Safety and Efficacy Study on Cenegermin (Oxervate®) vs Vehicle in Severe Sjogren's Dry Eye Disease (PROTEGO-1 Study)

NCT05133180 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: NGF01212021-003346-21
• Study Type: interventional
• Target: 104
• Locations: 2 countries
• Sites: 10

Brief Summary

Primary objectives

• To compare the efficacy of cenegermin vs vehicle in Schirmer I test (without anaesthesia) \>10mm/5min at Week 4 by testing the superiority.
• To compare the efficacy of cenegermin vs vehicle in Symptom Assessment in Dry Eye questionnaire (SANDE) global score at Week 12 by testing the superiority. Secondary objectives
• To compare the efficacy of cenegermin vs vehicle in Schirmer I test at Week 4, 8, 12 and 16 by testing the superiority.
• To compare the efficacy of cenegermin vs vehicle in Cornea and conjunctiva vital staining with fluorescein (National Eye Institute \[NEI\] scales) at Week 4, 8, 12 and 16 by testing the superiority.
• To compare the efficacy of cenegermin vs vehicle in Tear Film Break-Up Time (TFBUT) at Week 4, 8, 12 and 16 by testing the superiority.
• To compare the efficacy of cenegermin vs vehicle in SANDE scores at Week 8, 12 and 16 by testing the superiority.
• To compare the efficacy of cenegermin vs vehicle in worsening in symptom scores (SANDE) and/or NEI score at Week 4 by testing the superiority.
• To compare the efficacy of cenegermin vs vehicle in impact of dry eye on everyday life (IDEEL) questionnaire at Week 4, 8, 12 and 16 by testing the superiority.

Conditions

Dry Eye

Keywords

Sjorgen's dry eye

Outcome Measures

Primary Outcomes (2)

• Number of Patients Reaching a Value of Schirmer I Test (Without Anaesthesia) >10mm/5min at Week 4

  The Schirmer test type I (without anaesthesia) was performed to measure aqueous tear secretion. The rounded bend end of a sterile strip was inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes had elapsed, the Schirmer's test strip was removed and the length of the tear absorption on the strip was measured (millimeters/5 minutes). The longer the wetted length, the healthier the status of the eye.

  at week 4

• Change From Baseline in Symptoms Questionnaire (SANDE) Global Score at Week 12

  The SANDE questionnaire is comprised of two questions: 1) How often do your eyes feel dry and/or irritated? And 2) How severe you feel your symptoms of dryness and/or irritation are? The SANDE questionnaire uses a 100 mm horizontal line for each question to assess the extent of patients' symptoms. In this questionnaire, frequency of symptoms ranges from "rarely" (0) to "all of the time" (100) and the severity of symptoms ranges from "very mild" (0) to "very severe" (100). At each visit, patients were asked to place a mark on the two given lines based on the extent of their symptoms. The locations of the marks made by the patients on the 100 mm horizontal lines were measured in mm from left to right. The global SANDE score is calculated by multiplying the frequency score by the severity score and obtaining the square root. Both for total score and for frequency or severity scores, 0 is the best condition, 100 the worst condition. Please note that adjusted means are reported.

  at week 12

Secondary Outcomes (18)

• Key Secondary Outcome: Number of Patients Reaching a Value of Schirmer I Test (Without Anaesthesia) > 10mm/5min at Week 8

  at Week 8

• Key Secondary Outcome: Change From Baseline in Symptoms Assessment in Dry Eye (SANDE) Score for Frequency at Week 12

  At week 12

• Key Secondary Outcome: Change From Baseline in Symptoms Assessment in Dry Eye (SANDE) Score for Severity at Week 12

  at Week 12

• Key Secondary Outcome: Change From Baseline in Quality of Life Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4

  At Weeks 12 and 4

• Key Secondary Outcome: Change From Baseline in "Treatment Satisfaction & Bother" Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Weeks 12 and 4

  at Weeks 12 and 4

Other Outcomes (1)

• Incidence and Frequency of TEAEs, Assessed Throughout the Study.

  From Screening to Visit 7 (follow-up, week 24)

Study Arms (2)

Oxervate

EXPERIMENTAL

One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours.

Drug: Oxervate

Vehicle

PLACEBO COMPARATOR

One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours).

Other: Vehicle

Interventions

Oxervate DRUG

Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).

Also known as: Cenegermin

Oxervate

Vehicle OTHER

Vehicle will be instilled with the same scheme of the test product

Also known as: Reference product

Vehicle

Eligibility Criteria

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

You may qualify if:

• Male or female aged ≥ 18 years
• Patients with a confirmed diagnosis of Sjögren's syndrome or other autoimmune disease known to induce Sjögren's Dry Eye Disease (DED).
• Patients with severe Sjögren's dry eye disease characterized by the following clinical features:
• Corneal and/or conjunctival staining with fluorescein using National Eye Institute (NEI) grading system ≥3
• SANDE questionnaire \>25 mm
• Schirmer test I (without anaesthesia) ≥2 ≤5mm/5min
• The same eye (eligible eye) must fulfill all the above criteria
• Patients diagnosed with severe Sjögren's dry eye disease at least 3 months before enrolment
• Best corrected distance visual acuity (BCDVA) score of ≥ 0.1 decimal units (20/200 Snellen value) in each eye at the time of study enrolment
• If a female of childbearing potential, have a negative urine pregnancy test and use a highly effective method to avoid pregnancy for the duration of the trial and 30 days after the study treatment period. Males of reproductive potential should use effective contraception during treatment and 30 days after the study treatment period.
• 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 IRB/IEC for the current study
• Patients must have the ability and willingness to comply with study procedures.

You may not qualify if:

• 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
• Evidence of an active ocular infection, in either eye
• Presence of any other ocular disorder or condition requiring topical medication during the entire duration of study in either eye
• History of severe systemic allergy or of ocular allergy (including seasonal conjunctivitis) or chronic conjunctivitis and/or keratitis other than dry eye
• Intraocular inflammation defined as Tyndall score \>0
• History of malignancy in the last 5 years
• 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
• 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 anesthetics or other materials including commercial artificial tears (in the opinion of the investigator).
• 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 at the urine pregnancy test (Baseline/Day 1) or,
• intend to become pregnant during the study treatment period or,
• are breast-feeding or,
• are not willing to use highly effective birth control measures
• During the entire course of and 30 days after the study treatment periods

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead

Study Sites (10)

Lugene Eye Institute - Glendale Office

Glendale, California, 91204, United States

Location

David Wirta, M.D. & Associates

Newport Beach, California, 92663, United States

Location

The Johns Hopkins University

Baltimore, Maryland, 21218, United States

Location

Tufts University School of Medicine (TUSM) - New England Eye Center/Tufts Medical Center - Boston

Boston, Massachusetts, 02111, United States

Location

Houston Eye Associates HEA - Gramercy Location

Houston, Tennessee, 77025, United States

Location

Toyos Clinic - Nashville

Nashville, Tennessee, 37215, United States

Location

Virginia Eye Consultants (VEC) - Norfolk Office

Norfolk, Virginia, 23502, United States

Location

AOU Gaspare Rodolico - Ospedale San Marco

Catania, 95123, Italy

Location

Università degli Studi di Milano - Ospedale San Giuseppe - UO Oculistica

Milan, 20123, Italy

Location

AOU Policlinico Umberto I - Dipartimento Organi di Senso - Clinica Oculistica

Roma, 00161, Italy

Location

MeSH Terms

Conditions

Dry Eye Syndromes

Interventions

cenegermin

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases

Results Point of Contact

• Title: Clinical Development & Operations
• Organization: Dompé farmaceutici SpA

clinical.trials@dompe.com

+39 02 583831

Study Officials

• Flavio Mantelli, MD

  Dompé Farmaceutici

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: double-masked study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2021
• First Posted: November 24, 2021
• Study Start: January 19, 2022
• Primary Completion: September 22, 2022
• Study Completion: December 19, 2022
• Last Updated: June 7, 2024
• Results First Posted: June 7, 2024

Record last verified: 2024-05

Locations

US (7); IT (3)