SEER-3: 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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Regentree LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

29 Aug 2023 → 4 Feb 2025

Decision date (initial)

2023-10-17

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

ReGenTree LLC

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To compare the safety and efficacy of RGN-259 to placebo for the treatment of Neurotrophic Keratopathy (NK)

Secondary objectives 1

1. no secondary objective

Conditions and MedDRA coding

Neurotrophic Keratopathy

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Be male or female of any race, at least 18 years of age at Visit 1
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. Note that re-screened subjects who failed conventional treatment needs to go through 1 week of conventional treatment again right before Visit 1
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 (average of 3 measurements) within the area of the PED or corneal ulceration and outside of the area of the defect within 3 mm of the central cornea 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 4, 5, 6, 7 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 21

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. In cases of uncertainty, the Investigator should contact the medical monitor for clarification
2. Have any clinically significant slit-lamp findings in the study eye at Visit 1 that in the opinion of the Investigator may interfere with the study parameters; Examples include stromal keratitis, numerous punctate keratitis or pterygium, and thin cornea
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. Note that subjects with active stromal herpetic keratitis will also be excluded
7. History of any ocular surgery (including laser or refractive surgical procedures) within the three months before study enrollment. Ocular procedures that are the cause of NK that occurred within 3 months prior to Visit 1 are not exclusionary
8. Prior surgical procedure(s) for the treatment of NK (e.g. tarsorraphy, conjunctival flap, etc) within the three months before study enrollment with the exception of amniotic membrane transplantation. Subjects previously treated with amniotic membrane transplantation may only be enrolled after the membrane has disappeared within the area of the PED or at least four weeks after the date of the amniotic membrane transplantation procedure
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. Note that consented subjects will be instructed to discontinue use of contact lenses for the study eye throughout the study
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. Note that use of preservative free artificial tears for at least two weeks at the time of screening may continue throughout the study at the discretion of the Investigator
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 (eg, progressive or degenerative corneal or retinal conditions, optic neuritis, systemic infection, neoplastic diseases, poorly controlled diabetes)
15. Have used drugs which affect lacrimation or function of the trigeminal nerve (e.g., neuroleptics, antipsychotics and anti-histamine drugs including oral pilocarpine and cevimeline, cholinergics including nasal varenicline, cytotoxic cancer therapy, neuroleptics, and antipsychotics) 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, could possibly have interfered with the interpretation of study results, or could have been judged by the Investigator to be incompatible with the study visit schedule or conduct (e.g., psoriasis, systemic lupus erythematosus, giant cell arteritis, polyarteritis nodosa, relapsing polychondritis, scleroderma, Behcet’s disease, reactive arthritis, inflammatory bowel disease, ankylosing spondylitis, Graves' disease)
17. q. 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; Note that only Systemic and dermal immunosuppressive therapy (including inhalation) with a stable dose for at least two weeks at the time of Visit 1 is permitted
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. In addition, it is necessary that at least 5 half-lives of the previously administered investigational drug have elapsed by Visit 1. Observational studies are not exclusionary
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Percentage of subjects achieving complete healing (defined as 0 mm lesion size) of the Persistent Epithelial Defect (PED) at Visit 5 (Day 29) determined by corneal fluorescein staining as measured by the Central Reading Center. The size of the lesion is based on the longest dimension (length or width) of the defect
2. Safety as determined by the frequency and severity of AEs as reported according to the NCI CTCAE version 5.0, changes from baseline in vital signs, changes in intraocular pressure (IOP), and results of the dilated fundoscopy and slit-lamp exams for both eyes

Secondary endpoints 12

1. Percentage of subjects achieving complete healing (defined as 0 mm lesion size) of the PED determined by corneal fluorescein staining as measured by the Central Reading Center at Visits 2, 3, 4, 6, and 7
2. Percentage of subjects achieving complete healing (defined as <0.5 mm lesion size) of the PED determined by corneal fluorescein staining as measured by the Investigator at Visits 2-7
3. Time to complete healing of the PED as measured by the Central Reading Center
4. Time to complete healing of the PED as measured by the Investigator
5. Percentage change from baseline of lesion size determined by corneal fluorescein staining as measured by the Central Reading Center at Visit 2-7 (measurements of greatest dimension of fluorescein staining)
6. Percentage change from baseline of lesion size determined by corneal fluorescein staining as measured by the Investigator at Visit 2-7 (measurements of greatest dimension of fluorescein staining)
7. NK stage (Mackie Classification) determined by corneal fluorescein staining as measured by the Investigator at Visits 2-7
8. Visual Acuity determined by Early Treatment of Diabetic Retinopathy Study (ETDRS) at Visits 2-7
9. Corneal sensitivity inside the lesion determined by Cochet Bonnet aesthesiometer at Visits 2-7
10. Change from baseline in Ocular discomfort, Photophobia, Foreign body sensation, Burning and Dryness using VAS at Visit 3 and Visit 5
11. Proportion of subjects achieving complete healing (defined as 0 mm lesion size) of the PED determined by corneal fluorescein staining as measured by the Central Reading Center over multiple visits from visit 2 to visit 5
12. Proportion of subjects achieving complete healing (defined as <0.5 mm lesion size) of the PED determined by corneal fluorescein staining as measured by the Investigator over multiple visits from visit 2 to visit 5

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Regentree LLC

Sponsor organisation

Regentree LLC

Address

116 Village Boulevard Suite 200

City

Princeton

Postcode

08540-5700

Country

United States

Scientific contact point

Organisation

Regentree LLC

Contact name

Jihye Sung

Public contact point

Organisation

Regentree LLC

Contact name

Jihye Sung

Third parties 5

Sponsor responsibilities

Article 77 compliance

Regentree LLC

Article 77 implementation

Regentree LLC

Locations

4 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 88 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications