A Phase 1/2 interventional study of rhNGF 10 μg/ml and rhNGF 20 μg/ml in Neurotrophic Keratitis, Keratitis and Corneal Ulcer, sponsored by Dompé Farmaceutici S.p.A. Completed at 34 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-04-19.
Sponsored by Dompé Farmaceutici S.p.A · Phase 1/2, Interventional, and Treatment
This study is aimed at assessing the safety and the efficacy of two dose regimens of recombinant human nerve growth factor (rhNGF) eye drops solution compared to vehicle for inducing a complete healing of stage 2 (persistent epithelial defect) and 3 (corneal ulcer) neurotrophic keratitis
The primary objective of this study is to assess the safety and the efficacy of two dose regimens (10 µg/ml or 20 µg/ml 6 times a day) of recombinant human nerve growth factor (rhNGF) eye drops solution compared to vehicle for inducing a complete healing of stage 2 (persistent epithelial defect) and 3 (corneal ulcer) neurotrophic keratitis (NK) as measured by the Reading Center evaluating the clinical pictures of corneal fluorescein staining.
Secondary objectives of the study are to assess the duration of complete healing, improvement in visual acuity and improvement in corneal sensitivity following treatment with rhNGF eye drops solution
This is a combined phase I/II study. The phase I and II segments of the study will be conducted as an 8 week, randomized, double-masked, vehicle controlled, parallel group study (referred to as the controlled treatment period) followed by a 48 or 56 week follow-up period The design of the phase I and phase II segments of the study are identical with the exception that in the phase I segment of the study the randomization scheme is different and patients will be followed with additional safety assessments and blood samples for PK (pharmacokinetic) profiling In the ascending dose Phase I segment of the study two doses of rhNGF 10 and 20 µg/ml will be evaluated in a sequential manner
63 studies on the registry are indexed under Corneal Ulcer; 8 are open to participants now.
This study's enrollment of 174 is above the median of 60 across 45 interventional studies indexed under Corneal Ulcer.
Browse Corneal Ulcer studies →Dompé Farmaceutici S.p.A is the lead sponsor of 52 studies on the registry; 4 are open to participants now.
Of its 18 completed or terminated interventional studies of FDA-regulated products, 18 (100%) have results posted.
Compared within Corneal Ulcer, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Keratitis. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
active treatment with rhNGF 10 μg/ml. One drop six times a day (one 35 μl drop equals to 0.35μg of rhNGF).
Drug: rhNGF 10 μg/ml
active treatment with rhNGF 20 μg/ml. One drop 6 times a day (one 35 μl drop equals to 0.70 μg of rhNGF)
Drug: rhNGF 20 μg/ml
vehicle control arm. Ophthalmic solution of the same composition as the test product with the exception of rhNGF. One drop six times a day for the entire period
Other: vehicle
active treatment with rhNGF 10 μg/ml. One drop six times a day (one 35 μl drop equals to 0.35 μg of rhNGF)
Drug: rhNGF 10 μg/ml
active treatment with rhNGF 20 μg/ml. One drop 6 times a day (one 35 μl drop equals to 0.70 μg of rhNGF)
Drug: rhNGF 20 μg/ml
vehicle control arm. Ophthalmic solution of the same composition as the test product with the exception of rhNGF. One drop six times a day for the entire period
Other: vehicle
Drug page: Recombinant human nerve growth factor
rhNGF 10 μg/ml : one drop 6 times a day (one 35 μl drop equals to 0.35 μg of rhNGF)
Also known as: recombinant human nerve growth factor 10 µg/ml solution
Drug page: Recombinant human nerve growth factor
one drop 6 times a day (one 35 μl drop equals to 0.70 μg of rhNGF)
Also known as: recombinant human nerve growth factor 20 µg/ml solution
ophthalmic solution of the same composition as the test product without rhNGF
Also known as: placebo
Percentage of Patients Achieving Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer
Complete healing of the PED or corneal ulcer was determined by corneal fluorescein staining at 4 weeks as defined by the reading center evaluating the clinical pictures. Complete healing was defined as the greatest diameter of the corneal fluorescein staining in the area of the PED or corneal ulcer being less than 0.5 mm at the Week 4 visit. The primary efficacy variable was analyzed after 4 weeks of treatment only for the Phase II segment of the study. That's why the Phase I groups/arms are not included in this analysis.
Time frame: at 4 weeks of treatment
Percentage of Patients Experiencing Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer
Complete healing of the PED or corneal ulcer at 4 weeks as defined by the Investigator. The complete healing was defined as the greatest diameter of the corneal fluorescein staining in the area of the PED or corneal ulcer, being less than 0.5 mm at the Week 4 visit. This secondary outcome was analyzed after 4 weeks of treatment only for the Phase II segment of the study. That's why the Phase I groups/arms are not included in this analysis.
