Neurotrophic KeratitisPhase 2NCT02227147
Evaluation of Efficacy of 20 µg/ml rhNGF New Formulation (With Anti-oxidant) in Patients With Stage 2 and 3 NK
A Phase 2 study testing rhNGF 20µg/ml in people with Neurotrophic Keratitis, run by Dompé Farmaceutici S.p.A at 12 sites in United States.
Trial summary
The primary objective of this study is to evaluate the efficacy of 20 µg/ml 6 times a day of rhNGF eye drops solution (formulation containing anti-oxidant) compared to vehicle (formulation containing anti-oxidant) given 6 times a day. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neurotrophic Keratitis
- What is being tested?
- rhNGF 20µg/ml
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 12 sitesUnited States
- Study dates
- Feb 2015to Sep 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients 18 years of age or older.
- Patients with stage 2 (persistent epithelial defect, PED) or stage 3 (corneal ulcer) neurotrophic keratitis (NK).
- PED or corneal ulceration of at least 2 weeks duration refractory to one or more conventional non-surgical treatments for neurotrophic keratitis.
- Evidence of decreased corneal sensitivity (≤ 4 cm using the Cochet-Bonnet aesthesiometer) within the area of the PED or corneal ulcer and outside of the area of the defect in at least one corneal quadrant.
- Best corrected distance visual acuity (BCDVA) score ≤ 75 ETDRS (Early Treatment Diabetic Retinopathy Study)letters, (≥ 0.2 LogMAR, ≤ 20/32 Snellen or ≤ 0.625 decimal fraction) in the affected eye(s).
- No objective clinical evidence of improvement in the PED or corneal ulceration within the 2 weeks prior to study enrolment.
- Only patients who satisfy all Informed Consent requirements may be included in the study. The patient and/or his/her legal representative must read, sign and date the Informed Consent document before any study-related procedures are performed. The Informed Consent form signed by patients and/or legal representative must have been approved by the IRB (Institutional Review Board) for the current study.
- Patients must have the ability and willingness to comply with study procedures.
Who cannot join
- Any active ocular infection or active ocular inflammation not related to NK in the affected eye(s).
- Any other ocular disease requiring topical ocular treatment during the course of the study treatment period. No topical treatments other than the study medications provided by the study sponsor and allowed by the study protocol can be administered in the affected eye(s) during the course of the study treatment periods.
- Patients with severe vision loss with no potential for visual improvement in the opinion of the investigator as a result of the study treatment.
- Schirmer test without anesthesia ≤3 mm/5 minutes.
- Patients with severe blepharitis and/or severe meibomian gland disease.
- History of any ocular surgery (including laser or refractive surgical procedures) within the three months before study enrolment. (An exception to the preceding statement will be allowed if the ocular surgery is considered to be the cause of the stage 2 or 3 NK). Ocular surgery will not be allowed during the study treatment period and elective ocular surgery procedures should not be planned during the duration of the follow-up period.
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- Prior surgical procedure(s) for the treatment of NK with the exception of amniotic membrane transplantation. Patients previously treated with amniotic membrane transplantation may only be enrolled two weeks after the membrane has disappeared within the area of the PED or corneal ulcer or at least six weeks after the date of the amniotic membrane transplantation procedure.
- Patients previously treated with Botox injections used to induce pharmacologic blepharoptosis are eligible for enrolment only if the last injection was given at least 90 days prior to enrolment in the study.
- Anticipated need to use therapeutic contact lenses or contact lens wear for refractive correction during the study treatment period in the eye(s) with NK.
- Anticipated need for punctual occlusion during the study treatment period. Patients with punctual occlusion or punctual plugs inserted prior to the study are eligible for enrolment provided that the punctual occlusion is maintained during the study.
- Evidence of corneal ulceration involving the posterior third of the corneal stroma, corneal melting or perforation.
- Presence or history of any ocular or systemic disorder or condition that might hinder the efficacy of the study treatment or its evaluation, could possibly interfere with the interpretation of study results, or could be judged by the investigator to be incompatible with the study visit schedule or conduct.
