Study to Evaluate Safety and Efficacy of Cenegermin (Oxervate®) vs Vehicle in Severe Sjogren's Dry Eye Disease

NCT05136170 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: NGF02212021-003749-39
• Study Type: interventional
• Target: 85
• Locations: 2 countries
• Sites: 10

Brief Summary

Primary Objectives:

• To compare the efficacy of cenegermin vs vehicle in Schirmer I test (without anaesthesia) \> 10 mm/5 min 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 Disease

Keywords

Sjogren's dry eye

Outcome Measures

Primary Outcomes (2)

• Number of Patients With Schirmer I Test (Without Anesthesia) >10mm/5min in the Eligible Eye at Week 4

  The Schirmer test was used in ophthalmic examination to measure tear production for the diagnosis of conditions such as keratoconjunctivitis sicca and dry eye. Without previously instilling anesthetic drops, the Schirmer strip was 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 was recorded after 5 minutes. 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). Cutoff values: \<5 mm - pathologic dry eye 5-10 mm - marginal dry eye \>10 and \<30 mm - normal secretion The longer, the wetted length, the healthier the status of the eye. No units other than participants were assigned.

  At Week 4 (Visit 3)

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

  SANDE was a short questionnaire to evaluate both dry eye intensity and frequency. It uses a 100 mm horizontal line (Visual Analogue Scale - VAS), for each of the 2 questions, to assess ocular discomfort and/or dryness. Frequency of symptoms ranged from "rarely" (best outcome) to "all of the time" (worst outcome), while the severity of symptoms ranged from "very mild" (best outcome) to "very severe" (worst outcome). Patients had to place a mark on the two given lines based on the extent of their symptoms. The locations of the marks was measured in mm from left to right and recorded as frequency and severity scores, respectively. The SANDE lines for intensity and for severity ranged from 0, being the minimal amount of dry eye symptoms (best outcome) to 100, being the maximal amount of dry eye symptoms (worst outcome). The total SANDE score was calculated by multiplying the frequency score by the severity score and obtaining the square root (0-100; the lower, the better).

  At Week 12 (Visit 5 - Follow up)

Secondary Outcomes (11)

• Key Secondary Outcome: Number of Patients With Schirmer I Test (Without Anesthesia) >10mm/5min at Week 8

  At Week 8 (Visit 4)

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

  At Week 12 (Visit 5 - Follow-up)

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

  At Week 12 (Visit 5 - Follow-up)

• Key Secondary Outcome: Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4.

  At Week 12 (Visit 5 - Follow-up) and Week 4 (Visit 3)

• Key Secondary Outcome: Change From Baseline in Tear Film Break-Up Time (TFBUT) at Week 4, Week 8 and Week 12

  At week 4 (Visit 3) , Week 8 (Visit 4), and Week 12 (Visit 5 - Follow-up)

Other Outcomes (9)

• Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24

  From Screening day (Day -8) up to Week 24 (Visit 7 - Follow-up)

• Use of Preservative Free Artificial Tears Use (Number of Drops/Day).

  Treatment period (Day 1 to Week 4), Follow-up period (Week 4 to Week 24), Overall period (Day 1 to Week 24)

• Change From Baseline in Schirmer I Test (Without Anaesthesia) at Week 2

  At week 2 (Visit 2)

Study Arms (2)

Cenegermin

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: Cenegermin

Vehicle

PLACEBO COMPARATOR

In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days.

Other: Vehicle

Interventions

Cenegermin 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) for 28 consecutive days.

Also known as: Oxervate®

Cenegermin

Vehicle OTHER

Vehicle was instilled with the same scheme of the test product

Also known as: Placebo

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 DED.
• Patients with severe Sjögren's DED 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 ≤ 5 mm/5 min.
• The same eye (eligible eye) must fulfil all the above criteria.
• Patients diagnosed with severe Sjögren's DED at least 3 months before enrolment (current use or recommended use of artificial tears for the treatment of Sjögren's related DE).
• 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.
• Patients who have given written informed consent before any study-related procedures not part of standard medical care are performed.
• Patients must have the ability and willingness to comply with study procedures.
• Patients under treatment with topical cyclosporine (CsA), or topical ophthalmic treatments of the same class for at least 30 days before Screening Visit (Day -8).

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 anaesthetics 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) were excluded from participation in the study if they met any one of the following conditions:
• were currently pregnant or,
• had a positive result at the urine pregnancy test (Baseline/Day 1) or,
• intended to become pregnant during the study treatment period or,
• were breast-feeding or,
• were not willing to use highly effective birth control measures, such as: combined (oestrogen and progesterone containing) hormonal contraceptives associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, implantable, injectable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, sexual abstinence - during the entire course of and 30 days after the study treatment period.
• 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.

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead

Study Sites (10)

Lugene Eye Institute - Glendale Office

Glendale, California, 91204, 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, Massachusetts, 02111, United States

Location

OCLI (Ophthalmic Consultants of Long Island)

Garden City, New York, 11530, United States

Location

Scheie Eye Institute

Philadelphia, Pennsylvania, 19104, United States

Location

Houston Eye Associates HEA - Gramercy Location

Houston, Tennessee, 77025, United States

Location

Toyos Clinic - Nashville

Nashville, Tennessee, 37215, 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 S.p.A.

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This was a double-blind study.The vials containing cenegermin (20 mcg/mL) or vehicle were identical in appearance, and the contents of the vials were indistinguishable. All staff directly involved in the analysis of study results remained masked to treatment assignments while the study was in progress. The blind was not broken for any patient during the study before the database lock.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: multicenter, double-masked, vehicle-controlled study

Study Record Dates

• First Submitted: November 15, 2021
• First Posted: November 29, 2021
• Study Start: January 27, 2022
• Primary Completion: May 24, 2023
• Study Completion: May 24, 2023
• Last Updated: November 26, 2025
• Results First Posted: December 4, 2024

Record last verified: 2025-11

Locations

US (7); IT (3)