- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02110225
A Dose Ranging Study to Evaluate the Safety and Potential Efficacy of rhNGF in Patients With Retinitis Pigmentosa (RP) (Lumos)
A 24 Week Phase Ib/II, Multicenter, Randomized, Controlled, Parallel Group, Dose Ranging Study With a 24 Week Follow-up to Evaluate Safety and Potential Efficacy of 2 Doses (60, 180 µg/ml) of rhNGF Solution vs Vehicle in Patients With RP.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Florence, Italy, 50124
- Azienda Ospedaliero Universitaria Careggi
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Milano, Italy, 20142
- Azienda Ospedaliera San Paolo - U.O. Oculistica
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Naples, Italy, 80129
- A.O. Seconda Università Degli Studi di Napoli - Nuovo Policlinico - UOC Oftalmologia
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Rome, Italy, 00168
- Università Cattolica del Sacro Cuore - Policlinico Gemelli - Istituto di Oftalmologia
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Rome, Italy, 00198
- IRCCS Fondazione G.B. Bietti per lo Studio e la Ricerca in Oftalmologia
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients 18 years of age or older.
- Patients with typical forms of RP characterized by the following clinical features: classic fundus appearance (i.e. intraretinal pigment deposits, thinning and atrophy of the retinal pigment epithelium (RPE) in the mid- and far peripheral retina, with relative RPE preservation in the macula, waxy pallor of the optic disc, attenuation of the retinal vessels), reduced and delayed ERG responses, visual field constriction
- Best corrected distance visual acuity (BCDVA) score of ≥ 48 ETDRS letters (equivalent to 20/100 Snellen, +0.7 LogMar, or 0.2 decimal fraction) in either eye at the time of study enrollment.
- Documented evidence of disease progression within the 12 months prior to enrollment in the study as demonstrated by ERG (≥20% decrease in b wave amplitude in scotopic conditions or ≥25% in photopic conditions) and/or visual field testing (≥10% of Goldman Visual Field expressed as area square or ≥3 dB decrease of Humphrey Visual Field Mean Deviation).
- Only patients who satisfy all Informed Consent requirements may be included in the study. The patient and/or his/her impartial witness 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 impartial witness must have been approved by the Ethics Committee (IEC) for the current study.
- Patients must have the ability and willingness to comply with study procedures.
Exclusion Criteria:
- Patients with atypical, early onset (first decade) or syndromic forms of RP (e.g. paravenous, pericentral sector or unilateral RP, Leber's congenital amaurosis, Refsum disease, Usher syndrome, Bardet-Biedl syndrome, etc).
- Patients with non-recordable 30 Hz cone ERG in either eye.
- Patients with Goldman visual field less than 20º using the V4e target or residual central visual field less than -35 dB as evaluated by the 24-2 program of the Humphrey visual field in either eye.
- Evidence of an active ocular infection in either eye.
- History of uveitis or evidence of intraocular inflammation in either eye.
- History or evidence of glaucoma or an intraocular pressure (IOP) greater than or equal 21 mmHg in either eye at the time of study enrollment.
- Patients with foveal thickness ≥ 250 micrometers (as evaluated with OCT).
- History of cystoid macular oedema or presence of cystoid macular oedema on OCT at the time of study enrolment.
- Anterior segment abnormalities or media opacities obscuring the view of the posterior pole in either eye.
- History of any ocular surgery (including laser or refractive surgical procedures) in either eye within the 120 days before study enrolment. 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.
- Treatment with corticosteroids (systemic, periocular or intravitreal) or any other non-approved, experimental, investigational or neuroprotectant therapy (systemic, topical, intravitreal) in either eye within 90 days of study enrollment.
- Use of any medication other than the study medication for the treatment of ocular diseases with the exception of artificial tears during the study period.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: rhNGF 60µg/ml
rhNGF 60 µg/ml eye drops solution, one drop 3 times a day for 24 weeks in both eyes
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rhNGF 60 µg/ml eye drops solution, one drop 3 times a day for 24 weeks in both eyes
Other Names:
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Experimental: rhNGF 180 µg/ml
rhNGF 180 µg/ml eye drops solution, one drop 3 times a day for 24 weeks in both eyes.
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rhNGF 180 µg/ml eye drops solution, one drop 3 times a day for 24 weeks in both eyes
Other Names:
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Placebo Comparator: Vehicle
Placebo eye drops solution, one drop 3 times a day for 24 weeks in both eyes.
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Placebo eye drops solution, one drop 3 times a day for 24 weeks in both eyes
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Serious and Non-Serious Adverse Events
Time Frame: up to 48 weeks
|
Twenty-seven patients of the Safety population experienced at least one treatment-emergent adverse event, 11 patients in the rhNGF 60 μg/ml arm, 13 patients in the rhNGF 180 μg/ml arm and 3 patients in the vehicle arm.
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up to 48 weeks
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Change in Ocular Tolerability - VAS
Time Frame: Weeks 1, 2, 6, 12, 24
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A global ocular discomfort score was determined using a 100 mm Visual Analogue Scale (VAS) on which 0 means no symptoms and 100 means the worst possible discomfort. Specific ocular symptoms to be assessed with the VAS included: foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision, photophobia. For ocular tolerability analysis, mixed models for repeated measures were applied using various ocular tolerability parameters as response variable, treatment, visit and treatment by visit interaction as fixed effects, and baseline value as covariate. |
Weeks 1, 2, 6, 12, 24
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Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart)
Time Frame: Weeks 1, 2, 6, 12, 24, 36, 48
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Best-Corrected Distance Visual Acuity (BCDVA) was assessed for each eye at each visit using an ETDRS visual acuity chart at 4 meters.
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Weeks 1, 2, 6, 12, 24, 36, 48
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Change in Intraocular Pressure (IOP)
Time Frame: Weeks 2,12 and 24
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Intraocular Pressure was measured using either Goldmann applanation tonometry or a handheld applanation tonometer (e.g.
Tonopen) after the instillation of a topical anesthetic.IOP was assessed for each eye at day 0 and at week 2, 12 and 24
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Weeks 2,12 and 24
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Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination
Time Frame: Day 0; Weeks 1, 2, 6, 12, 24, 36 and 48
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Slit Lamp Examination (SLE) (Biomicroscopy) was performed before the instillation of any dilating or anesthetic eye drops or fluorescein agents.
SLE was executed to assess eyelids, lashes, conjunctiva, cornea, lens, iris and anterior chamber.
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Day 0; Weeks 1, 2, 6, 12, 24, 36 and 48
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External Ocular Examination
Time Frame: Day 0, Weeks 1, 2, 6, 12, 24
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External ocular examinations were done to assess, for each eye and at each visit, the motility of extraocular muscles, appearance and function of the eyelids.
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Day 0, Weeks 1, 2, 6, 12, 24
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Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy
Time Frame: Day 0, Weeks 12, 24 and 48
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Dilated fundus ophthalmoscopy was assessed for each eye evaluating the retina, macula, choroid and optic nerve head.
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Day 0, Weeks 12, 24 and 48
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Presence of Anti-NGF Antibodies
Time Frame: At Day 0 and at week 24
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Anti-NGF antibodies tests were performed at screening and at the end of treatment
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At Day 0 and at week 24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Contrast Sensitivity
Time Frame: Weeks 12, 24, 36 and 48
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Contrast sensitivity was assessed using a Mars chart and is expressed as a log contrast sensitivity (log CS) score given by the log CS value at the lowest contrast numeral just prior to two incorrectly identified numerals, minus a scoring correction.
The higher is the number of characters properly read by the patient, the higher is the contrast sensitivity.
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Weeks 12, 24, 36 and 48
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Change From Baseline in Humphrey Visual Field 24-2
Time Frame: Weeks 12, 24, 36 and 48
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The Humphrey Visual Field (HVF) analyzer is a tool for measuring the human visual field by providing information regarding the location of any disease processes or lesion(s) throughout the visual pathway. In particular, Humphrey Visual Field 24-2 was used to assess static perimetry by measuring 24 degrees temporally and 30 degrees nasally and tests 54 points. The Analyser projects a series of white light stimuli of varying intensities (brightness), throughout a uniformly illuminated bowl. The higher is the number of stimuli perceived by the patient, the better is the retina's ability to detect a stimulus at specific points within the visual field. |
Weeks 12, 24, 36 and 48
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Change in Goldmann Visual Field
Time Frame: Weeks 12, 24, 36 and 48
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The Goldmann field exam was performed to assess kinetic perimetry on all enrolled patients.
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Weeks 12, 24, 36 and 48
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Fundus Imaging
Time Frame: Day 0, Weeks 24 and 48
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A recordable fundus image (photo or other electronic format) showing the central 30 degrees was captured through a dilated pupil to document the appearance of the posterior pole.
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Day 0, Weeks 24 and 48
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Ocular Coherence Tomography (OCT)
Time Frame: Day 0, Weeks 12, 24, 36 and 48
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Ocular coherence tomography was performed to evaluate the cross-sectional anatomy of the macula and to document areas of retinal atrophy.
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Day 0, Weeks 12, 24, 36 and 48
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Microperimetry
Time Frame: Day 0, Weeks 12, 24, 36 and 48
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MP1 microperimetry was analyzed to provide a more accurate measurement of retinal sensitivity in the central visual field, even in patients with unstable or extrafoveal fixation.
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Day 0, Weeks 12, 24, 36 and 48
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Binocular Estermann Visual Field
Time Frame: Day 0, Weeks 12, 24, 36 and 48
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Binocular visual field with Estermann grid testing a stimulus array of 120 points spread over an area extending approximately ±75° horizontally, 35° superiorly and 55° inferiorly while the patient looked steadily at the fixation target.
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Day 0, Weeks 12, 24, 36 and 48
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Electrorethinogram (ERG)
Time Frame: Day 0, Weeks 12, 24, 36 and 48
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A full field and 30 Hz flicker ERG was performed according to international standards.
Patients were treated with anesthetic and dilating drops prior to the ERG procedure.
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Day 0, Weeks 12, 24, 36 and 48
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Flavio Mantelli, MD, PhD, Dompé farmaceutici S.p.A., Milan
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- NGF0113
- 2013-003029-26 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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