- Any need for or anticipated change in the dose of systemic medications known to impair the function of the trigeminal nerve. These treatments are allowed during the study if initiated prior study enrolment provided they remain stable throughout the course of the study treatment periods.
- Known hypersensitivity to one of the components of the study or procedural medications (e.g. fluorescein).
- History of drug, medication or alcohol abuse or addiction.
- Use of any investigational agent within 4 weeks of screening visit.
- Participation in another clinical study at the same time as the present study.
- Females of childbearing potential are excluded from participation in the study if they meet any one of the following conditions: are currently pregnant or, have a positive result on the urine pregnancy test at the Randomization Visit or, intend to become pregnant during the study treatment period or, are breast-feeding or are not willing to use highly effective birth control measures.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Tufts Medical Center
Boston, Massachusetts, 02111
Massachusetts Eye & Ear Infirmary
Boston, Massachusetts, 02114
Massachusetts Eye Research and Surgery Institution
Cambridge, Massachusetts, 02451
Baylor College of Medicine
Houston, Texas, 77030
Loma Linda University Ophthalmology
Loma Linda, California, 92354
Jules Stein Eye Institute
Los Angeles, California, 90095
Bascom Palmer Eye Institute University of Miami
Miami, Florida, 33324
New York Eye and Ear Infirmary
New York, New York, 10003
Penn Eye Care Scheie Eye Institute
Philadelphia, Pennsylvania, 19104
UPMC eye center, department of ophthalmology, University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Mayo Clinic
Rochester, Minnesota, 55905
Shiley Eye Center University of California
San Diego, California, 92093
About this study
Official title: An 8-week Phase II, Multicenter, Randomized, Double-masked, Vehicle Controlled Parallel Group Study With a 24 or 32 Week Follow-up to Evaluate the Efficacy of rhNGF 20 µg/ml vs Vehicle in Patients With Stage 2 and 3 Neurotrophic Keratitis
The primary objective of this study is to evaluate the efficacy of 20 µg/ml 6 times a day of rhNGF eye drops solution (formulation containing anti-oxidant) compared to vehicle (formulation containing anti-oxidant) given 6 times a day. The evaluation of efficacy is intended as:
- complete healing of stage 2 (persistent epithelial defect) and 3 (corneal ulcer) neurotrophic keratitis (NK) as measured by the central reading center using corneal fluorescein staining,
- assessing the duration of complete healing,
- improvement in visual acuity and improvement in corneal sensitivity.
Read the detailed description
An 8-week phase II, multicenter, randomized, double-masked, vehicle-controlled, parallel group study with a 24 or 32 week follow-up period to evaluate the efficacy of a formulation containing anti-oxidant of recombinant human nerve growth factor (rhNGF) in 20 μg/ml, eye drops solution versus vehicle containing anti-oxidant in patients with Stage 2 and 3 Neurotrophic Keratitis. The primary objective was to evaluate the efficacy of 20 μg/ml 6 times a day of recombinant human nerve growth factor (rhNGF) containing anti-oxidant, eye drops solution compared to vehicle (formulation containing anti-oxidant) given 6 times a day in inducing a complete healing of stage 2 (PED) and 3 (corneal ulcer) NK as measured by the central reading center, evaluating the clinical pictures of corneal fluorescein staining.
Secondary objectives were to assess the duration of complete healing, improvement in visual acuity and improvement in corneal sensitivity, and percentage of patients achieving complete corneal clearing defined as complete absence of staining on the modified Oxford Scale.
- Conditions
- Neurotrophic Keratitis
- Being tested
- rhNGF 20µg/ml, Placebo
- Keywords
- Neurotrophic Keratitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rhNGF 20µg/mlDrug
Also called cenegermin
PlaceboOther
Also called Vehicle
Formulation containing antioxidant
| Study group | Role | What they receive |
|---|---|---|
| rhNGF 20 µg/ml | Experimental | rhNGF 20 µg/ml eye drops solution, formulation containing anti-oxidant Receives: Drug: rhNGF 20µg/ml |
| Placebo | Placebo comparator | Vehicle: formulation containing anti-oxidant Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by Central Reviewer
Percentage of patients achieving complete healing of the PED or corneal ulcer determined by corneal fluorescein staining at 8 weeks as defined by the central reading center on clinical pictures.
Measured: Week 8
Secondary outcomes (7)
Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by the Investigator
Percentage of patients experiencing complete healing of the PED or corneal ulcer determined by corneal fluorescein staining at 8 weeks as measured by the investigator.
Measured: Week 8
Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by Central Reading Center and Investigator.
Percentage of patients experiencing complete healing of the PED or corneal ulcer at 4, and 6 weeks as measured by the central reading center evaluating the clinical pictures and investigator.
Measured: At weeks 4 and 6
Percentage of Patients With Complete Corneal Clearing
Percentage of patients with complete corneal clearing at weeks 4, 6, and 8 defined as grade 0 on the modified Oxford scale. Grade 0 indicates the absence of conjunctival staining; grade V indicates severe conjunctival staining.
Measured: at weeks 4, 6, and 8
Mean Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA)
Change in Best Corrected Distance Visual Acuity (BCDVA) from baseline to Week 8.
Best Corrected Distance Visual Acuity consists of letters read at 4m only.
Measured: Baseline, Week 8
Percentage of Patients That Achieve a 15 Letter Gain in BCDVA
Percentage of patients that achieve a 15 letter gain in Best Corrected Distance Visual Acuity (BCDVA) at 4 weeks, 6 weeks, 8 weeks
Measured: Weeks 4, week 6 and week 8
Improvement in Corneal Sensitivity
Improvement in corneal sensitivity was measured by the Cochet-Bonnet aesthesiometer at 4, 6 and 8 weeks.
Corneal sensitivity is measured continuously in each patient in cm:
- Area of the Persistent Epithelial Defect (PED) or corneal ulcer
- All quadrants, but outside the PED or corneal ulcer area: Superior nasal, inferior nasal, superior temporal, inferior temporal.
Improvement is defined as an increase of at least 0.5 cm in the location of concern.
Measured: At 4, 6 and 8 weeks after start of the treatment
Patients Experiencing Deterioration
Number of patients experiencing deterioration (increase in lesion size ≥ 1mm and/or decrease in BCDVA by >5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and/or progression in lesion depth to corneal melting or perforation and/or onset of infection) in stage 2 or 3 NK from baseline to Week 8.
Measured: from baseline to Week 8.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2014 (estimated)
- Study startFeb 2015
- Primary completionJun 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neurotrophic KeratitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dompé Farmaceutici S.p.A
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Flavio Mantelli, MD, PhD, Study director, Dompé farmaceutici S.p.A., Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02227147
- Sponsor's protocol ID
- NGF0214
- Status last verified
- Dec 2022
- First submitted
- 26 Aug 2014
- Last updated
- 8 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An 8-week Phase II, Multicenter, Randomized, Double-masked, Vehicle Controlled Parallel Group Study With a 24 or 32 Week Follow-up to Evaluate the Efficacy of rhNGF 20 µg/ml vs Vehicle in Patients With Stage 2 and 3 Neurotrophic Keratitis
- ClinicalTrials.gov ID
- NCT02227147
- Acronym / sponsor ID
- NGF0214
- Conditions
- Neurotrophic Keratitis
- Keywords
- Neurotrophic Keratitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Dompé Farmaceutici S.p.AIndustry (pharma, biotech, devices)
- Study start
- Feb 2015
- Primary completion
- Jun 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 27 Aug 2014 (estimated)
- Results
- Posted 14 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to evaluate the efficacy of 20 µg/ml 6 times a day of rhNGF eye drops solution (formulation containing anti-oxidant) compared to vehicle (formulation containing anti-oxidant) given 6 times a day. The evaluation of efficacy is intended as:
- complete healing of stage 2 (persistent epithelial defect) and 3 (corneal ulcer) neurotrophic keratitis (NK) as measured by the central reading center using corneal fluorescein staining,
- assessing the duration of complete healing,
- improvement in visual acuity and improvement in corneal sensitivity.