Time frame: at 4 weeks of study treatment.
Percentage of Patients Experiencing Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer
Complete healing of the PED or corneal ulcer at 6 and 8 weeks measured by both the central reading center and Investigator. Complete healing was defined as the greatest diameter of the corneal fluorescein staining in the area of the PED or corneal ulcer being less than 0.5 mm. This outcome was analyzed after 6 and 8 weeks of treatment only for the Phase II segment of the study. That's why the Phase I groups/arms are not included in this analysis.
Time frame: at 6 and 8 weeks after start of the treatment
Percentage of Patients Experiencing Complete Corneal Clearing
Complete corneal clearing (grade 0 on the modified Oxford scale) at 4, 6 and 8 weeks. A patient was considered to have achieved complete corneal clearing if he/she had a Modified Oxford Scale recorded as Grade 0. The scale has the following grades: 0-1-2-3-4-5, where 5 represents the worst outcome value and 0 the best outcome value.
Time frame: at 4, 6 and 8 weeks after start of the treatment
Mean Change in Best Corrected Distance Visual Acuity (BCDVA)
Mean changes in Best-Corrected Distance Visual Acuity (BCDVA) from baseline to Week 8 are calculated as Least Square means. BCDVA consists of letters read at 4 meters only. Patients are scored by how many letters could be correctly identified. Therefore the higher the number of letters, the higher the visual acuity.
Time frame: At screening and at week 8
Percentage of Patients That Achieve an Improvement in Corneal Sensitivity
Percentage of patients that achieve an improvement in corneal sensitivity as measured by the Cochet-Bonnet aesthesiometer
Time frame: at 4, 6 and 8 weeks.
Percentage of Patients Experiencing Deterioration in Stage 2 or 3 NK
Percentage of patients experiencing deterioration (increase in lesion size ≥ 1mm, decrease in BCDVA by \>5 ETDRS letters, progression in lesion depth to corneal melting or perforation, onset of infection) in stage 2 or 3 NK from baseline to Week 4, 6, and 8.
Time frame: from baseline to Week 4, 6, and 8.
Percentage of Patients Achieving Complete Healing of the PED or Corneal Ulcer by Week 8/16 That Remain Healed at Weeks 20/28, 32/40, 44/52, 56/64
Percentage of patients achieving complete healing of the PED or corneal ulcer by Week 8/16 that remain healed (ie, no recurrence of the PED and/or corneal ulcer) at Weeks 20/28, 32/40, 44/52, 56/64
Time frame: at week 20/28, 32/40, 44/52, and 56/64
Percentage of Patients Experiencing a Different Level of Efficacy at 4 and 8 Weeks
Global evaluation of efficacy as assessed by the Investigator at 4 and 8 weeks. The different level of efficacy were: very good; good; moderate; poor; non-evaluable.
Time frame: at week 4 and 8
Change From Baseline in Visual Analogue Scale (VAS) for Ocular Tolerability
Ocular tolerability was recorded by the patient on a VAS scale from 0 to 100 mm, where a higher VAS score indicates worse ocular symptoms (0 means no symptoms and 100 means the worst possible discomfort). The overall VAS score for ocular tolerability was calculated as the mean of the individual VAS scores for the 7 different symptoms (foreign body sensation, burning/stinging, itching, ocular pain, sticky feeling, blurred vision and photophobia). Results are below reported as per symptoms at week 8 (for treatment period) and week 20 (for Follow Up period).
Time frame: at baseline and at weeks 8 and 20
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA)
Best-Corrected Distance Visual Acuity (BCDVA) by means of the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity chart at 4 meters (13 feet). Data reported refers to week n° 8 (treatment group) and n°12/20 (FU group).
Time frame: at baseline and at period 1 (8 weeks) and 2 (Follow Up period of 12 weeks, until week 20)
Change From Baseline in Intraocular Pressure (IOP)
IOP was measured using a Goldmann applanation tonometer, a handheld applanation tonometer \[eg, Tonopen\], or other tonometer, after the instillation of a topical anesthetic.
Time frame: Baseline, period 1 (8 weeks) and 2 (Follow Up period of 12 weeks, until week 20).
Percentage of Participants With Abnormal Eye Structures by Dilated Fundus Ophthalmoscopy
Dilated fundus ophthalmoscopy was performed to assess the vitreous, retina, macula, choroid and optic nerve head after dilation of the pupil. Percentage of patients is summarized for each eye structure by treatment and visit for the controlled treatment period for Phase I and Phase II separately. The assessment time points were Baseline, weeks 2, 4 and 8 for Phase 1; Baseline and week 8 for Phase 2; and weeks 12 and 56 for follow up. Only results for eye structure at week 8 are reported.
Time frame: At week 8 (Phase 1 and Phase 2)
Percentage of Patients That Achieved a ≥15 Letter Gain in BCDVA
Percentage of patients that achieved a ≥15 letter gain in best corrected distance visual acuity (BCDVA) at 4, 6, and 8 weeks
Time frame: at 4, 6 and 8 weeks
The study consisted of 2 periods: 8week PhaseI/controlled treatment period and 48/56-week FU period. In the Phase1 patients were randomized into 2 cohorts (of 9 pts each). In phase 2 pts were randomized in a 1:1:1 ratio (52 pts each group). Data refer to the 1st database lock when the last patient in Phase2 had completed 12 weeks of FU period.
| Milestone | 1_rhNGF 10µg/ml Phase 1_treatment | 2_rhNGF 20 µg/ml_Phase 1_treatment | 3_vehicle group_Phase 1_treatment | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment |
|---|---|---|---|---|---|---|
| Started | 7 | 7 | 4 | 52 | 52 | 52 |
| Completed | 6 | 6 | 2 | 45 | 39 | 48 |
| Not completed | 1 | 1 | 2 | 7 | 13 | 4 |
| Withdrew: Decision unrelated to adverse event | 0 | 0 | 0 | 1 | 1 | 1 |
| Withdrew: Lack of efficacy | 0 | 0 | 0 | 2 | 1 | 0 |
| Withdrew: Withdrawal by subject | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Adverse event | 1 | 0 | 2 | 3 | 9 | 1 |
| Withdrew: Other causes | 0 | 0 | 0 | 1 | 2 | 2 |
| Milestone | 1_rhNGF 10µg/ml Phase 1_treatment | 2_rhNGF 20 µg/ml_Phase 1_treatment | 3_vehicle group_Phase 1_treatment | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment |
|---|---|---|---|---|---|---|
| Started | 6 | 6 | 2 | 45 | 39 | 48 |
| Completed | 5 | 5 | 1 | 12 | 13 | 15 |
| Not completed | 1 | 1 | 1 | 33 | 26 | 33 |
| Withdrew: Still in study after week 20 | 0 | 0 | 0 | 25 | 23 | 25 |
| Withdrew: Parent withdrew the consent to continue | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Lack of efficacy | 0 | 0 | 0 | 0 | 0 | 1 |
| Withdrew: Adverse event | 1 | 0 | 0 | 5 | 0 | 1 |
| Withdrew: Lost to follow-up | 0 | 0 | 1 | 2 | 0 | 1 |
| Withdrew: Other causes | 0 | 0 | 0 | 1 | 3 | 5 |
Complete healing of the PED or corneal ulcer was determined by corneal fluorescein staining at 4 weeks as defined by the reading center evaluating the clinical pictures. Complete healing was defined as the greatest diameter of the corneal fluorescein staining in the area of the PED or corneal ulcer being less than 0.5 mm at the Week 4 visit. The primary efficacy variable was analyzed after 4 weeks of treatment only for the Phase II segment of the study. That's why the Phase I groups/arms are not included in this analysis.
| percentage of subjects | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment |
|---|---|---|---|
| Yes | 55 | 58 | 20 |
| No | 45 | 42 | 80 |
Complete healing of the PED or corneal ulcer at 4 weeks as defined by the Investigator. The complete healing was defined as the greatest diameter of the corneal fluorescein staining in the area of the PED or corneal ulcer, being less than 0.5 mm at the Week 4 visit. This secondary outcome was analyzed after 4 weeks of treatment only for the Phase II segment of the study. That's why the Phase I groups/arms are not included in this analysis.
| percentage of subjects | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment |
|---|---|---|---|
| Yes | 52 | 61 | 26 |
| No | 48 | 39 | 74 |
Complete healing of the PED or corneal ulcer at 6 and 8 weeks measured by both the central reading center and Investigator. Complete healing was defined as the greatest diameter of the corneal fluorescein staining in the area of the PED or corneal ulcer being less than 0.5 mm. This outcome was analyzed after 6 and 8 weeks of treatment only for the Phase II segment of the study. That's why the Phase I groups/arms are not included in this analysis.
| percentage of subjects | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment |
|---|---|---|---|
| week 6 - central reading center - yes | 68 | 60 | 66 |
| week 6 - central reading center - no | 32 | 40 | 34 |
| week 6 - investigator - yes | 61 | 64 | 41 |
| week 6 - investigator - no | 39 | 36 | 59 |
| week 8 - central reading center - yes | 78 | 83 | 56 |
| week 8 - central reading center - no | 22 | 17 | 44 |
| week 8 - investigator - yes | 79 | 79 | 53 |
| week 8 - investigator - no | 21 | 21 | 47 |
Complete corneal clearing (grade 0 on the modified Oxford scale) at 4, 6 and 8 weeks. A patient was considered to have achieved complete corneal clearing if he/she had a Modified Oxford Scale recorded as Grade 0. The scale has the following grades: 0-1-2-3-4-5, where 5 represents the worst outcome value and 0 the best outcome value.
| percentage of subjects | 1_rhNGF10_Phase 1_treatment | 2_rhNGF20_Phase 1_treatment | 3_vehicle group_Phase 1_treatment | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment |
|---|---|---|---|---|---|---|
| week 4 - yes | 0 | 17 | 33 | 21 | 20 | 7 |
| week 4 - no | 100 | 83 | 67 | 79 | 80 | 93 |
| week 6 - yes | 17 | 14 | 0 | 24 | 23 | 8 |
| week 6 - no | 83 | 86 | 100 | 76 | 77 | 92 |
| week 8 -yes | 17 | 14 | 0 | 27 | 21 | 10 |
| week 8 - no | 83 | 86 | 100 | 73 | 79 | 90 |
Mean changes in Best-Corrected Distance Visual Acuity (BCDVA) from baseline to Week 8 are calculated as Least Square means. BCDVA consists of letters read at 4 meters only. Patients are scored by how many letters could be correctly identified. Therefore the higher the number of letters, the higher the visual acuity.
| LogMAR | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment |
|---|---|---|---|
| Mean Change in Best Corrected Distance Visual Acuity (BCDVA) | 15.8 ± 2.58 | 11.9 ± 2.80 | 6.9 ± 2.83 |
Percentage of patients that achieve an improvement in corneal sensitivity as measured by the Cochet-Bonnet aesthesiometer
| percentage of subjects | 1_rhNGF10_Phase 1_treatment | 2_rhNGF20_Phase 1_treatment | 3_vehicle group_Phase 1_treatment | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment |
|---|---|---|---|---|---|---|
| week 4 - yes | 67 | 50 | 50 | 69 | 61 | 63 |
| week 4 - no | 33 | 50 | 50 | 31 | 39 | 37 |
| week 6 - yes | 67 | 50 | 50 | 83 | 68 | 55 |
| week 6 - no | 33 | 50 | 50 | 17 | 32 | 45 |
| week 8 -yes | 67 | 60 | 100 | 79 | 76 | 68 |
| week 8 - no | 33 | 40 | 0 | 21 | 24 | 32 |
Percentage of patients experiencing deterioration (increase in lesion size ≥ 1mm, decrease in BCDVA by \>5 ETDRS letters, progression in lesion depth to corneal melting or perforation, onset of infection) in stage 2 or 3 NK from baseline to Week 4, 6, and 8.
| percentage of subjects | 1_rhNGF10_Phase 1_treatment | 2_rhNGF20_Phase 1_treatment | 3_vehicle group_Phase 1_treatment | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment |
|---|---|---|---|---|---|---|
| week 4 - yes | 0 | 0 | 0 | 2 | 2 | 5 |
| week 4 - no | 100 | 100 | 100 | 98 | 98 | 95 |
| week 6 - yes | 0 | 0 | 0 | 2 | 0 | 10 |
| week 6 - no | 100 | 100 | 100 | 98 | 100 | 90 |
| week 8 -yes | 0 | 14 | 0 | 4 | 7 | 15 |
| week 8 - no | 100 | 86 | 100 | 96 | 93 | 85 |
Percentage of patients achieving complete healing of the PED or corneal ulcer by Week 8/16 that remain healed (ie, no recurrence of the PED and/or corneal ulcer) at Weeks 20/28, 32/40, 44/52, 56/64
| percentage of subjects | 1_rhNGF10_Phase 1_treatment | 2_rhNGF20_Phase 1_treatment | 3_vehicle group_Phase 1_treatment | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment |
|---|---|---|---|---|---|---|
| week 20/28 - yes | 100 | 75 | 100 | 87 | 89 | 100 |
| week 20/28 - no | 0 | 25 | 0 | 13 | 11 | 0 |
| week 32/40 - yes | 100 | 75 | 100 | 78 | 92 | 100 |
| week 32/40 - no | 0 | 25 | 0 | 22 | 8 | 0 |
| week 44/52 - yes | 100 | 80 | 100 | 67 | 88 | 100 |
| week 44/52 - no | 0 | 20 | 0 | 33 | 12 | 0 |
| week 56/64 - yes | 100 | 80 | 100 | 67 | 82 | 100 |
| week 56/64 - no | 0 | 20 | 0 | 33 | 18 | 0 |
Global evaluation of efficacy as assessed by the Investigator at 4 and 8 weeks. The different level of efficacy were: very good; good; moderate; poor; non-evaluable.
| percentage of subjects | 1_rhNGF10_Phase 1_treatment | 2_rhNGF20_Phase 1_treatment | 3_vehicle group_Phase 1_treatment | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment |
|---|---|---|---|---|---|---|
| week 4 - very good | 17 | 29 | 67 | 40 | 34 | 26 |
| week 4 - good | 33 | 43 | 0 | 38 | 49 | 35 |
| week 4 - moderate | 17 | 0 | 0 | 15 | 7 | 21 |
| week 4 - poor | 33 | 29 | 0 | 6 | 10 | 19 |
| week 4 - non-evaluable | 0 | 0 | 33 | 2 | 0 | 0 |
| week 8 - very good | 17 | 29 | 50 | 48 | 40 | 40 |
| week 8 - good | 33 | 43 | 50 | 31 | 45 | 20 |
| week 8 - moderate | 33 | 0 | 0 | 12 | 5 | 12 |
| week 8 - poor | 17 | 29 | 0 | 4 | 10 | 28 |
| week 8 - non-evaluable | 0 | 0 | 0 | 4 | 0 | 0 |
Ocular tolerability was recorded by the patient on a VAS scale from 0 to 100 mm, where a higher VAS score indicates worse ocular symptoms (0 means no symptoms and 100 means the worst possible discomfort). The overall VAS score for ocular tolerability was calculated as the mean of the individual VAS scores for the 7 different symptoms (foreign body sensation, burning/stinging, itching, ocular pain, sticky feeling, blurred vision and photophobia). Results are below reported as per symptoms at week 8 (for treatment period) and week 20 (for Follow Up period).
| VAS score | 1_rhNGF10_Phase 1_treatment | 2_rhNGF20_Phase 1_treatment | 3_vehicle group_Phase 1_treatment | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment | 1_rhNGF10_Phase 1_FU | 2_rhNGF20_Phase 1_FU | 3_vehicle group_Phase 1_FU | 4_rhNGF10_Phase 2_FU | 5_rhNGF20_Phase 2_FU | 6_vehicle_Phase 2_FU |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Foreign Body Sensation_Baseline | 50.4 ± 25.68 | 24 ± 19.76 | 20.5 ± 29.23 | 34.8 ± 29.4 | 35.4 ± 34.79 | 37.7 ± 36.49 | 50.4 ± 25.68 | 24 ± 19.76 | 20.5 ± 29.23 | 34.8 ± 29.4 | 35.4 ± 34.79 | 37.7 ± 36.49 |
| Foreign Body Sensation_CFB | -21.2 ± 25.96 | -12.9 ± 17.03 | -16 ± 65.05 | -8.8 ± 34.68 | -16.5 ± 36.87 | -20.9 ± 35.86 | -20 ± 30.32 | -13 ± 25.3 | -52 ± 0 | -16.6 ± 31.26 | -22.4 ± 38.77 | -20.7 ± 30.57 |
| burning/stinging_baseline | 41.4 ± 30.85 | 30.7 ± 38.78 | 18 ± 28.57 | 32.5 ± 32.88 | 26.5 ± 30.86 | 30.2 ± 32.21 | 41.4 ± 30.85 | 30.7 ± 38.78 | 18 ± 28.57 | 32.5 ± 32.88 | 26.5 ± 30.86 | 30.2 ± 32.21 |
| burning/stinging_CFB | -14.7 ± 38.02 | -12.1 ± 28.27 | -28.5 ± 23.33 | -3.8 ± 42.13 | -2.5 ± 26.76 | -18 ± 32.97 | -18 ± 41.65 | -16.5 ± 17.13 | -12 ± 0 | -14.9 ± 40.35 | -10.8 ± 31.51 | -14.7 ± 37.54 |
| itching_baseline | 17 ± 27.4 | 18.7 ± 19.62 | 7.8 ± 15.5 | 24.1 ± 27.48 | 21.8 ± 28.68 | 22.9 ± 28.43 | 17 ± 27.4 | 18.7 ± 19.62 | 7.8 ± 15.5 | 24.1 ± 27.48 | 21.8 ± 28.68 | 22.9 ± 28.43 |
| itching_CFB | -3 ± 17.93 | -10 ± 23.1 | -15.5 ± 21.92 | -10.8 ± 29.25 | -7.3 ± 22.67 | -8.9 ± 25.59 | -7.8 ± 27.18 | -4.2 ± 28.51 | -31 ± 0 | -10.2 ± 30.62 | -11.9 ± 23.05 | -4.8 ± 30.71 |
| ocular pain_baseline | 34.1 ± 36.96 | 33.6 ± 34.73 | 19 ± 38 | 32.8 ± 34.86 | 21.1 ± 28.38 | 28.8 ± 32.82 | 34.1 ± 36.96 | 33.6 ± 34.73 | 19 ± 38 | 32.8 ± 34.86 | 21.1 ± 28.38 | 28.8 ± 32.82 |
| ocular pain_CFB | -21.2 ± 28.96 | -6 ± 30.72 | -23 ± 32.53 | -2 ± 43 | 2 ± 37.25 | -16.3 ± 30.52 | -16 ± 28.59 | -9.3 ± 11.86 | -26 ± 0 | -16.7 ± 34.66 | -12.1 ± 31.25 | -18.3 ± 34.3 |
| sticky feeling_baseline | 47.6 ± 34.14 | 32.1 ± 35.34 | 15.5 ± 23.69 | 26.6 ± 29.65 | 17.4 ± 22.07 | 26.1 ± 31.93 | 47.6 ± 34.14 | 32.1 ± 35.34 | 15.5 ± 23.69 | 26.6 ± 29.65 | 17.4 ± 22.07 | 26.1 ± 31.93 |
| sticky feeling_CFB | -7.2 ± 42.82 | -18.7 ± 38.32 | -11 ± 5.66 | -11.7 ± 30.17 | -4.3 ± 29.55 | -10.7 ± 29.95 | -19.8 ± 22.18 | -0.7 ± 12.52 | -2 ± 0 | -13.3 ± 30.75 | -11.4 ± 31.11 | -8.3 ± 30.62 |
| blurred vision_baseline | 71 ± 38.37 | 85.7 ± 14.74 | 93.5 ± 7.9 | 80.2 ± 25.18 | 83.2 ± 24.45 | 78.5 ± 24.68 | 71 ± 38.37 | 85.7 ± 14.74 | 93.5 ± 7.9 | 80.2 ± 25.18 | 83.2 ± 24.45 | 78.5 ± 24.68 |
| blurred vision_CFB | -25.7 ± 34.37 | -25 ± 32.15 | -22 ± 31.11 | -24.9 ± 35.33 | -26.2 ± 31.58 | -17.4 ± 28.55 | -26.5 ± 31.18 | -26.2 ± 17.93 | -14 ± 0 | -16.5 ± 38.42 | -25.7 ± 34.41 | -17.4 ± 27.14 |
| photophobia_baseline | 64.7 ± 42.9 | 66.6 ± 29.85 | 30.3 ± 26.21 | 64.3 ± 32.07 | 57.6 ± 36.1 | 65.2 ± 34.71 | 64.7 ± 42.9 | 66.6 ± 29.85 | 30.3 ± 26.21 | 64.3 ± 32.07 | 57.6 ± 36.1 | 65.2 ± 34.71 |
| photophobia_CFB | -19.5 ± 27.98 | -20.7 ± 34.13 | -30.5 ± 43.13 | -17.8 ± 41.23 | -13.2 ± 40.44 | -17.5 ± 29.02 | -20.3 ± 28.63 | -26 ± 39.88 | -61 ± 0 | -24.2 ± 37.51 | -21 ± 38.76 | -14.6 ± 29.19 |
Best-Corrected Distance Visual Acuity (BCDVA) by means of the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity chart at 4 meters (13 feet). Data reported refers to week n° 8 (treatment group) and n°12/20 (FU group).
| Number of ETDRS letters | 1_rhNGF10_Phase 1_treatment | 2_rhNGF20_Phase 1_treatment | 3_vehicle group_Phase 1_treatment | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment | 1_rhNGF10_Phase 1_FU | 2_rhNGF20_Phase 1_FU | 3_vehicle group_Phase 1_FU | 4_rhNGF10_Phase 2_FU | 5_rhNGF20_Phase 2_FU | 6_vehicle_Phase 2_FU |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline | 42 ± 28.25 | 30.4 ± 24.85 | 9.5 ± 11.96 | 30.7 ± 28.35 | 24.2 ± 25.88 | 32.4 ± 26.07 | 42 ± 28.25 | 30.4 ± 24.85 | 9.5 ± 11.96 | 30.7 ± 28.35 | 24.2 ± 25.88 | 32.4 ± 26.07 |
| Change from baseline | 9.3 ± 5.89 | 8.7 ± 12.41 | -1 ± 1.41 | 15.8 ± 16.82 | 11.9 ± 20.9 | 6.9 ± 15.44 | 11.2 ± 7.47 | 7 ± 9.8 | -6 ± 0 | 13.2 ± 16.8 | 14.2 ± 19.6 | 8.8 ± 14.27 |
IOP was measured using a Goldmann applanation tonometer, a handheld applanation tonometer \[eg, Tonopen\], or other tonometer, after the instillation of a topical anesthetic.
| mmHg | 1_rhNGF10_Phase 1_treatment | 2_rhNGF20_Phase 1_treatment | 3_vehicle group_Phase 1_treatment | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment | 1_rhNGF10_Phase 1_FU | 2_rhNGF20_Phase 1_FU | 3_vehicle group_Phase 1_FU | 4_rhNGF10_Phase 2_FU | 5_rhNGF20_Phase 2_FU | 6_vehicle_Phase 2_FU |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline | 16.1 ± 3.85 | 11.3 ± 3.68 | 11.8 ± 3.3 | 14.3 ± 3.16 | 14 ± 3.06 | 14.1 ± 3.16 | 16.1 ± 3.85 | 11.3 ± 3.68 | 11.8 ± 3.3 | 14.3 ± 3.16 | 14 ± 3.06 | 14.1 ± 3.16 |
| Change from baseline | -1.8 ± 2.48 | 1.9 ± 5.24 | 3.5 ± 2.12 | -0.1 ± 3.71 | 0.9 ± 2.61 | 0.8 ± 3.43 | -2.2 ± 2.49 | 2.3 ± 3.78 | -3 ± 0 | 0.2 ± 3.25 | 0.1 ± 3.64 | 0.6 ± 3.93 |
Dilated fundus ophthalmoscopy was performed to assess the vitreous, retina, macula, choroid and optic nerve head after dilation of the pupil. Percentage of patients is summarized for each eye structure by treatment and visit for the controlled treatment period for Phase I and Phase II separately. The assessment time points were Baseline, weeks 2, 4 and 8 for Phase 1; Baseline and week 8 for Phase 2; and weeks 12 and 56 for follow up. Only results for eye structure at week 8 are reported.
| percentage of participants | 1_rhNGF10_Phase 1_treatment | 2_rhNGF20_Phase 1_treatment | 3_vehicle group_Phase 1_treatment | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment |
|---|---|---|---|---|---|---|
| Vitreous | 0 | 0 | 0 | 14.7 | 18.2 | 10.3 |
| Retina macula | 25 | 25 | 100 | 17.6 | 23.3 | 28.6 |
| Choroid | 0 | 25 | 0 | 8.8 | 6.5 | 14.8 |
| Optic nerve | 25 | 0 | 100 | 11.8 | 12.5 | 7.7 |
Percentage of patients that achieved a ≥15 letter gain in best corrected distance visual acuity (BCDVA) at 4, 6, and 8 weeks
| percentage of subjects | 1_rhNGF10_Phase 1_treatment | 2_rhNGF20_Phase 1_treatment | 3_vehicle group_Phase 1_treatment | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment |
|---|---|---|---|---|---|---|
| week 4 - yes | 0 | 29 | 0 | 37 | 34 | 21 |
| week 4 - no | 100 | 71 | 100 | 63 | 66 | 79 |
| week 6 - yes | 17 | 43 | 0 | 44 | 38 | 28 |
| week 6 - no | 83 | 57 | 100 | 56 | 62 | 72 |
| week 8 -yes | 17 | 43 | 0 | 50 | 42 | 22 |
| week 8 - no | 83 | 57 | 100 | 50 | 58 | 78 |
Collected over Adverse events were collected at each time point of Phase I and Phase II of the study. Phase I: Days 1, 2, Weeks 1, 2, 3, 4, 6, Day 55, Week 8 Phase II: Weeks 1, 2, 3, 4, 6, 8. Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 1_rhNGF10_Phase 1 | 0/7 (0%) | 3/7 (42.9%) | 3/7 (42.9%) |
| 2_rhNGF20_Phase 1 | 0/7 (0%) | 1/7 (14.3%) | 5/7 (71.4%) |
| 3_vehicle group_Phase 1 | 0/4 (0%) | 3/4 (75%) | 1/4 (25%) |
| 4_rhNGF10_Phase 2_treatment | 5/52 (9.6%) | 13/52 (25%) | 23/52 (44.2%) |
| 5_rhNGF20_Phase 2_treatment | 2/52 (3.8%) | 14/52 (26.9%) | 23/52 (44.2%) |
| 6_vehicle group_Phase 2_treatment | 1/52 (1.9%) | 4/52 (7.7%) | 21/52 (40.4%) |
| Event | 1_rhNGF10_Phase 1 | 2_rhNGF20_Phase 1 | 3_vehicle group_Phase 1 | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment |
|---|---|---|---|---|---|---|
| disease progressionGeneral disorders | 2/7 | 0/7 | 1/4 | 1/52 | 3/52 | 2/52 |
| Femur fractureInjury, poisoning and procedural complications | 0/7 | 0/7 | 1/4 | 0/52 | 0/52 | 1/52 |
| renal failureRenal and urinary disorders | 0/7 | 0/7 | 1/4 | 0/52 | 0/52 | 0/52 |
| Pulmonary edemaRespiratory, thoracic and mediastinal disorders | 0/7 | 0/7 | 1/4 | 0/52 | 0/52 | 0/52 |
| visual acuity reducedEye disorders | 1/7 | 0/7 | 0/4 | 0/52 | 2/52 | 1/52 |
| myocardial infarctionCardiac disorders | 0/7 | 1/7 | 0/4 | 2/52 | 0/52 | 0/52 |
| Renal colicRenal and urinary disorders | 0/7 | 0/7 | 0/4 | 0/52 | 2/52 | 0/52 |
| ArrhythmiaCardiac disorders | 0/7 | 0/7 | 0/4 | 1/52 | 0/52 | 0/52 |
| Cardiac failureCardiac disorders | 0/7 | 0/7 | 0/4 | 1/52 | 0/52 | 0/52 |
| Aortic dissectionVascular disorders | 0/7 | 0/7 | 0/4 | 1/52 | 1/52 | 0/52 |
| Event | 1_rhNGF10_Phase 1 | 2_rhNGF20_Phase 1 | 3_vehicle group_Phase 1 | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment |
|---|---|---|---|---|---|---|
| Eye painEye disorders | 0/7 | 3/7 | 1/4 | 2/52 | 7/52 | 5/52 |
| Visual acuity reducedEye disorders | 3/7 | 1/7 | 1/4 | 2/52 | 5/52 | 2/52 |
| PhotophobiaEye disorders | 0/7 | 3/7 | 0/4 | 2/52 | 0/52 | 1/52 |
| Disease progressionGeneral disorders | 2/7 | 0/7 | 1/4 | 4/52 | 4/52 | 6/52 |
| InsomniaPsychiatric disorders | 0/7 | 2/7 | 0/4 | 0/52 | 0/52 | 0/52 |
| headacheNervous system disorders | 0/7 | 2/7 | 0/4 | 2/52 | 4/52 | 2/52 |
| Eye inflammationEye disorders | 0/7 | 2/7 | 1/4 | 0/52 | 1/52 | 0/52 |
| Corneal epithelium defectEye disorders | 0/7 | 2/7 | 0/4 | 1/52 | 5/52 | 1/52 |
| Eyelid margin crustingEye disorders | 0/7 | 0/7 | 1/4 | 0/52 | 0/52 | 0/52 |
| Foreign body sensation in eyesEye disorders | 0/7 | 0/7 | 1/4 | 1/52 | 0/52 | 1/52 |
| Age, Continuous(years) | 1_rhNGF10_Phase 1_treatment | 2_rhNGF20_Phase 1_treatment | 3_vehicle group_Phase 1_treatment | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment | Total |
|---|---|---|---|---|---|---|---|
| Age continuous | 61.7 ± 21.47 | 52.0 ± 17.24 | 64.3 ± 24.06 | 59.0 ± 17.17 | 62.5 ± 14.01 | 60.4 ± 16.78 | 58.5 ± 19.98 |
| Sex: Female, Male(Participants) | 1_rhNGF10_Phase 1_treatment | 2_rhNGF20_Phase 1_treatment | 3_vehicle group_Phase 1_treatment | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment | Total |
|---|---|---|---|---|---|---|---|
| Female | 3 | 4 | 2 | 30 | 30 | 35 | 104 |
| Male | 4 | 3 | 2 | 22 | 22 | 17 | 70 |
| Ethnicity (NIH/OMB)(Participants) | 1_rhNGF10_Phase 1_treatment | 2_rhNGF20_Phase 1_treatment | 3_vehicle group_Phase 1_treatment | 4_rhNGF10_Phase 2_treatment | 5_rhNGF20_Phase 2_treatment | 6_vehicle group_Phase 2_treatment | Total |
|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 0 | 6 | 9 | 5 | 21 |
| Not Hispanic or Latino | 6 | 6 | 4 | 42 | 42 | 41 | 141 |
| Unknown or Not Reported | 0 | 1 | 0 | 4 | 1 | 6 | 12 |
Ran from Jan 2013 to primary completion in Apr 2015, 27 months.
Results were first posted in Jul 2019, 4 years 3 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Feb 2017. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Recombinant human nerve growth factor