - 0h
|
-0.073 LogMAR
Standard Deviation 0.0820
|
-0.055 LogMAR
Standard Deviation 0.0478
|
|
Change in Baseline in LogMAR [Derived as - Log (Snellen Equivalent Result)] for the Study Eye Over All Visits.
FU2 - 8h
|
-0.049 LogMAR
Standard Deviation 0.0684
|
-0.018 LogMAR
Standard Deviation 0.0594
|
SECONDARY outcome
Timeframe: On Day 1 (single dose scheme), Days 2,3,6 (multiple dose scheme), Day 7 (Follow-up [FU] 1), Day 8 (FU 2); Day 16 (FU 3)Population: The safety population is represented by randomized subjects who received a dose of study medication in at least one eye. All 30 randomized subjects were included in the Safety population.
The TFBUT was performed after instillation of 5 μl of 2% preservative-free sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye. With the aid of a slit lamp at 10X magnification using cobalt blue illumination, the examiner will monitor the integrity of the tear film, noting the time it takes to form lacunae (clear spaces in the tear film) from the time that the eye is opened after the last blink. The range of TFBUT normality in this trial is \> 8' to 12' in either eye at screening or baseline. The longer the time the better the integrity of the tear film.
Outcome measures
| Measure |
rhNGF 20μg/mL
n=20 Participants
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 Participants
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Change From Baseline in Tear Film Break-Up Time (TFBUT) for the Study Eye Over All Visits..
Day 1 - 8h1
|
-1.343 seconds
Standard Deviation 2.0648
|
-1.187 seconds
Standard Deviation 1.5874
|
|
Change From Baseline in Tear Film Break-Up Time (TFBUT) for the Study Eye Over All Visits..
Day 2 - predose
|
-1.370 seconds
Standard Deviation 1.9129
|
-1.227 seconds
Standard Deviation 1.3582
|
|
Change From Baseline in Tear Film Break-Up Time (TFBUT) for the Study Eye Over All Visits..
Day 2 - 8h
|
-1.000 seconds
Standard Deviation 1.9806
|
-1.761 seconds
Standard Deviation 1.3983
|
|
Change From Baseline in Tear Film Break-Up Time (TFBUT) for the Study Eye Over All Visits..
Day 3 - predose
|
-0.612 seconds
Standard Deviation 2.4824
|
0.344 seconds
Standard Deviation 2.3712
|
|
Change From Baseline in Tear Film Break-Up Time (TFBUT) for the Study Eye Over All Visits..
Day 6 - predose
|
-0.593 seconds
Standard Deviation 2.5198
|
-1.442 seconds
Standard Deviation 1.6595
|
|
Change From Baseline in Tear Film Break-Up Time (TFBUT) for the Study Eye Over All Visits..
Day 6 - 8h
|
-0.892 seconds
Standard Deviation 2.0086
|
-1.892 seconds
Standard Deviation 1.5450
|
|
Change From Baseline in Tear Film Break-Up Time (TFBUT) for the Study Eye Over All Visits..
FU1 - 0h
|
-0.768 seconds
Standard Deviation 2.0851
|
0.462 seconds
Standard Deviation 1.3560
|
|
Change From Baseline in Tear Film Break-Up Time (TFBUT) for the Study Eye Over All Visits..
FU2 - 8h
|
-0.610 seconds
Standard Deviation 1.8211
|
-0.655 seconds
Standard Deviation 2.4522
|
|
Change From Baseline in Tear Film Break-Up Time (TFBUT) for the Study Eye Over All Visits..
FU3 - 0h
|
-0.795 seconds
Standard Deviation 2.1053
|
-0.800 seconds
Standard Deviation 1.4070
|
SECONDARY outcome
Timeframe: On Day 1 (single dose scheme), Days 2,3,6 (multiple dose scheme), Day 7 (Follow-up [FU] 1), Day 8 (FU 2); Day 16 (FU 3)Population: The safety population is represented by randomized subjects who received a dose of study medication in at least one eye. All 30 randomized subjects were included in the Safety population.
Corneal Staining was derived as the sum of scores of the five corneal sectors (central, superior, inferior, nasal, and temporal) each of which was scored on a scale of 0-3, with a minimum score of 0 and a maximal score of 15 (sum \> 3 out of 15 is abnormal).
Outcome measures
| Measure |
rhNGF 20μg/mL
n=20 Participants
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 Participants
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Change From Baseline in Overall National Eye Institute (NEI) Score for the Study Eye Over All Visits.
