Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Dose Ranging Study to Evaluate the Safety and Potential Efficacy of rhNGF in Patients With Retinitis Pigmentosa (RP) (Lumos)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02110225
Recruitment Status : Completed
First Posted : April 10, 2014
Results First Posted : July 11, 2019
Last Update Posted : July 11, 2019
Sponsor:
Information provided by (Responsible Party):
Dompé Farmaceutici S.p.A

Brief Summary:
The primary objective of the study is to assess the safety and tolerability of two dose regimens of recombinant human nerve growth factor (rhNGF) eye drops solution administered over 6 months versus a vehicle control in patients with typical retinitis pigmentosa. The secondary objective of this study is to attempt to show a dose response by assessing the potential efficacy of the rhNGF dose regimens for improving or slowing the deterioration of visual function outcomes at 3 and 6 months. During a 6 month follow-up period patients will be monitored to determine if there is evidence of a persistent biological effect after discontinuation of the study treatment.

Condition or disease Intervention/treatment Phase
Retinitis Pigmentosa Drug: rhNGF 60 µg/ml eye drops solution Drug: rhNGF 180 µg/ml eye drops solution Drug: Placebo Phase 1 Phase 2

Detailed Description:
This is a 24-week phase Ib/II, multicenter, randomized, double-masked, vehicle controlled, parallel-group, dose-ranging study with a 24-week follow-up period to evaluate the safety and potential efficacy of two doses (60 μg/ml and 180 μg/ml) of recombinant human nerve growth factor (rhNGF) eye drops solution versus vehicle in patients with typical retinitis pigmentosa (RP).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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.
Actual Study Start Date : January 2014
Actual Primary Completion Date : November 2015
Actual Study Completion Date : November 2015


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
Drug: rhNGF 60 µg/ml eye drops solution
rhNGF 60 µg/ml eye drops solution, one drop 3 times a day for 24 weeks in both eyes
Other Name: recombinant human nerve growth factor 60 µg/ml solution

Experimental: rhNGF 180 µg/ml
rhNGF 180 µg/ml eye drops solution, one drop 3 times a day for 24 weeks in both eyes.
Drug: rhNGF 180 µg/ml eye drops solution
rhNGF 180 µg/ml eye drops solution, one drop 3 times a day for 24 weeks in both eyes
Other Name: recombinant human nerve growth factor 180 µg/ml solution

Placebo Comparator: Vehicle
Placebo eye drops solution, one drop 3 times a day for 24 weeks in both eyes.
Drug: Placebo
Placebo eye drops solution, one drop 3 times a day for 24 weeks in both eyes
Other Name: Vehicle




Primary Outcome Measures :
  1. 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.

  2. Change in Ocular Tolerability - VAS [ Time Frame: Weeks 1, 2, 6, 12, 24 ]

    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.


  3. Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart) [ Time Frame: Weeks 1, 2, 6, 12, 24, 36, 48 ]
    Best-Corrected Distance Visual Acuity (BCDVA) was assessed for each eye at each visit using an ETDRS visual acuity chart at 4 meters.

  4. Change in Intraocular Pressure (IOP) [ Time Frame: Weeks 2,12 and 24 ]
    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

  5. 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 ]
    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.

  6. External Ocular Examination [ Time Frame: Day 0, Weeks 1, 2, 6, 12, 24 ]
    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.

  7. Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy [ Time Frame: Day 0, Weeks 12, 24 and 48 ]
    Dilated fundus ophthalmoscopy was assessed for each eye evaluating the retina, macula, choroid and optic nerve head.

  8. Presence of Anti-NGF Antibodies [ Time Frame: At Day 0 and at week 24 ]
    Anti-NGF antibodies tests were performed at screening and at the end of treatment


Secondary Outcome Measures :
  1. Change From Baseline in Contrast Sensitivity [ Time Frame: Weeks 12, 24, 36 and 48 ]
    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.

  2. Change From Baseline in Humphrey Visual Field 24-2 [ Time Frame: Weeks 12, 24, 36 and 48 ]

    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.


  3. Change in Goldmann Visual Field [ Time Frame: Weeks 12, 24, 36 and 48 ]
    The Goldmann field exam was performed to assess kinetic perimetry on all enrolled patients.

  4. Fundus Imaging [ Time Frame: Day 0, Weeks 24 and 48 ]
    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.

  5. Ocular Coherence Tomography (OCT) [ Time Frame: Day 0, Weeks 12, 24, 36 and 48 ]
    Ocular coherence tomography was performed to evaluate the cross-sectional anatomy of the macula and to document areas of retinal atrophy.

  6. Microperimetry [ Time Frame: Day 0, Weeks 12, 24, 36 and 48 ]
    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.

  7. Binocular Estermann Visual Field [ Time Frame: Day 0, Weeks 12, 24, 36 and 48 ]
    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.

  8. Electrorethinogram (ERG) [ Time Frame: Day 0, Weeks 12, 24, 36 and 48 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02110225


Locations
Layout table for location information
Italy
Azienda Ospedaliero Universitaria Careggi
Florence, Italy, 50124
Azienda Ospedaliera San Paolo - U.O. Oculistica
Milano, Italy, 20142
A.O. Seconda Università Degli Studi di Napoli - Nuovo Policlinico - UOC Oftalmologia
Naples, Italy, 80129
Università Cattolica del Sacro Cuore - Policlinico Gemelli - Istituto di Oftalmologia
Rome, Italy, 00168
IRCCS Fondazione G.B. Bietti per lo Studio e la Ricerca in Oftalmologia
Rome, Italy, 00198
Sponsors and Collaborators
Dompé Farmaceutici S.p.A
Investigators
Layout table for investigator information
Study Director: Flavio Mantelli, MD, PhD Dompé farmaceutici S.p.A., Milan

Layout table for additonal information
Responsible Party: Dompé Farmaceutici S.p.A
ClinicalTrials.gov Identifier: NCT02110225     History of Changes
Other Study ID Numbers: NGF0113
2013-003029-26 ( EudraCT Number )
First Posted: April 10, 2014    Key Record Dates
Results First Posted: July 11, 2019
Last Update Posted: July 11, 2019
Last Verified: April 2019

Keywords provided by Dompé Farmaceutici S.p.A:
Cone-Rod Degenerations
Cone-Rod Dystrophy
Cone-Rod Dystrophy 2
Cone-Rod Retinal Dystrophy
Pigmentary Retinopathy
Retinal Cone-Rod Dystrophy
Rod Cone Dystrophies
Rod-Cone Dystrophy
Tapetoretinal Degeneration

Additional relevant MeSH terms:
Layout table for MeSH terms
Retinitis
Retinitis Pigmentosa
Retinal Diseases
Eye Diseases
Eye Diseases, Hereditary
Retinal Dystrophies
Retinal Degeneration
Genetic Diseases, Inborn
Pharmaceutical Solutions
Mitogens
Ophthalmic Solutions
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action