Study to Evaluate Safety and Efficacy of Cenegermin (Oxervate®) vs Vehicle in Severe Sjogren's Dry Eye Disease (NGF0121 - PROTEGO-1 Study)

Dry Eye Clinical Trial

— NGF0121  

Official title:

A 4-week, Phase III, Multicenter, Double-masked, Vehicle-controlled Clinical Study to Evaluate Safety and Efficacy of Oxervate® (Cenegermin) 20 mcg/mL Ophthalmic Solution Versus Vehicle, in Patients With Severe Sjogren's Dry Eye Disease (PROTEGO-1 Study)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05133180
• Other study ID #: NGF0121
• Secondary ID: 2021-003346-21
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 14, 2022
• Est. completion date: July 31, 2023

Study information

• Verified date: June 2023
• Source: Dompé Farmaceutici S.p.A
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study objective is to assess the efficacy and safety of cenegermin (rhNGF) ophthalmic solution at 20 mcg/mL concentration administered three times daily for 4 weeks in patients with severe Sjogren's dry eye disease.

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 will be performed. From the day of screening the patients will stop 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 will be 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 is allowed. During the follow up period, the patient can administer additional artificial tear eye drops, provided by Sponsor, only if strictly needed, and must document in the patient's diary the number of additional drops administered for each eye. Patients will then be followed up for efficacy and safety endpoints until week 16 and for safety endpoints until week 24. The total duration of the study is 25 weeks including 1 week of screening.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 104
• Est. completion date: July 31, 2023
• Est. primary completion date: February 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

12. Use of topical corticosteroids, lifitegrast, autologous serum tears in either eye during the study (previous use not an exclusion criteria but must be discontinued at the screening visit)

13. Contact lenses, True Tear device, moisture goggles, sutureless amniotic membrane or punctum plug use during the study (previous use not an exclusion criteria but must be discontinued at the screening visit)

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.

Related Conditions & MeSH terms

• Dry Eye
• Dry Eye Syndromes
• Eye Diseases
• Keratoconjunctivitis Sicca

Intervention

Drug:
• 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).

Other:
• Vehicle
Vehicle will be instilled with the same scheme of the test product

Locations

Country	Name	City	State
Italy	AOU Gaspare Rodolico - Ospedale San Marco	Catania
Italy	Università degli Studi "Gabriele D'Annunzio" - Ospedale SS. Annunziata - Clinica Oftalmologica	Chieti
Italy	Università degli Studi di Milano - Ospedale San Giuseppe - UO Oculistica	Milan
Italy	AOU Policlinico Umberto I - Dipartimento Organi di Senso - Clinica Oculistica	Roma
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	Lugene Eye Institute - Glendale Office	Glendale	California
United States	Houston Eye Associates HEA - Gramercy Location	Houston	Tennessee
United States	Toyos Clinic - Nashville	Nashville	Tennessee
United States	David Wirta, M.D. & Associates	Newport Beach	California
United States	Virginia Eye Consultants (VEC) - Norfolk Office	Norfolk	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Dompé Farmaceutici S.p.A

Countries where clinical trial is conducted

United States,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Schirmer I test (without anesthesia) >10mm/5min	in the eligible eye	at week 4
Primary	Change from baseline in Symptoms questionnaire (SANDE) global score		at week 12
Secondary	Change from baseline in Schirmer I test (without anesthesia)		At weeks 4, 8, 12 and 16
Secondary	Change from baseline in Cornea and conjunctiva vital staining with fluorescein(National Eye Institute [NEI] scales)		At weeks 4, 8, 12 and 16
Secondary	Change from baseline in Tear Film Break-Up Time (TFBUT)		At weeks 4, 8, 12 and 16
Secondary	Change from baseline in Symptoms questionnaire (SANDE) scores for severity and frequency		At weeks 8, 12 and 16
Secondary	Number of patients experienced a worsening in symptom scores (SANDE) and/or NEI score = 50%		At week 4
Secondary	Quality of life (IDEEL) questionnaire		At weeks 4, 8, 12 and 16