Day 1 - 8h1
|
0.00 score on a scale
Standard Deviation 0.00
|
0.00 score on a scale
Standard Deviation 0.00
|
|
Change From Baseline in Overall National Eye Institute (NEI) Score for the Study Eye Over All Visits.
Day 2 - predose
|
0.5 score on a scale
Standard Deviation 1.23
|
0.5 score on a scale
Standard Deviation 1.27
|
|
Change From Baseline in Overall National Eye Institute (NEI) Score for the Study Eye Over All Visits.
Day 2 - 8h
|
0.1 score on a scale
Standard Deviation 0.22
|
0.0 score on a scale
Standard Deviation 0.00
|
|
Change From Baseline in Overall National Eye Institute (NEI) Score for the Study Eye Over All Visits.
Day 3 - predose
|
0.7 score on a scale
Standard Deviation 1.79
|
0.6 score on a scale
Standard Deviation 1.90
|
|
Change From Baseline in Overall National Eye Institute (NEI) Score for the Study Eye Over All Visits.
Day 6 - predose
|
0.4 score on a scale
Standard Deviation 1.35
|
0.0 score on a scale
Standard Deviation 0.00
|
|
Change From Baseline in Overall National Eye Institute (NEI) Score for the Study Eye Over All Visits.
Day 6 - 8h
|
0.0 score on a scale
Standard Deviation 0.00
|
0.0 score on a scale
Standard Deviation 0.00
|
|
Change From Baseline in Overall National Eye Institute (NEI) Score for the Study Eye Over All Visits.
FU1 - 0h
|
0.7 score on a scale
Standard Deviation 1.42
|
0.0 score on a scale
Standard Deviation 0.00
|
|
Change From Baseline in Overall National Eye Institute (NEI) Score for the Study Eye Over All Visits.
FU2 - 8h
|
0.1 score on a scale
Standard Deviation 0.45
|
0.0 score on a scale
Standard Deviation 0.00
|
|
Change From Baseline in Overall National Eye Institute (NEI) Score for the Study Eye Over All Visits.
FU3 - 0h
|
0.1 score on a scale
Standard Deviation 0.45
|
0.0 score on a scale
Standard Deviation 0.00
|
SECONDARY outcome
Timeframe: On Day 1 (single dose scheme), Days 2,3,6 (multiple dose scheme), Day 7 (Follow-up [FU] 1), Day 8 (FU 2); Day 16 (FU 3)Population: The safety population is represented by randomized subjects who received a dose of study medication in at least one eye. All 30 randomized subjects were included in the Safety population.
The course of VAS ocular tolerability score by eye over all visits was assessed. Only data "Overall" for study's eye are reported hereunder. A ocular tolerability score was determined using a 100 mm VAS on which 0 meant No symptoms and 100 meant the Worst possible discomfort. The patients subjectively evaluated their ocular symptoms (foreign body sensation, burning or stinging, itching, pain, sticky feeling, blurred vision and photophobia) using the VAS giving the value they were feeling from none to an extreme value. The ocular symptoms were evaluated by the patients through the scale.
Outcome measures
| Measure |
rhNGF 20μg/mL
n=20 Participants
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 Participants
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Course of Visual Analogue Scale (VAS) Ocular Tolerability Score for the Study Eye Over All Visits.
Day 1 - 8h
|
0.46 score on a scale
Standard Deviation 0.890
|
0.09 score on a scale
Standard Deviation 0.154
|
|
Course of Visual Analogue Scale (VAS) Ocular Tolerability Score for the Study Eye Over All Visits.
Day 2 - predose
|
0.66 score on a scale
Standard Deviation 1.739
|
0.31 score on a scale
Standard Deviation 0.461
|
|
Course of Visual Analogue Scale (VAS) Ocular Tolerability Score for the Study Eye Over All Visits.
Day 2 - 8h
|
0.81 score on a scale
Standard Deviation 1.703
|
0.23 score on a scale
Standard Deviation 0.358
|
|
Course of Visual Analogue Scale (VAS) Ocular Tolerability Score for the Study Eye Over All Visits.
Day 3 - predose
|
1.14 score on a scale
Standard Deviation 2.066
|
0.46 score on a scale
Standard Deviation 0.499
|
|
Course of Visual Analogue Scale (VAS) Ocular Tolerability Score for the Study Eye Over All Visits.
