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A Study to Evaluate Safety and Efficacy of rhNGF Eye Solution vs Vehicle in Patients With Moderate to Severe Dry Eye

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ClinicalTrials.gov Identifier: NCT03982368
Recruitment Status : Recruiting
First Posted : June 11, 2019
Last Update Posted : October 28, 2019
Sponsor:
Information provided by (Responsible Party):
Dompé Farmaceutici S.p.A

Tracking Information
First Submitted Date  ICMJE May 23, 2019
First Posted Date  ICMJE June 11, 2019
Last Update Posted Date October 28, 2019
Actual Study Start Date  ICMJE June 10, 2019
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 10, 2019)
Change from baseline in Schirmer I test (without anesthesia) Vs week 4 [ Time Frame: at week 4 ]
Without previously instilling anesthetic drops, the Schirmer strips is inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes. The patients will be instructed to close their eyes gently. After 5 minutes have elapsed, the Schirmer test strip will be removed and the length of the tear absorption on the strip will be measured (millimeters/5 minutes) Cutoff values: <5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03982368 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2019)
  • Change from baseline in Symptoms questionnaire (SANDE) scores for severity Vs week 4 [ Time Frame: at week 4 ]
    The SANDE score is calculated by taking the square root of the product of the severity of symptoms score. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.
  • Change from baseline in Symptoms questionnaire (SANDE) scores for frequency Vs week 4 [ Time Frame: at week 4 ]
    The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score. The SANDE scale ranges from 0 to 100 wi.100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms
  • Change from baseline in Schirmer II test (with anesthesia) Vs week 4; [ Time Frame: at week 4 ]
    The Schirmer II test is performed as the Schirmer I test after instilling anesthetic drops. The Schirmer strips are inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters is recorded after 5 minutes. All patients are seated at rest with their eyes closed, and the lower cul-de-sac is gently dried with a cotton applicator before the placement of strips. Cutoff values: <5 mm - pathologic dry eye 5-10 mm - marginal dry eye >10 and <30 mm - normal secretion
  • Change from baseline in cornea vital staining with fluorescein (National Eye Institute [NEI] scales) Vs week 4 [ Time Frame: at week 4 ]
    The NEI/Industry Workshop guidelines are used for grading the scale of corneal and conjunctival damage. The cornea is divided into five sectors (central, superior, inferior, nasal and temporal), each of which is scored on a scale of 0-3, with a maximal total corneal staining score of 15. Briefly, grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage in the considered sector.
  • Change from baseline in conjunctiva vital staining with fluorescein (National Eye Institute [NEI] scales) Vs week 4; [ Time Frame: at week 4 ]
    The NEI/Industry Workshop guidelines are used for grading the scale of corneal and conjunctival damage. Both nasally and temporally, the conjunctiva is divided into a superior paralimbal area, an inferior paralimbal area, and a peripheral area with a grading scale of 0-3 and with a maximal total score of 9 for the nasal and temporal conjunctiva (overall the total score ranged from 0-18). Briefly, grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage in the considered sector.
  • Change from baseline in Tear Film Break-Up Time (TFBUT) Vs week 4 [ Time Frame: at week 4 ]
    TFBUT is measured by determining the time to tear break-up. The TFBUT is performed after instillation of 5 μL of 2% preservative-free sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye. The patient is instructed to blink several times to thoroughly mix the fluorescein with the tear film. A TFBUT greater than 15 " is considered normal, while a break time of less than 10" is to be considered pathological.
  • Number of patients who experienced a worsening in symptom scores (SANDE) and/or NEI score ≥ 50% assessed at week 4. [ Time Frame: at week 4 ]
    The SANDE score is calculated by taking the square root of the product of the severity of symptoms score. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms. The NEI/Industry Workshop guidelines are used for grading the scale of corneal and conjunctival damage. The cornea is divided into five sectors (central, superior, inferior, nasal and temporal), each of which is scored on a scale of 0-3, with a maximal total corneal staining score of 15. Both nasally and temporally, the conjunctiva is divided into a superior paralimbal area, an inferior paralimbal area, and a peripheral area with a grading scale of 0-3 and with a maximal total score of 9 for the nasal and temporal conjunctiva (overall the total score ranged from 0-18). Briefly, grade 0 reflects normal/healthy situation, whereas grade 3 reflects a severe damage in the considered sector.
  • Quality of life (Impact of Dry Eye on Everyday Life (IDEEL) questionnaire [ Time Frame: at baseline and weeks 4, 8, 12 and 16 ]
    IDEEL assesses quality of life, symptoms and treatment effects on patients with dry eye. The IDEEL contains 3 modules (Daily Activities, Treatment Satisfaction, and Symptom Bother) with a total of 57 questions.
    1. The Daily Activities Module is the quality of life instrument. It is comprised of 27 items.
    2. The IDEEL Treatment Satisfaction and Bother Module is divided into 2 sections, Treatment - In General and Treatment - Eye Drops.
    3. The Symptom Bother Module consists of 20 items in a single content domain, Symptom Bother.
    Scores for each dimensions ranged from 0 to 100. Higher scores for: dimensions of the Dry Eye Impact on Daily Life module indicates less impact on daily activities; Symptom-Bother dimension indicates greater bother due to symptoms; Satisfaction with Treatment Effectiveness dimension indicates greater satisfaction with treatment effectiveness; Treatment-related Bother/Inconvenience indicates less treatment-related bother or inconvenience.
  • Patient global Impression of change (PGIC); [ Time Frame: at baseline and weeks 4, 8, 12 and 16 ]
    PGIC is a commonly used method of assessing clinically important change. With PGIC the qualitative assessment of meaningful change is determined by the patient on 7-items using a 0 (very much improved) to 10 (very much worse) scale.
  • EQ-5D-3L questionnaire [ Time Frame: at baseline and weeks 4, 8, 12 and 16 ]
    EQ-5D is a standardised measure of health status. The EQ-5D 3 level version (EQ-5D-3L) essentially consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems. The respondent is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions. The EQ VAS records the respondent's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. This information can be used as a quantitative measure of health outcome as judged by the individual respondents.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Safety and Efficacy of rhNGF Eye Solution vs Vehicle in Patients With Moderate to Severe Dry Eye
Official Title  ICMJE A 4 Weeks, Phase II, Multicenter, Randomized, Double-masked, Vehicle-controlled, Parallel Group Study With 12 Weeks of Follow-up to Evaluate Safety and Efficacy of rhNGF Eye Drops Solution vs Vehicle in Moderate to Severe Dry Eye.
Brief Summary The primary objective of this study is to assess the efficacy and safety of rhNGF eye drops at 20 μg/ml concentration administered two or three times daily for 4 weeks in patients with moderate to severe dry eye. The trial is designed to perform dose ranging.
Detailed Description

This is a 4 weeks, Phase II, multicenter, randomized, double-masked, vehicle-controlled, parallel group study with 12 weeks of follow-up to evaluate safety and efficacy of recombinant human Nerve Growth Factor (rhNGF) eye drops solution versus vehicle, in patients with moderate to severe dry eye (DE).

Test product is rhNGF 20 μg/ml; reference product is vehicle. Test and reference will be instilled in both eyes according to the following scheme:

Group 1: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours, e.g. 7:00 am, 02:00 pm; 09:00 pm).

Group 2: one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours, e.g. 7:00 am, 02:00 pm; 09:00 pm).

NB: rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.

Group 3: vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours, e.g. 7:00 am, 02:00 pm; 09:00 pm).

Randomization 1:1:1 of 300 patients to rhNGF eye drops solution 20 μg/ml TID (100 patients) or rhNGF eye drops solution 20 μg/ml BID + vehicle eye drop SID (100 patients) or vehicle eye drops solution (100 patients) TID for 4 weeks.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Parallel groups
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double masked
Primary Purpose: Treatment
Condition  ICMJE Dry Eye Syndrome
Intervention  ICMJE
  • Drug: rhNGF 20 μg/ml
    one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)
    Other Name: cenegermin
  • Drug: rhNGF 20 μg/ml + vehicle

    one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours).

    rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.

