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

NCT02110225 | Completed Phase 1 Results DMC

• 2 other identifiers: NGF01132013-003029-26
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

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.

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

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Serious and Non-Serious Adverse Events

  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.

  up to 48 weeks

• Change in Ocular Tolerability - VAS

  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

• Change in Best Corrected Distance Visual Acuity (BCDVA) (ETDRS Chart)

  Best-Corrected Distance Visual Acuity (BCDVA) was assessed for each eye at each visit using an ETDRS visual acuity chart at 4 meters.

  Weeks 1, 2, 6, 12, 24, 36, 48

• Change in Intraocular Pressure (IOP)

  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

  Weeks 2,12 and 24

• Number of Participants With Normal or Abnormal Findings by Slit Lamp Examination

  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.

  Day 0; Weeks 1, 2, 6, 12, 24, 36 and 48

• External Ocular Examination

  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.

  Day 0, Weeks 1, 2, 6, 12, 24

• Change in Ocular Tolerability - Dilated Fundus Ophthalmoscopy

  Dilated fundus ophthalmoscopy was assessed for each eye evaluating the retina, macula, choroid and optic nerve head.

  Day 0, Weeks 12, 24 and 48

• Presence of Anti-NGF Antibodies

  Anti-NGF antibodies tests were performed at screening and at the end of treatment

  At Day 0 and at week 24

Secondary Outcomes (8)

• Change From Baseline in Contrast Sensitivity

  Weeks 12, 24, 36 and 48

• Change From Baseline in Humphrey Visual Field 24-2

  Weeks 12, 24, 36 and 48

• Change in Goldmann Visual Field

  Weeks 12, 24, 36 and 48

• Fundus Imaging

  Day 0, Weeks 24 and 48

• Ocular Coherence Tomography (OCT)

  Day 0, Weeks 12, 24, 36 and 48

Study Arms (3)

rhNGF 60µg/ml

EXPERIMENTAL

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 180 µg/ml

EXPERIMENTAL

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

Vehicle

PLACEBO COMPARATOR

Placebo eye drops solution, one drop 3 times a day for 24 weeks in both eyes.

Drug: Placebo

Interventions

rhNGF 60 µg/ml eye drops solution DRUG

rhNGF 60 µg/ml eye drops solution, one drop 3 times a day for 24 weeks in both eyes

Also known as: recombinant human nerve growth factor 60 µg/ml solution

rhNGF 60µg/ml

rhNGF 180 µg/ml eye drops solution DRUG

rhNGF 180 µg/ml eye drops solution, one drop 3 times a day for 24 weeks in both eyes

Also known as: recombinant human nerve growth factor 180 µg/ml solution

rhNGF 180 µg/ml

Placebo DRUG

Placebo eye drops solution, one drop 3 times a day for 24 weeks in both eyes

Also known as: Vehicle

Vehicle

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead

Study Sites (5)

Azienda Ospedaliero Universitaria Careggi

Florence, 50124, Italy

Location

Azienda Ospedaliera San Paolo - U.O. Oculistica

Milan, 20142, Italy

Location

A.O. Seconda Università Degli Studi di Napoli - Nuovo Policlinico - UOC Oftalmologia

Naples, 80129, Italy

Location

Università Cattolica del Sacro Cuore - Policlinico Gemelli - Istituto di Oftalmologia

Rome, 00168, Italy

Location

IRCCS Fondazione G.B. Bietti per lo Studio e la Ricerca in Oftalmologia

Rome, 00198, Italy

Location

MeSH Terms

Conditions

Retinitis Pigmentosa; Cone-Rod Dystrophies

Interventions

cenegermin; Ophthalmic Solutions; Solutions

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Dystrophies; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pharmaceutical Solutions; Pharmaceutical Preparations; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals

Limitations and Caveats

LImitations and caveats non specified

Results Point of Contact

• Title: Flavio Mantelli, MD, PhD
• Organization: Dompé farmaceutici s.p.a.

clinical.trials@dompe.com

+39 02 583831

Study Officials

• Flavio Mantelli, MD, PhD

  Dompé farmaceutici S.p.A., Milan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2014
• First Posted: April 10, 2014
• Study Start: January 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: April 18, 2024
• Results First Posted: July 11, 2019

Record last verified: 2023-12

Locations

IT (5)