Day 6 - predose
|
2.26 score on a scale
Standard Deviation 5.132
|
0.49 score on a scale
Standard Deviation 0.661
|
|
Course of Visual Analogue Scale (VAS) Ocular Tolerability Score for the Study Eye Over All Visits.
Day 6 - 8h
|
2.51 score on a scale
Standard Deviation 7.089
|
0.26 score on a scale
Standard Deviation 0.268
|
|
Course of Visual Analogue Scale (VAS) Ocular Tolerability Score for the Study Eye Over All Visits.
FU1 - 0h
|
1.32 score on a scale
Standard Deviation 3.548
|
0.19 score on a scale
Standard Deviation 0.337
|
|
Course of Visual Analogue Scale (VAS) Ocular Tolerability Score for the Study Eye Over All Visits.
FU2 - 8h
|
1.06 score on a scale
Standard Deviation 3.727
|
0.01 score on a scale
Standard Deviation 0.045
|
|
Course of Visual Analogue Scale (VAS) Ocular Tolerability Score for the Study Eye Over All Visits.
Fu3 - 0h
|
0.44 score on a scale
Standard Deviation 0.578
|
0.30 score on a scale
Standard Deviation 0.428
|
SECONDARY outcome
Timeframe: On Day 1 (single dose scheme), Days 2,3,6 (multiple dose scheme), Day 7 (Follow-up [FU] 1), Day 8 (FU 2); Day 16 (FU 3)Population: The safety population is represented by randomized subjects who received a dose of study medication in at least one eye. All 30 randomized subjects were included in the Safety population.
Intraindividual differences between study eye and non-study (fellow) eye at all study visits were assessed. Data "overall" are reported hereunder.A ocular tolerability score was determined using a 100 mm VAS on which 0 meant No symptoms and 100 meant the Worst possible discomfort. The patients subjectively evaluated their ocular symptoms (foreign body sensation, burning or stinging, itching, pain, sticky feeling, blurred vision and photophobia) using the VAS giving the value they were feeling from none to an extreme value. The ocular symptoms were evaluated by the patients through the scale.
Outcome measures
| Measure |
rhNGF 20μg/mL
n=20 Participants
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 Participants
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Intraindividual Change in VAS Ocular Tolerability Scores Between Study Eye and Fellow (Non-study) Eye at All Study Visits
Day 1 - 8h
|
0.04 score on a scale
Standard Deviation 0.258
|
-0.06 score on a scale
Standard Deviation 0.168
|
|
Intraindividual Change in VAS Ocular Tolerability Scores Between Study Eye and Fellow (Non-study) Eye at All Study Visits
Day 2 - predose
|
0.29 score on a scale
Standard Deviation 1.024
|
0.10 score on a scale
Standard Deviation 0.286
|
|
Intraindividual Change in VAS Ocular Tolerability Scores Between Study Eye and Fellow (Non-study) Eye at All Study Visits
Day 2 - 8h
|
0.11 score on a scale
Standard Deviation 0.560
|
-0.07 score on a scale
Standard Deviation 0.205
|
|
Intraindividual Change in VAS Ocular Tolerability Scores Between Study Eye and Fellow (Non-study) Eye at All Study Visits
Day 3 - predose
|
0.54 score on a scale
Standard Deviation 1.412
|
0.13 score on a scale
Standard Deviation 0.519
|
|
Intraindividual Change in VAS Ocular Tolerability Scores Between Study Eye and Fellow (Non-study) Eye at All Study Visits
Day 6 - predose
|
1.16 score on a scale
Standard Deviation 3.537
|
0.27 score on a scale
Standard Deviation 0.698
|
|
Intraindividual Change in VAS Ocular Tolerability Scores Between Study Eye and Fellow (Non-study) Eye at All Study Visits
Day 6 - 8h
|
2.03 score on a scale
Standard Deviation 6.942
|
-0.09 score on a scale
Standard Deviation 0.303
|
|
Intraindividual Change in VAS Ocular Tolerability Scores Between Study Eye and Fellow (Non-study) Eye at All Study Visits
FU1 - 0h
|
0.72 score on a scale
Standard Deviation 2.823
|
0.04 score on a scale
Standard Deviation 0.096
|
|
Intraindividual Change in VAS Ocular Tolerability Scores Between Study Eye and Fellow (Non-study) Eye at All Study Visits
FU2 - 8h
|
0.87 score on a scale
Standard Deviation 3.697
|
-0.03 score on a scale
Standard Deviation 0.090
|
|
Intraindividual Change in VAS Ocular Tolerability Scores Between Study Eye and Fellow (Non-study) Eye at All Study Visits
FU3 - 0h
|
0.04 score on a scale
Standard Deviation 0.346
|
0.00 score on a scale
Standard Deviation 0.243
|
SECONDARY outcome
Timeframe: Day 1 (Pre-Dose, 0.5, 2, 4, 8, 9, 10, 11, 12, 14, 16 hr) and Day 2 (Pre-Dose, 0.5, 2, 4, 6, 8, 10, 10.5, 11, 12, 13, 14, 16 hr),Population: PK-Set (PKS), defined as all subjects completing the PK sampling according to the study protocol and who did not show serious protocol deviations or non-compliance.
