Clinical trial NCT02110225: A Dose Ranging Study to Evaluate the Safety and Potential Efficacy of rhNGF in Patients With Retinitis Pigmentosa (RP)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Retinitis Pigmentosa
Keywords: 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
Lead sponsor: Dompé Farmaceutici S.p.A
Sponsor class: INDUSTRY
First posted: 2014-04-10
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility 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.

Primary outcomes:
measure: Number of Participants With Serious and Non-Serious Adverse Events
timeFrame: up to 48 weeks
measure: Change in Ocular Tolerability - VAS
timeFrame: Weeks 1, 2, 6, 12, 24
measure: Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart)
timeFrame: Weeks 1, 2, 6, 12, 24, 36, 48
measure: Change in Intraocular Pressure (IOP)
timeFrame: Weeks 2,12 and 24
measure: Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination
timeFrame: Day 0; Weeks 1, 2, 6, 12, 24, 36 and 48
measure: External Ocular Examination
timeFrame: Day 0, Weeks 1, 2, 6, 12, 24
measure: Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy
timeFrame: Day 0, Weeks 12, 24 and 48
measure: Presence of Anti-NGF Antibodies
timeFrame: At Day 0 and at week 24
Secondary outcomes:
measure: Change From Baseline in Contrast Sensitivity
timeFrame: Weeks 12, 24, 36 and 48
measure: Change From Baseline in Humphrey Visual Field 24-2
timeFrame: Weeks 12, 24, 36 and 48
measure: Change in Goldmann Visual Field
timeFrame: Weeks 12, 24, 36 and 48
measure: Fundus Imaging
timeFrame: Day 0, Weeks 24 and 48
measure: Ocular Coherence Tomography (OCT)
timeFrame: Day 0, Weeks 12, 24, 36 and 48
measure: Microperimetry
timeFrame: Day 0, Weeks 12, 24, 36 and 48
measure: Binocular Estermann Visual Field
timeFrame: Day 0, Weeks 12, 24, 36 and 48
measure: Electrorethinogram (ERG)
timeFrame: Day 0, Weeks 12, 24, 36 and 48
Other outcomes:
Locations:
city: Florence
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
city: Milano
country: Italy
facility: Azienda Ospedaliera San Paolo - U.O. Oculistica
city: Naples
country: Italy
facility: A.O. Seconda Università Degli Studi di Napoli - Nuovo Policlinico - UOC Oftalmologia
city: Rome
country: Italy
facility: Università Cattolica del Sacro Cuore - Policlinico Gemelli - Istituto di Oftalmologia
city: Rome
country: Italy
facility: IRCCS Fondazione G.B. Bietti per lo Studio e la Ricerca in Oftalmologia
Study officials:
affiliation: Dompé farmaceutici S.p.A., Milan
name: Flavio Mantelli, MD, PhD
role: STUDY_DIRECTOR
References: