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

NCT ID: NCT05133180

Last Updated: 2024-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-19
• Study Completion Date: 2022-12-19

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.

Detailed Description

This is a 4 week phase III, multicenter, double-masked, vehicle-controlled study to evaluate safety and efficacy of cenegermin ophthalmic solution at 20 mcg/mL solution versus vehicle, in patients with severe Sjogren's dry eye disease.

During the screening all procedures for inclusion and exclusion were performed. From the day of screening the patients stopped any kind of further treatment, except commercially available preservative free artificial tears provided by Sponsor.

At the end of the wash out period, patients meeting the entry criteria for this study were randomized 1:1 and treated for 4 weeks with either cenegermin ophthalmic solution 20 mcg/mL TID or vehicle TID.

During the 4 weeks of masked treatment only the administration of IMP was allowed.

During the follow up period, the patient could administer additional artificial tear eye drops, provided by Sponsor, only if strictly needed, and should document in the patient's diary the number of additional drops administered for each eye.

Patients were then followed up for efficacy and safety endpoints until week 16 and for safety endpoints until week 24.

The total duration of the study was 25 weeks including 1 week of screening.

Conditions

Dry Eye

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Oxervate

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.

Group Type: EXPERIMENTAL

Oxervate

Intervention Type: 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).

Vehicle

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

Group Type: PLACEBO_COMPARATOR

Vehicle

Intervention Type: OTHER

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

Interventions

Oxervate

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).

Intervention Type: DRUG

Vehicle

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

Intervention Type: OTHER

Other Intervention Names

Cenegermin; Reference product

Eligibility Criteria

Inclusion Criteria

1. Male or female aged ≥ 18 years

2. Patients with a confirmed diagnosis of Sjögren's syndrome or other autoimmune disease known to induce Sjögren's Dry Eye Disease (DED).

3. Patients with severe Sjögren's dry eye disease 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) ≥2 ≤5mm/5min

4. The same eye (eligible eye) must fulfill all the above criteria

5. Patients diagnosed with severe Sjögren's dry eye disease at least 3 months before enrolment

6. 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

7. 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.

8. 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

9. 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 in either eye

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 anesthetics 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 1) 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

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, or topical ophthalmic treatments of the same class, within 14 days of screening visit (day -8)

14. History of drug addiction or alcohol abuse in the last 2 years

15. Any prior ocular surgery (including refractive, palpebral and cataract surgery) if within 90 days before the screening visit

16. Participation in a clinical trial with a new active substance during the past 3 months

17. Participation in another clinical trial study at the same time as the present study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dompé Farmaceutici S.p.A

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Flavio Mantelli, MD

Role: STUDY_DIRECTOR

Dompé Farmaceutici

Locations

Lugene Eye Institute - Glendale Office

Glendale, California, United States

David Wirta, M.D. & Associates

Newport Beach, California, United States

The Johns Hopkins University

Baltimore, Maryland, United States

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

Boston, Massachusetts, United States

Houston Eye Associates HEA - Gramercy Location

Houston, Tennessee, United States

Toyos Clinic - Nashville

Nashville, Tennessee, United States

Virginia Eye Consultants (VEC) - Norfolk Office

Norfolk, Virginia, United States

AOU Gaspare Rodolico - Ospedale San Marco

Catania, , Italy

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

Milan, , Italy

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

Roma, , Italy

Countries

United States; Italy

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2021-003346-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NGF0121

Identifier Type: -

Identifier Source: org_study_id