Time points for rhNGF plasma levels measurement were the following: Day 1 (Pre-Dose, 0.5, 2, 4, 8, 9, 10, 11, 12, 14, 16 hr), Day 2 (Pre-Dose, 0.5, 2, 4, 6, 8, 10, 10.5, 11, 12, 13, 14, 16 hr), Day 3 (Pre-Dose, 2, 4, 6, 8, 10 hr), Day 4 Pre-Dose, Day 5 Pre-Dose, Day 6 (Pre-Dose, 4, 8, 10, 10.5, 11, 12, 13, 14, 16 hr), FU 1 0 hr, FU 2 (0 and 8 hr), and FU 3 0 hr. Values are reported for the single-dose regimen (Day 1) and the first day of the multiple-dose regimen (Day 2). From Day 1, most values were below the detectable level (i.e. \<32 pg/ml). Values below this value are reported as not applicable (NA).
Outcome measures
| Measure |
rhNGF 20μg/mL
n=20 Participants
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 Participants
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 2 - 2 hr
|
NA pg/ml
Standard Error 93.63
values were below the detectable level (i.e. \<32 pg/ml)
|
1.02 pg/ml
Standard Error 0
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 1 - 11 hr
|
NA pg/ml
Standard Error 82.12
values were below the detectable level (i.e. \<32 pg/ml)
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 1 - 12 hr
|
33.10 pg/ml
Standard Error 110.96
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 1 - 14 hr
|
NA pg/ml
Standard Error 79.92
values were below the detectable level (i.e. \<32 pg/ml)
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 1 - 16 hr
|
35.88 pg/ml
Standard Error 117.91
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 2 - Pre-Dose
|
33.87 pg/ml
Standard Error 113.95
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 2 - 0.5 hr
|
32.30 pg/ml
Standard Error 108.85
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 2 - 4 hr
|
NA pg/ml
Standard Error 77.01
values were below the detectable level (i.e. \<32 pg/ml)
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 2 - 6 hr
|
NA pg/ml
Standard Error 83.02
values were below the detectable level (i.e. \<32 pg/ml)
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 2 - 8 hr
|
NA pg/ml
Standard Error 90.77
values were below the detectable level (i.e. \<32 pg/ml)
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 2 - 10 hr
|
NA pg/ml
Standard Error 90.40
values were below the detectable level (i.e. \<32 pg/ml)
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 2 - 10.5 hr
|
34.68 pg/ml
Standard Error 113.00
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 2 - 11 hr
|
37.42 pg/ml
Standard Error 120.37
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 2 - 12 hr
|
32.22 pg/ml
Standard Error 100.26
|
NA pg/ml
Standard Error 36.51
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 2 - 13 hr
|
NA pg/ml
Standard Error 81.69
values were below the detectable level (i.e. \<32 pg/ml)
|
NA pg/ml
Standard Error 34.96
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 2 - 14 hr
|
NA pg/ml
Standard Error 96.51
values were below the detectable level (i.e. \<32 pg/ml)
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 2 - 16 hr
|
NA pg/ml
Standard Error 101.13
values were below the detectable level (i.e. \<32 pg/ml)
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 1 - Pre-Dose
|
NA pg/ml
Standard Error 94.16
values were below the detectable level (i.e. \<32 pg/ml)
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 1 - 0.5 hr
|
NA pg/ml
Standard Error 83.06
values were below the detectable level (i.e. \<32 pg/ml)
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 1 - 2 hr
|
NA pg/ml
Standard Error 66.73
values were below the detectable level (i.e. \<32 pg/ml)
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 1 - 4 hr
|
35.69 pg/ml
Standard Error 113.04
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 1 - 8 hr
|
NA pg/ml
Standard Error 63.34
values were below the detectable level (i.e. \<32 pg/ml)
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 1 - 9 hr
|
NA pg/ml
Standard Error 95.53
values were below the detectable level (i.e. \<32 pg/ml)
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay I (ELISA I)
Day 1 - 10 hr
|
34.12 pg/ml
Standard Error 94.85
|
NA pg/ml
Standard Error NA
values were below the detectable level (i.e. \<32 pg/ml)
|
SECONDARY outcome
Timeframe: Day 1 (Pre-Dose, 0.5, 2, 4, 8, 9, 10, 11, 12, 14, 16 hr) and Day 2 (Pre-Dose, 0.5, 2, 4, 8, 9, 10, 10.5, 11, 12, 13, 14, 16 hr)Population: PK-Set (PKS), defined as all subjects completing the PK sampling according to the study protocol and who did not show serious protocol deviations or non-compliance.
Time points for rhNGF plasma levels measurement were the following: Day 1 (Pre-Dose, 0.5, 2, 4, 8, 9, 10, 11, 12, 14, 16 hr), Day 2 (Pre-Dose, 0.5, 2, 4, 6, 8, 10, 10.5, 11, 12, 13, 14, 16 hr), Day 3 (Pre-Dose, 2, 4, 6, 8, 10 hr), Day 4 Pre-Dose, Day 5 Pre-Dose, Day 6 (Pre-Dose, 4, 8, 10, 10.5, 11, 12, 13, 14, 16 hr), FU 1 0 hr, FU 2 (0 and 8 hr), and FU 3 0 hr. Values are reported for the single-dose regimen (Day 1) and the first day of the multiple-dose regimen (Day 2). From Day 1, most values were below the detectable level (i.e. \<15 pg/ml). Values below this value are reported as not applicable (NA).
Outcome measures
| Measure |
rhNGF 20μg/mL
n=20 Participants
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 Participants
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 1 - Pre-Dose
|
39.22 pg/ml
Standard Deviation 105.51
|
NA pg/ml
Standard Deviation 36.08
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 1 - 0.5 hr
|
36.28 pg/ml
Standard Deviation 99.46
|
NA pg/ml
Standard Deviation 31.31
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 1 - 2 hr
|
38.52 pg/ml
Standard Deviation 105.06
|
NA pg/ml
Standard Deviation 28.70
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 1 - 4 hr
|
39.43 pg/ml
Standard Deviation 111.73
|
NA pg/ml
Standard Deviation 30.72
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 1 - 8 hr
|
33.76 pg/ml
Standard Deviation 90.93
|
NA pg/ml
Standard Deviation 31.69
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 1 - 9 hr
|
35.27 pg/ml
Standard Deviation 94.70
|
NA pg/ml
Standard Deviation 29.23
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 1 - 10 hr
|
28.77 pg/ml
Standard Deviation 68.13
|
NA pg/ml
Standard Deviation 23.69
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 1 - 11 hr
|
34.87 pg/ml
Standard Deviation 95.60
|
NA pg/ml
Standard Deviation 33.46
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 1 - 12 hr
|
31.97 pg/ml
Standard Deviation 86.13
|
NA pg/ml
Standard Deviation 32.38
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 1 - 14 hr
|
34.23 pg/ml
Standard Deviation 89.93
|
NA pg/ml
Standard Deviation 30.36
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 1 - 16 hr
|
39.29 pg/ml
Standard Deviation 111.35
|
NA pg/ml
Standard Deviation 25.93
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 2 - Pre-Dose
|
39.53 pg/ml
Standard Deviation 113.26
|
NA pg/ml
Standard Deviation 32.57
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 2 - 0.5 hr
|
34.35 pg/ml
Standard Deviation 98.20
|
NA pg/ml
Standard Deviation 36.71
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 2 - 2 hr
|
38.27 pg/ml
Standard Deviation 103.68
|
NA pg/ml
Standard Deviation 37.84
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 2 - 4 hr
|
35.51 pg/ml
Standard Deviation 96.54
|
17.02 pg/ml
Standard Deviation 41.93
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 2 - 6 hr
|
38.43 pg/ml
Standard Deviation 106.00
|
NA pg/ml
Standard Deviation 31.75
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 2 - 8 hr
|
33.90 pg/ml
Standard Deviation 93.43
|
NA pg/ml
Standard Deviation 26.91
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 2 - 10 hr
|
37.84 pg/ml
Standard Deviation 102.03
|
NA pg/ml
Standard Deviation 27.13
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 2 - 10.5 hr
|
39.64 pg/ml
Standard Deviation 110.40
|
NA pg/ml
Standard Deviation 26.77
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 2 - 11 hr
|
44.55 pg/ml
Standard Deviation 121.82
|
NA pg/ml
Standard Deviation 26.51
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 2 - 12 hr
|
37.81 pg/ml
Standard Deviation 101.13
|
NA pg/ml
Standard Deviation 34.16
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 2 - 13 hr
|
39.35 pg/ml
Standard Deviation 104.93
|
NA pg/ml
Standard Deviation 33.78
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 2 - 14 hr
|
37.31 pg/ml
Standard Deviation 99.77
|
NA pg/ml
Standard Deviation 27.79
values were below the detectable level (i.e. \<32 pg/ml)
|
|
Kinetics of rhNGF Plasma Levels After Single-dose Administration and Multiple-dose Administration Through Enzyme-Linked Immunosorbent Assay II (ELISA II)
Day 2 - 16 hr
|
40.55 pg/ml
Standard Deviation 118.50
|
NA pg/ml
Standard Deviation 16.32
values were below the detectable level (i.e. \<32 pg/ml)
|
Adverse Events
rhNGF 20μg/mL
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
rhNGF 20μg/mL
n=20 participants at risk
rhNGF 20μg/mL eye drop solution, formulation containing L-methionine as excipient.
rhNGF 20μg/mL: Study Eye (For subjects randomized to rhNGF group) Day 1: One drop instilled into study eye (35 μL, corresponding to 0.70 μg of rhNGF).
Day 2, 3, 4, 5, 6: One drop six times a day (every 2h) into study eye (210 μL, corresponding to 4.20 μg of rhNGF).
Total dose in the study eye will be 31 drops (1085 μL, equivalent to 21.7 μg rhNGF) over 6 days.
|
Placebo
n=10 participants at risk
Vehicle: formulation containing L-methionine as excipient.
Placebo: Vehicle: formulation containing L-methionine as excipient.
|
|---|---|---|
|
Investigations
Alanine aminotransferase increased
|
10.0%
2/20 • Number of events 2 • From Day -1 to Day 42
|
10.0%
1/10 • Number of events 1 • From Day -1 to Day 42
|
|
Investigations
Aspartate aminotransferase incresed
|
10.0%
2/20 • Number of events 2 • From Day -1 to Day 42
|
10.0%
1/10 • Number of events 1 • From Day -1 to Day 42
|
|
Investigations
Vital dye staining corneal present
|
25.0%
5/20 • Number of events 9 • From Day -1 to Day 42
|
30.0%
3/10 • Number of events 4 • From Day -1 to Day 42
|
|
Infections and infestations
Conjunctivitis
|
30.0%
6/20 • Number of events 6 • From Day -1 to Day 42
|
0.00%
0/10 • From Day -1 to Day 42
|
|
Eye disorders
Eye pain
|
10.0%
2/20 • Number of events 2 • From Day -1 to Day 42
|
0.00%
0/10 • From Day -1 to Day 42
|
|
Eye disorders
Eye pruritus
|
0.00%
0/20 • From Day -1 to Day 42
|
10.0%
1/10 • Number of events 1 • From Day -1 to Day 42
|
|
Eye disorders
Eye irritation
|
5.0%
1/20 • Number of events 1 • From Day -1 to Day 42
|
0.00%
0/10 • From Day -1 to Day 42
|
|
Gastrointestinal disorders
Aphthous ulcer
|
5.0%
1/20 • Number of events 1 • From Day -1 to Day 42
|
10.0%
1/10 • Number of events 1 • From Day -1 to Day 42
|
|
General disorders
Catheter site oedema
|
5.0%
1/20 • Number of events 1 • From Day -1 to Day 42
|
0.00%
0/10 • From Day -1 to Day 42
|
|
General disorders
Injection site reaction
|
0.00%
0/20 • From Day -1 to Day 42
|
10.0%
1/10 • Number of events 1 • From Day -1 to Day 42
|
|
Nervous system disorders
Headache
|
5.0%
1/20 • Number of events 1 • From Day -1 to Day 42
|
0.00%
0/10 • From Day -1 to Day 42
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.0%
1/20 • Number of events 2 • From Day -1 to Day 42
|
0.00%
0/10 • From Day -1 to Day 42
|
Additional Information
Clinical Development & Operations
Dompé farmaceutici s.p.a.
Phone: +39 02 513831
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place