Trial Outcomes & Findings for Study to Evaluate Safety and Efficacy of rhNGF Eye Drops Solution Versus Vehicle in Patients With Glaucoma (NCT NCT02855450)

Last Updated: 2020-11-25

Results Overview

Unexpected Severe Progression Of Optic Neuropathy (USPON) is a composed parameter which required at least 28 single evaluations; it occurred if the subject answered Yes to any of the following 4 questions on unexpected severe progression: * Best Corrected Distance Visual Acuity (BCDVA): 'Yes' for at least one treated eye at any Follow-Up Visit after first study drug dose * Humphrey Visual Field (HVF): 'Yes' for at least one treated eye in at least one assessment during treatment or follow-up period * Electroretinography (ERG): 'Yes' for at least one treated eye at any Follow-Up Visit after first study drug dose * Optical Coherence tomography (OCT): 'Yes' for at least one treated eye at any Follow-Up Visit after first study drug dose Intolerance and allergy to the drug was identified based on preferred term of treatment-emergent adverse events. URAEs are unexpected related AE affecting ocular function. Local/systemic toxicities were identified via the AE form

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

60 participants

Primary outcome timeframe

At day 56/end of treatment

Results posted on

2020-11-25

Participant Flow

Participant milestones

Participant milestones
Measure	rhNGF rhNGF (Recombinant Human Nerve Growth Factor) 180 μg/ml eye drops solution rhNGF: Recombinant Human Nerve Growth Factor 180μg/ml (one 35 μl drop equals to 6.30 μg of rhNGF) reconstituted solution three times a day (TID) for 8 weeks of treatment.	Vehicle Ophthalmic Placebo solution Vehicle: Ophthalmic Placebo solution of the same composition as the test product with the exception of rhNGF reconstituted solution times a day (TID) for 8 weeks of treatment.
Overall Study STARTED	40	20
Overall Study COMPLETED	35	20
Overall Study NOT COMPLETED	5	0

Reasons for withdrawal

Reasons for withdrawal
Measure	rhNGF rhNGF (Recombinant Human Nerve Growth Factor) 180 μg/ml eye drops solution rhNGF: Recombinant Human Nerve Growth Factor 180μg/ml (one 35 μl drop equals to 6.30 μg of rhNGF) reconstituted solution three times a day (TID) for 8 weeks of treatment.	Vehicle Ophthalmic Placebo solution Vehicle: Ophthalmic Placebo solution of the same composition as the test product with the exception of rhNGF reconstituted solution times a day (TID) for 8 weeks of treatment.
Overall Study Adverse Event	1	0
Overall Study Lost to Follow-up	4	0

Baseline Characteristics

Study to Evaluate Safety and Efficacy of rhNGF Eye Drops Solution Versus Vehicle in Patients With Glaucoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	rhNGF n=40 Participants rhNGF (Recombinant Human Nerve Growth Factor) 180 μg/ml eye drops solution rhNGF: Recombinant Human Nerve Growth Factor 180μg/ml (one 35 μl drop equals to 6.30 μg of rhNGF) reconstituted solution three times a day (TID) for 8 weeks of treatment.	Vehicle n=20 Participants Ophthalmic Placebo solution Vehicle: Ophthalmic Placebo solution of the same composition as the test product with the exception of rhNGF reconstituted solution times a day (TID) for 8 weeks of treatment.	Total n=60 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	15 Participants n=5 Participants	12 Participants n=7 Participants	27 Participants n=5 Participants
Age, Categorical >=65 years	25 Participants n=5 Participants	8 Participants n=7 Participants	33 Participants n=5 Participants
Age, Continuous	68.0 years STANDARD_DEVIATION 13.98 • n=5 Participants	62.2 years STANDARD_DEVIATION 13.28 • n=7 Participants	66.1 years STANDARD_DEVIATION 13.92 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	9 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	11 Participants n=7 Participants	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	38 Participants n=5 Participants	19 Participants n=7 Participants	57 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	40 participants n=5 Participants	20 participants n=7 Participants	60 participants n=5 Participants

PRIMARY outcome

Timeframe: At day 56/end of treatment

Population: Safety Set (SAF). The Safety Set includes all randomized subjects who received at least one dose of study medication. This safety population is used in the analysis of all safety endpoints. All analyses based on the SAF are summarized by the treatment received

Outcome measures

Outcome measures
Measure	rhNGF n=40 Participants rhNGF (Recombinant Human Nerve Growth Factor) 180 μg/ml eye drops solution rhNGF: Recombinant Human Nerve Growth Factor 180μg/ml (one 35 μl drop equals to 6.30 μg of rhNGF) reconstituted solution three times a day (TID) for 8 weeks of treatment.	Vehicle n=20 Participants Ophthalmic Placebo solution Vehicle: Ophthalmic Placebo solution of the same composition as the test product with the exception of rhNGF reconstituted solution times a day (TID) for 8 weeks of treatment.
Incidence of Events as of Primary Safety Outcomes USPON	0 Number of events	2 Number of events
Incidence of Events as of Primary Safety Outcomes USPON during treatment period	0 Number of events	0 Number of events
Incidence of Events as of Primary Safety Outcomes Intolerance to the drug	6 Number of events	0 Number of events
Incidence of Events as of Primary Safety Outcomes Ocular URAEs	1 Number of events	1 Number of events
Incidence of Events as of Primary Safety Outcomes Local/systemic toxicities	0 Number of events	0 Number of events

PRIMARY outcome

Timeframe: Change from baseline to days 7, 28 and 56 (Treatment period), and Day 84 (Follow up)

Population: The Safety Set includes all randomized subjects who received at least one dose of study medication. This safety population is used in the analysis of all safety endpoints. All analyses based on the SAF are summarized by the treatment received. Please note that there were major protocol deviations, so that no complete VAS data was reported during treatment period; for this reason the numbers of participants analyzed per row may differ from the Overall Numbers of Participants.

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. Only "overall" values for primary eye and secondary eye are reported here under. An eye was considered as Primary eye, if * the eye was treated and * the investigator considered this eye as qualifying eye. * If both eyes were considered as qualifying eye, the right eye was chosen. The other eye was then considered as Secondary eye, if the eye was treated.

Outcome measures

Outcome measures
Measure	rhNGF n=40 Participants rhNGF (Recombinant Human Nerve Growth Factor) 180 μg/ml eye drops solution rhNGF: Recombinant Human Nerve Growth Factor 180μg/ml (one 35 μl drop equals to 6.30 μg of rhNGF) reconstituted solution three times a day (TID) for 8 weeks of treatment.	Vehicle n=20 Participants Ophthalmic Placebo solution Vehicle: Ophthalmic Placebo solution of the same composition as the test product with the exception of rhNGF reconstituted solution times a day (TID) for 8 weeks of treatment.
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score Day 7 - primary eye	2.8 score on a scale Standard Deviation 9.09	-2.1 score on a scale Standard Deviation 5.95
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score Day 28 - primary eye	4.0 score on a scale Standard Deviation 11.22	1.0 score on a scale Standard Deviation 11.85
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score Day 56 - primary eye	3.6 score on a scale Standard Deviation 16.08	-0.9 score on a scale Standard Deviation 6.51
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score Day 84 - primary eye	-0.3 score on a scale Standard Deviation 11.81	0.3 score on a scale Standard Deviation 6.78
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score Day 7 - secondary eye	2.1 score on a scale Standard Deviation 9.44	-1.4 score on a scale Standard Deviation 6.45
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score Day 28 - secondary eye	4.6 score on a scale Standard Deviation 13.25	1.2 score on a scale Standard Deviation 12.16
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score Day 56 - secondary eye	4.5 score on a scale Standard Deviation 16.64	0.6 score on a scale Standard Deviation 10.60
Change From Baseline in Visual Analogue Scale (VAS) Ocular Tolerability Score Day 84 - secondary eye	-0.7 score on a scale Standard Deviation 12.95	1.5 score on a scale Standard Deviation 10.71

Adverse Events

rhNGF

Serious events: 3 serious events

Other events: 31 other events

Deaths: 0 deaths

Vehicle

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	rhNGF n=40 participants at risk rhNGF (Recombinant Human Nerve Growth Factor) 180 μg/ml eye drops solution rhNGF: Recombinant Human Nerve Growth Factor 180μg/ml (one 35 μl drop equals to 6.30 μg of rhNGF) reconstituted solution three times a day (TID) for 8 weeks of treatment.	Vehicle n=20 participants at risk Ophthalmic Placebo solution Vehicle: Ophthalmic Placebo solution of the same composition as the test product with the exception of rhNGF reconstituted solution times a day (TID) for 8 weeks of treatment.
Cardiac disorders Angina unstable	0.00% 0/40 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.	5.0% 1/20 • Number of events 1 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.
Cardiac disorders Atrial fibrillation	2.5% 1/40 • Number of events 1 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.	0.00% 0/20 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.
Cardiac disorders Cardiac failure congestive	2.5% 1/40 • Number of events 1 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.	0.00% 0/20 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.
Metabolism and nutrition disorders Hyperglycaemia	2.5% 1/40 • Number of events 1 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.	0.00% 0/20 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.
Metabolism and nutrition disorders Hyponatraemia	2.5% 1/40 • Number of events 1 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.	0.00% 0/20 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.
Infections and infestations Mycobacterium avium complex infection	0.00% 0/40 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.	5.0% 1/20 • Number of events 1 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/40 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.	5.0% 1/20 • Number of events 1 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mycosis fungoides	2.5% 1/40 • Number of events 1 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.	0.00% 0/20 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.
Nervous system disorders Cerebral infarction	2.5% 1/40 • Number of events 1 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.	0.00% 0/20 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.
Vascular disorders Aortic stenosis	2.5% 1/40 • Number of events 1 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.	0.00% 0/20 • Treatment period: Day 0 (Therapy initiation), Day 7, Day 28, Day 56; Follow-up: Day 84, Day 224 A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that started on or after the date of the First Study Treatment Administration. An AE was considered as TEAE if the Electronic Case Report Form question 'Did the event occurred:' was answered either with 'During Treatment Period' or 'During Follow-Up Period'.

Other adverse events

Additional Information

Flavio Mantelli, MD, PhD

Dompè

Phone: +39 02583831

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place