Detailed description
An 8-week phase II, multicenter, randomized, double-masked, vehicle-controlled, parallel group study with a 24 or 32 week follow-up period to evaluate the efficacy of a formulation containing anti-oxidant of recombinant human nerve growth factor (rhNGF) in 20 μg/ml, eye drops solution versus vehicle containing anti-oxidant in patients with Stage 2 and 3 Neurotrophic Keratitis. The primary objective was to evaluate the efficacy of 20 μg/ml 6 times a day of recombinant human nerve growth factor (rhNGF) containing anti-oxidant, eye drops solution compared to vehicle (formulation containing anti-oxidant) given 6 times a day in inducing a complete healing of stage 2 (PED) and 3 (corneal ulcer) NK as measured by the central reading center, evaluating the clinical pictures of corneal fluorescein staining.
Secondary objectives were to assess the duration of complete healing, improvement in visual acuity and improvement in corneal sensitivity, and percentage of patients achieving complete corneal clearing defined as complete absence of staining on the modified Oxford Scale.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| rhNGF 20 µg/ml | Experimental | Drug: rhNGF 20µg/mlrhNGF 20 µg/ml eye drops solution, formulation containing anti-oxidant |
| Placebo | Placebo comparator | Other: PlaceboVehicle: formulation containing anti-oxidant |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients 18 years of age or older.
- Patients with stage 2 (persistent epithelial defect, PED) or stage 3 (corneal ulcer) neurotrophic keratitis (NK).
- PED or corneal ulceration of at least 2 weeks duration refractory to one or more conventional non-surgical treatments for neurotrophic keratitis.
- Evidence of decreased corneal sensitivity (≤ 4 cm using the Cochet-Bonnet aesthesiometer) within the area of the PED or corneal ulcer and outside of the area of the defect in at least one corneal quadrant.
- Best corrected distance visual acuity (BCDVA) score ≤ 75 ETDRS (Early Treatment Diabetic Retinopathy Study)letters, (≥ 0.2 LogMAR, ≤ 20/32 Snellen or ≤ 0.625 decimal fraction) in the affected eye(s).
Key exclusion criteria (18 listed)
- Any active ocular infection or active ocular inflammation not related to NK in the affected eye(s).
- Any other ocular disease requiring topical ocular treatment during the course of the study treatment period. No topical treatments other than the study medications provided by the study sponsor and allowed by the study protocol can be administered in the affected eye(s) during the course of the study treatment periods.
- Patients with severe vision loss with no potential for visual improvement in the opinion of the investigator as a result of the study treatment.
- Schirmer test without anesthesia ≤3 mm/5 minutes.
- Patients with severe blepharitis and/or severe meibomian gland disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rhNGF 20µg/mlAlso: cenegermin | Drug | rhNGF 20 µg/ml |
| PlaceboAlso: VehicleFormulation containing antioxidant | Other | Placebo |
Primary outcome
Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by Central Reviewer
Time frame: Week 8
Percentage of patients achieving complete healing of the PED or corneal ulcer determined by corneal fluorescein staining at 8 weeks as defined by the central reading center on clinical pictures.
7 secondary outcomes
Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by the Investigator
Time frame: Week 8
Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by Central Reading Center and Investigator.
Time frame: At weeks 4 and 6
Percentage of Patients With Complete Corneal Clearing
Time frame: at weeks 4, 6, and 8
Mean Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA)
Time frame: Baseline, Week 8
Percentage of Patients That Achieve a 15 Letter Gain in BCDVA
Time frame: Weeks 4, week 6 and week 8
Improvement in Corneal Sensitivity
Time frame: At 4, 6 and 8 weeks after start of the treatment
Patients Experiencing Deterioration
Time frame: from baseline to Week 8.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Flavio Mantelli, MD, PhD study director
Dompé farmaceutici S.p.A., Milan
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rhNGF 20µg/ml in people with Neurotrophic Keratitis, run by Dompé Farmaceutici S.p.A at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Healing of the Persistent Epithelial Defect (PED) or Corneal Ulcer Defined by Central Reviewer (time frame: Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2022.