    Other Name: cenegermin + placebo
  • Other: Vehicle
    one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
    Other Name: placebo
Study Arms  ICMJE
  • Experimental: rhNGF 20 μg/ml TID
    One drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours)
    Intervention: Drug: rhNGF 20 μg/ml
  • Experimental: rhNGF 20 μg/ml BID + vehicle OD
    One drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily (BID) plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (OD) (every 6-8 hours)
    Intervention: Drug: rhNGF 20 μg/ml + vehicle
  • Placebo Comparator: Vehicle TID
    Vehicle eye one drop will be instilled in both eyes three times daily (every 6-8 hours)
    Intervention: Other: Vehicle
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 10, 2019)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female aged ≥ 18 years
  2. Patients with moderate to severe dry eye characterized by the following clinical features:

    1. Corneal and/or conjunctival staining with fluorescein using National Eye Institute (NEI) grading system > 3
    2. SANDE questionnaire >25 mm
    3. Schirmer test I (without anaesthesia) >2mm <10 mm/5 minutes
    4. Tear film break-up time (TFBUT) < 10 seconds in the worse eye
  3. The same eye (eligible eye) must fulfill all the above criteria
  4. Patients diagnosed with dry eye at least 6 months before enrolment (current use or recommended use of artificial tears for the treatment of Dry Eye)
  5. Best corrected distance visual acuity (BCDVA) score of ≥ 0.1 decimal units (20/200 Snellen value) in both eyes at the time of study enrolment
  6. If a female of childbearing potential, have a negative pregnancy test
  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 Institutional Review Board (IRB) / Independent Ethics Committee (IEC) for the current study
  8. Patients must have the ability and willingness to comply with study procedures.

Exclusion Criteria:

  1. Inability to speak and understand the local language sufficiently to understand the nature of the study, to provide written informed consent, and to allow the completion of all study assessments;
  2. Evidence of an active ocular infection, in either eye
  3. Presence of any other ocular disorder or condition requiring topical medication during the entire duration of study
  4. History of severe systemic allergy or of ocular allergy (including seasonal conjunctivitis) or chronic conjunctivitis and/or keratitis other than dry eye
  5. Intraocular inflammation defined as Tyndall score >0
  6. History of malignancy in the last 5 years
  7. Systemic disease not stabilized within 1 month before Screening Visit (e.g. diabetes with glycemia out of range, thyroid malfunction..) or judged by the investigator to be incompatible with the study (e.g. current systemic infections) or with a condition incompatible with the frequent assessment required by the study
  8. Patient had a serious adverse reaction or significant hypersensitivity to any drug or chemically related compounds or had a clinically significant allergy to drugs, foods, amide local anaesthetics or other materials including commercial artificial tears (in the opinion of the investigator)
  9. 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:

    1. are currently pregnant or,
    2. have a positive result at the urine pregnancy test (Baseline/Day 0) or,
    3. intend to become pregnant during the study treatment period or,
    4. are breast-feeding or,
    5. are 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 Intra Uterine Device (IUD) - during the entire course of and 30 days after the study treatment periods
  10. Any concurrent medical condition, that in the judgment of the PI, might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the patient's well-being
  11. Use of topical cyclosporine, topical corticosteroids or any other topical drug for the treatment of dry eye in either eye within 30 days of study enrolment.
  12. Contact lenses or punctum plug use during the study (previous use not an exclusion criteria but must be discontinued at the screening visit)
  13. History of drug addiction or alcohol abuse
  14. Any prior ocular surgery (including refractive palpebral and cataract surgery) if within 90 days before the screening visit
  15. Participation in a clinical trial with a new active substance during the past 6 months
  16. Participation in another clinical trial study at the same time as the present study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mauro Ferrari, Pharm D +3902583831 info@dompe.it
Contact: Elisa Greco, BSc +3902583831 info@dompe.it
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03982368
Other Study ID Numbers  ICMJE NGF0118
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dompé Farmaceutici S.p.A
Study Sponsor  ICMJE Dompé Farmaceutici S.p.A
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Mauro Ferrari, Pharm D Dompé s.p.a., Milan
PRS Account Dompé Farmaceutici S.p.A
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP