Evaluation of Safety and Efficacy of rhNGF in Patients With Stage 2 and 3 Neurotrophic Keratitis. (REPARO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Dompé s.p.a.
Sponsor:
Information provided by (Responsible Party):
Dompé s.p.a.
ClinicalTrials.gov Identifier:
NCT01756456
First received: December 20, 2012
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

This study is aimed at assessing the safety and the efficacy of two dose regimens of recombinant human nerve growth factor (rhNGF) eye drops solution compared to vehicle for inducing a complete healing of stage 2 (persistent epithelial defect) and 3 (corneal ulcer) neurotrophic keratitis


Condition Intervention Phase
Neurotrophic Keratitis
Keratitis
Corneal Ulcer
Drug: rhNGF 10 µg/ml eye drops solution
Drug: rhNGF 20 µg/ml eye drops solution
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An 8-week Phase I/II, Multicenter, Randomized, Double-masked, Vehicle Controlled Parallel Group Study With a 48 or 56 Week Follow-up Period to Evaluate the Safety and Efficacy of Two Doses (10 µg/ml and 20 µg/ml) of Recombinant Human Nerve Growth Factor Eye Drops Solution Versus Vehicle in Patients With Stage 2 and 3 of Neurotrophic Keratitis

Resource links provided by NLM:


Further study details as provided by Dompé s.p.a.:

Primary Outcome Measures:
  • Complete healing of the persistent epithelial defect or corneal ulcer [ Time Frame: after 4 weeks of treatment ] [ Designated as safety issue: No ]
    Percentage of patients achieving complete healing of the PED or corneal ulcer determined by corneal fluorescein staining at 4 weeks as defined by the investigator


Secondary Outcome Measures:
  • Percentage of patients experiencing complete healing of the persistent epithelial defect or corneal [ Time Frame: After 6 weeks after start of the treatment ] [ Designated as safety issue: No ]
    Percentage of patients experiencing complete healing of the PED or corneal ulcer at 6 weeks

  • Percentage of patients experiencing complete healing of the persistent epithelial defect or corneal [ Time Frame: After 8 weeks after start of the treatment ] [ Designated as safety issue: No ]
    Percentage of patients experiencing complete healing of the PED or corneal ulcer at 8 weeks

  • Presence of Anti-NGF antibodies [ Time Frame: At screening and at week 8 ] [ Designated as safety issue: Yes ]
    Anti-NGF antibodies and laboratory tests are performed at screening and at the end of treatment and shift tables will be used to present shifts from within/outside the normal range between screening and end of treatment

  • Change in ocular tolerability [ Time Frame: Weeks 2, 4, 6 and 8 ] [ Designated as safety issue: Yes ]
    Ocular tolerability as measured by the visual analogue scale (VAS) will be analyzed by means of analysis of variance, including terms for treatment, time (Weeks 2, 4, 6 and 8), and treatment by time interaction


Estimated Enrollment: 174
Study Start Date: January 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rhNGF 10µg/ml
rhNGF 10 µg/ml eye drops solution, one drop 6 times a day for 8 weeks in the affected eye only
Drug: rhNGF 10 µg/ml eye drops solution
rhNGF 10 µg/ml eye drops solution, one drop 6 times a day for 8 weeks in the affected eye only
Other Name: recombinant human nerve growth factor 10 µg/ml solution
Experimental: rhNGF 20 µg/ml
rhNGF 20 µg/ml eye drops solution, one drop 6 times a day for 8 weeks in the affected eye only
Drug: rhNGF 20 µg/ml eye drops solution
rhNGF 20 µg/ml eye drops solution, one drop 6 times a day for 8 weeks in the affected eye only
Other Name: recombinant human nerve growth factor 20 µg/ml solution
Placebo Comparator: Vehicle
Placebo eye drops solution, one drop 6 times a day for 8 weeks in the affected eye only
Drug: Placebo
Placebo eye drops solution, one drop 6 times a day for 8 weeks in the affected eye only.
Other Name: Vehicle

Detailed Description:

The primary objective of this study is to assess the safety and the efficacy of two dose regimens (10 µg/ml or 20 µg/ml 6 times a day) of recombinant human nerve growth factor (rhNGF) eye drops solution compared to vehicle for inducing a complete healing of stage 2 (persistent epithelial defect) and 3 (corneal ulcer) neurotrophic keratitis (NK) as measured by the investigator using corneal fluorescein staining Secondary objectives of the study are to assess the duration of complete healing, improvement in visual acuity and improvement in corneal sensitivity following treatment with rhNGF eye drops solution

This is a combined phase I/II study. The phase I and II segments of the study will be conducted as an 8 week, randomized, double-masked, vehicle controlled, parallel group study (referred to as the controlled treatment period) followed by a 48 or 56 week follow-up period The design of the phase I and phase II segments of the study are identical with the exception that in the phase I segment of the study the randomization scheme is different and patients will be followed with additional safety assessments and blood samples for PK (pharmacokinetic) profiling In the ascending dose Phase I segment of the study two doses of rhNGF 10 and 20 µg/ml will be evaluated in a sequential manner

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients 18 years of age or older.
  2. Patients with stage 2 (persistent epithelial defect, PED) or stage 3 (corneal ulcer) neurotrophic keratitis involving only one eye. . Patients with Controlateral eye affected with stage 1 NK can be enrolled.
  3. PED or corneal ulceration of at least 2 weeks duration refractory to one or more conventional non-surgical treatments for neurotrophic keratitis (e.g., preservative-free artificial tears, gels or ointments; discontinuation of preserved topical drops and medications that can decrease corneal sensitivity; therapeutic contact lenses).
  4. 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.
  5. Best corrected distance visual acuity (BCDVA) score ≤ 75 ETDRS letters, (≥ 0.2 LogMAR, ≤ 20/32 Snellen or ≤ 0.625 decimal fraction) in the affected eye.
  6. No objective clinical evidence of improvement in the PED or corneal ulceration within the 2 weeks prior to study enrolment.
  7. 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 IEC/IRB for the current study.
  8. Patients must have the ability and willingness to comply with study procedures.
  9. Patients must be eligible for the National Health Insurance (where applicable).

Exclusion Criteria:

  1. Patients with stage 2 or 3 NK affecting both eyes.
  2. Any active ocular infection (bacterial, viral, fungal or protozoal) or active ocular inflammation not related to NK in the affected eye.
  3. Any other ocular disease requiring topical ocular treatment in the affected eye during the course of the study treatment period. No topical treatments other than the study medications provided by the study sponsor or allowed by the study protocol can be administered in the affected eye during the course of the study treatment periods.
  4. Patients with severe vision loss in the affected eye with no potential for visual improvement in the opinion of the investigator as a result of the study treatment.
  5. Schirmer test without anesthesia ≤3 mm/5 minutes in the affected eye.
  6. Patients with severe blepharitis and/or severe meibomian gland disease in the affected eye.
  7. History of any ocular surgery (including laser or refractive surgical procedures) in the affected eye 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 in the affected eye 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.
  8. Prior surgical procedure(s) for the treatment of NK (e.g. complete tarsorraphy, conjunctival flap, etc) in the affected eye 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 (botulinum toxin) 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.
  9. Use of therapeutic contact lenses or contact lens wear for refractive correction during the study treatment periods in the eye with NK.
  10. 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.
  11. Evidence of corneal ulceration involving the posterior third of the corneal stroma, corneal melting or perforation in the affected eye.
  12. 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 (e.g. progressive or degenerative corneal or retinal conditions, uveitis, optic neuritis, poorly controlled diabetes, autoimmune disease, systemic infection, neoplastic diseases).
  13. Any need for or anticipated change in the dose of systemic medications known to impair the function of the trigeminal nerve (e.g. neuroleptics, antipsychotic and antihistamine drugs). These treatments are allowed during the study if initiated prior to 30 days before study enrolment provided they remain stable throughout the course of the study treatment periods.
  14. Known hypersensitivity to one of the components of the study or procedural medications (e.g. fluorescein).
  15. History of drug, medication or alcohol abuse or addiction.
  16. Use of any investigational agent within 4 weeks of screening visit.
  17. Participation in another clinical study at the same time as the present study.
  18. Females of childbearing potential (those who are not surgically sterilized or post-menopausal for at least 1 year) 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 not willing to use highly effective birth control measures, such as: Hormonal contraceptives -oral, implanted, transdermal, or injected and/or Mechanical barrier methods -spermicide in conjunction with a barrier such as a condom or diaphragm or IUD during the entire course of and 30 days after the study treatment periods.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01756456

Contacts
Contact: Isabella Filatori, M.Sc. 00390258383205 isabella.filatori@dompe.it
Contact: Paolo Battigello, M.Sc. 00390258383422 paolo.battigello@dompe.it

  Show 39 Study Locations
Sponsors and Collaborators
Dompé s.p.a.
Investigators
Study Director: Francesco Sinigaglia, MD Dompé s.p.a., Milan
  More Information

No publications provided

Responsible Party: Dompé s.p.a.
ClinicalTrials.gov Identifier: NCT01756456     History of Changes
Other Study ID Numbers: NGF0212, 2012-002527-15
Study First Received: December 20, 2012
Last Updated: June 23, 2014
Health Authority: Belgium: Ethics Committee
Belgium: Federal Agency for Medicinal Products and Health Products
France: Institutional Ethical Committee
Germany: Ethics Commission
Hungary: Institutional Ethics Committee
Italy: Ethics Committee
Italy: The Italian Medicines Agency
Poland: Ethics Committee
Portugal: Health Ethic Committee
Spain: Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Dompé s.p.a.:
Keratitis
Corneal Ulcer

Additional relevant MeSH terms:
Keratitis
Corneal Ulcer
Corneal Diseases
Eye Diseases
Eye Infections
Infection
Pharmaceutical Solutions
Tetrahydrozoline
Mitogens
Ophthalmic Solutions
Therapeutic Uses
Pharmacologic Actions
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nasal Decongestants
Vasoconstrictor Agents
Cardiovascular Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on September 30, 2014