Assessment of the Safety and Efficacy of 0.1% RGN-259 Ophthalmic Solution for the Treatment of NK: SEER-2

Neurotrophic Keratopathy Clinical Trial

Official title:

A Phase 3, Multi-Center, Randomized, Parallel, Double Masked, Placebo-Controlled Clinical Study to Assess the Safety and Efficacy of 0.1% RGN-259 Ophthalmic Solution for the Treatment of Neurotrophic Keratopathy (SEER-2)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05555589
• Other study ID #: RGN-NK-302
• Status: Recruiting
• Phase: Phase 3
• Start date: April 11, 2023
• Est. completion date: November 30, 2024

Study information

• Verified date: June 2023
• Source: ReGenTree, LLC
• Contact: Shinwook Kang
• Phone: 609-734-4328
• Email: swkang[@]regentreellc.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to compare the safety and efficacy of RGN-259 to placebo for the treatment of Neurotrophic Keratopathy (NK)

Description:

Neurotrophic keratopathy (NK) is a degenerative corneal disease that occurs as a result of partial or total impairment of trigeminal innervation. The resulting loss of corneal sensitivity (anesthesia) leads to a reduction in lacrimation and a decline in status, metabolism, and mitosis of corneal epithelial cells.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: November 30, 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

1. Be male or female of any race, at least 18 years of age;

2. Have provided written informed consent;

3. Be able and willing to follow instructions, including participation in all study assessments and visits;

4. At the time of Visit 1, have documentation or observation of a Persistent Epithelial Defect (PED) in one or both eyes, defined as a corneal epithelial defect that has not resolved after 1 week of conventional treatment using non-preserved ocular lubricants, non-preserved topical ophthalmic antibiotics, oral doxycycline, patching, amniotic membrane, serum tears, and/or therapeutic contact lenses;

5. Have stage 2 or 3 neurotrophic keratopathy (Mackie Classification) in at least one eye of which the longest dimension (length or width) of the defect measures a minimum length of 1 mm (study eye) and which is confirmed by the Investigator not to be simply superficial punctate keratitis, at Visit 1;

6. Have evidence of decreased corneal sensitivity =40 mm using the Cochet-Bonnet aesthesiometer at Visit 1;

7. Have BCVA score =75 letter counts in the study eye based on the ETDRS protocol;

8. Have at least one eye (the same eye) satisfy all criteria for d, e, f, g above;

9. Female subjects of child-bearing potential must be non-lactating and using and agree to continue using an acceptable method of contraception for at least 4 weeks prior to the first dose of study product and until 12 weeks after last dose, and have a negative urine pregnancy test during screening;

10. Male subjects must agree to use an adequate method of contraception. Exclusion Criteria

1. Have any condition that, in the opinion of the Investigator, would interfere with the subject's ability to complete the study, would interfere with the interpretation of safety or efficacy, or would present an undue risk to the subject.

2. Have any clinically significant slit-lamp findings in the study eye that in the opinion of the Investigator may interfere with the study parameters;

3. Clinically significant active blepharitis, meibomian gland dysfunction (MGD), or lid margin inflammation, or active ocular allergy in study eye that requires treatment that in the opinion of the investigator may interfere with the study parameters;

4. Have a Unanesthetized Schirmer's test score of =3 mm at Visit 1;

5. Have a lid function abnormality (ex. Lagophthalmos) which, in the opinion of the Investigator, is the primary cause of the persistent epithelial defect;

6. Have an ongoing ocular infection (bacterial, viral or fungal) or active inflammation (e.g., follicular conjunctivitis) in the study eye.

7. History of any ocular surgery (including laser or refractive surgical procedures) within the three months before study enrollment.

8. Prior surgical procedure(s) for the treatment of NK (e.g., tarsorrhaphy, conjunctival flap, etc.) within the three months before study enrollment with the exception of amniotic membrane transplantation.

9. Have any planned ocular surgical procedures or are likely to require ocular surgery for the study eye during the study;

10. Have received Botox® injection to induce blepharoptosis in the study eye within 90 days prior to Visit 1;

11. Have used contact lenses (for therapeutic or refractive correction) in the study eye within 14 days prior to Visit 1, or anticipate use of contact lenses during the study period.

12. Have used OxervateTM in the study eye within the past 2 months;

13. Anticipate use of serum tears in the study eye during the study period.

14. Have a presence or history of any ocular or systemic disorder or condition that might hinder the efficacy of the study treatment or its evaluation, could possibly interfere with the interpretation of study results, or could be judged by the Investigator to be incompatible with the study visit schedule or conduct;

15. Have used drugs which affect lacrimation or function of the trigeminal nerve within 30 days of Visit 1 or anticipate use of these systemic medication throughout the course of the study;

16. Have any autoimmune or chronic inflammatory disease that might have hindered the efficacy of the study treatment or its evaluation;

17. Be on topical (Ocular/Nasal) immunosuppressive therapy within 30 days prior to screening or is likely to require this during the course of the study;

18. Have a known allergy and/or sensitivity to the study product or its components;

19. History of drug, medication or alcohol abuse or addiction;

20. Have participated in an investigational drug study within 30 days prior to screening;

21. Have fever, inflammation, or systemic signs of illness suggestive of systemic or invasive infection, including COVID-19 or a positive test for COVID-19, within 2 weeks prior to first dose of study drug.

Related Conditions & MeSH terms

• Neurotrophic Keratopathy

Intervention

Drug:
• RGN-259
A preservative-free, sterile eye drop solution containing Tß4 for direct instillation into study eye(s), five times per day for 28 days
• Placebo
It is composed of the same excipients as RGN-259 but does not contain Tß4. Direct instillation into study eye(s), five times per day for 28 days

Locations

Country	Name	City	State
United States	Tufts Medical Center, Department of Ophthalmology	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Midwest Cornea Associates, LLC.	Carmel	Indiana
United States	Northwestern	Chicago	Illinois
United States	Cleveland Clinic, Cole Eye Institute	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Retina Consultants of Southern Colorado	Colorado Springs	Colorado
United States	University of Miami	Coral Gables	Florida
United States	Cornea Associates of Texas	Dallas	Texas
United States	Connecticut Eye Consultants, P.C. Danbury Eye Physicians & Surgeons	Danbury	Connecticut
United States	Duke Eye Center	Durham	North Carolina
United States	Atlantic Eye	Eatontown	New Jersey
United States	Pacific ClearVision Institute	Eugene	Oregon
United States	Chicago Cornea Consultants	Hoffman Estates	Illinois
United States	Houston Eye Associates	Houston	Texas
United States	Harvard Eye Associates	Laguna Hills	California
United States	Huffman & Huffman, PSC	Lexington	Kentucky
United States	Loma Linda University Eye Institute	Loma Linda	California
United States	Advance Vision Research Institute	Longmont	Colorado
United States	Nvision Clinical Research, LLC.	Los Angeles	California
United States	Vanderbilt Eye Institute	Nashville	Tennessee
United States	Dr. Shultz and Dr. Chan	Northridge	California
United States	Metropolitan Eye Research and Surgery Institute	Palisades Park	New Jersey
United States	UPMC Eye Center	Pittsburgh	Pennsylvania
United States	OHSU Casey Eye Institute	Portland	Oregon
United States	Oculus Research	Raleigh	North Carolina
United States	Black Hills Regional Eye Institute	Rapid City	South Dakota
United States	Washington University Eye Center	Saint Louis	Missouri
United States	MCOA Eye Care	San Antonio	Texas
United States	Thomas Eye Group, P.C.	Sandy Springs	Georgia
United States	University of Washington, Department of Ophthalmology	Seattle	Washington
United States	CORE, Inc. / Vita Eye Clinic	Shelby	North Carolina
United States	University of South Florida, Ophthalmolgoy	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
ReGenTree, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Frequency and severity of AEs	Frequency and severity of AEs as reported according to the NCI CTCAE version 5.0	Day 8, 15, 22, 29, 36, and 43
Other	Number of participants with abnormal vital signs	Blood pressure, heart rate, respiratory rate, oxygen saturation, and body temperature will be measured and assessed its clinical abnormality.	Day 1, 8, 15, 22, 29, 36, and 43
Other	Intraocular Pressure (Unit: mmHg)		Day 1, 8, 29 and 43
Other	Dilated fundoscopy (Vitreous, Retina, Macula, Choroid, Optic Nerve)	The fundoscopy exam will be performed and clinical abnormality of vitreous, retina, Macula, Choroid and Optic Nerve will be described.	Day 1, 8, 29 and 43
Other	Slit-lamp biomicroscopy (Cornea, Conjunctiva, Anterior Chamber, Iris, Lens, Lid)	The Slit-Lamp biomicroscopy will be performed and clinical abnormality of Cornea, Conjunctiva, Anterior Chamber, Iris, Lens and Lid will be described.	Day 1, 8, 15, 22, 29, 36, and 43
Primary	Percentage of subjects achieving complete healing of PED at Day 29	Percentage of subjects achieving complete healing of the Persistent Epithelial Defect (PED) at Day 29 determined by corneal fluorescein staining as measured by the Central Reading Center.	Day 29
Secondary	Percentage of subjects achieving complete healing of PED at Day 29	Percentage of subjects achieving complete healing of the PED determined by corneal fluorescein staining as measured by the Investigator.	Day 29
Secondary	Percentage change from baseline of lesion size	Percentage change from baseline of lesion size determined by corneal fluorescein staining (measurements of greatest dimension of fluorescein staining)	Day 8, 15, 22, 29, 36, and 43
Secondary	NK stage by Mackie classification	NK stage graded according to the Mackie classification (Stage I, II, III. Higher scores mean a better or worse outcome)	Day 8, 15, 22, 29, 36, and 43
Secondary	Visual Acuity determined by ETDRS	Visual Acuity determined by Early Treatment of Diabetic Retinopathy Study (ETDRS)	Day 8, 15, 22, 29, 36, and 43
Secondary	Corneal sensitivity inside the lesion determined by Cochet Bonnet aesthesiometer (Unit: mm)		Day 8, 15, 22, 29, 36, and 43