PHase 3, Multicenter, RandOmized, Double-masked, PlacEbo-CoNtrolled Study of TInlarebant to EXplore Safety and Efficacy in the Treatment of Geographic Atrophy (the PHOENIX Study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Belite Bio Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

28 Mar 2024 → ongoing

Decision date (initial)

2024-02-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Belite Bio Inc.

External identifiers

EU CT number

2023-503931-17-00

WHO UTN

U1111-1297-0157

ClinicalTrials.gov

NCT05949593

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To measure the rate of change (growth rate slope) in geographic atrophy (GA) lesion size as determined by fundus autofluorescence (FAF) photography from baseline to Month 24

Secondary objectives 1

1. To measure the change in best-corrected visual acuity (BCVA) as assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale under standard luminance and low luminance from baseline to Month 24

Conditions and MedDRA coding

Geographic Atrophy

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Subjects must be willing and able to provide signed informed consent prior to participation in any study-related procedures.
2. 2. Males or females, 60 to 85 years of age.
3. 3. Subjects must have a confirmed diagnosis of GA with atrophic lesions (diagnosed as GA) in 1 or both eyes, measuring 0.5 to 10 mm2 in aggregate area as assessed by FAF photography and determined by a central reading center. - For lesions with foveal involvement, BCVA in the study eye should be 20/80 or better (≥ 54 ETDRS letters) - For lesions without any foveal involvement, BCVA in the study eye should be 20/100 or better (≥ 49 ETDRS letters) - No minimum BCVA is required in the fellow eye
4. 4. Ability to adequately examine the study eye fundus at enrollment (the subject must have sufficiently clear ocular media, adequate pupillary dilation, fixation to permit quality fundus imaging, and the ability to cooperate sufficiently for adequate ophthalmic visual function testing).
5. 5. Female subjects must be nonpregnant and nonlactating. Male subjects whose partners are fertile, and women of childbearing potential (WOCBP) must use only highly effective contraception methods for the entire study duration and not donate sperm or eggs throughout the entire study from the date of informed consent until 89 days (WOCBP) or 149 days (men) after the last dose of the study treatment in case of early treatment termination.

Exclusion criteria 31

1. 1. Any GA lesions larger than 10 mm2 in the study eye.
2. 10. Myopia > -8 D in the study eye.
3. 11. Hypermetropia > +8 D in the study eye.
4. 12. Current use and unwillingness to discontinue oral prescription-strength retinoid-based products. Subjects who discontinue oral use of the prescription-strength retinoid-based products for a period of at least 30 days prior to Screening may be considered for enrollment. Ocular topical medications containing retinoids and vitamin A-based drugs or medications should be stopped at least 30 days prior to Screening.
5. 13. Use of systemic medications and nonprescription supplements containing vitamin A or vitamin A derivatives during the study. Use of these medications or supplements must be stopped at least 30 days prior to Screening, or within the washout period of the medication, whichever is longer. Multivitamin supplements not containing vitamin A or vitamin A derivatives are allowed. The use of topical medications (except topical ophthalmological medications) containing vitamin A or vitamin A derivatives is allowed. Topical ophthalmic medications that do not contain vitamin A or vitamin A derivatives are allowed.
6. 2. The presence of diabetic macular edema or macular disease in either eye.
7. 3. Diabetic retinopathy more advanced than mild nonproliferative diabetic retinopathy, or any other retinal vascular disease in either eye.
8. 4. Plans to undergo inpatient surgical procedures during the study.
9. 5. Incisional ocular surgery in the study eye 3 months prior to screening and/or plans to undergo intraocular surgery (including cataract surgery) in the study eye during the study. a) Cataract surgery is allowed when done more than 8 weeks prior to Screening. b) YAG capsulotomy and laser iridotomy are allowed when done more than 4 weeks prior to Screening. c) Any postoperative treatment regimen following the above interventions needs to be terminated more than 4 weeks prior to Screening.
10. 6. Presence or history of choroidal neovascularization (CNV) in the study eye as determined by optical coherence tomography angiography (OCT-A) and confirmed by a central reading center. If OCT-A results are inconclusive to confirm the presence/absence of CNV, as determined by central imaging center, fluorescein angiography may be performed at the discretion of the Study Investigator. Upon Sponsor’s approval in advanced, fluorescein angiography could be performed and assessed by the Study Investigator and designee, to replace OCT-A if site does not have feasible device.
11. 7. Inflammatory disease of the retina, uvea, or choroid in either eye within 1 year of study enrollment.
12. 8. Any form of uncontrolled glaucoma in the study eye based on the criteria below assessed at Screening: - Intraocular pressure > 25 mm Hg - Glaucomatous visual field, or disc cupping considered clinically significant (CS) for advanced glaucoma (cup to-disc ratio > 0.6).
13. 9. Severe dry eye disease.
14. 14. Any prior or current use of retinotoxic drugs.
15. 15. Investigational drug use of any kind in the previous 3 months.
16. 16. Any prior ocular gene therapy.
17. 17. Any prior intraocular, periocular, or intravitreal injection of any drug in the either eye in the previous 3 months.
18. 18. Prior macular laser photocoagulation treatment or any history of photodynamic therapy in the study eye. Prior extramacular laser photocoagulation treatment is allowed, but not within 1 year prior to enrollment in the study.
19. 19. Use of any known drugs or supplements that are inhibitors/inducers of cytochrome P450 enzymes (e.g., Clarithromycin, Fluvoxamine, Ketoconazole, Rifampin, Carbamazepine, St. John’s wort) starting within 30 days of first study treatment administration, or regular consumption of foods that are inhibitors/inducers of cytochrome P450 enzymes (e.g., grapefruit, pomegranate, star fruit, bitter orange [Seville orange]) starting within 48 hours of first study treatment administration that, in the investigator’s judgment, may impact subject safety or the validity of the study results.
20. 20. Use of Pentosan Polysulfate Sodium (e.g. ELMIRON®) 30 days prior to the first study treatment dose and during the study.
21. 21. Use of breast cancer resistance protein inhibitors that cannot be stopped within 30 days prior to the first study treatment dose and during the study (e.g., Cyclosporine A, Darolutamide, Fostamatinib).
22. 22. Presence of life-threatening disease(s), including malignancies requiring current treatment.
23. 23. Abnormal cardiac rhythm not controlled with medication or history of stroke, coronary events, and/or heart failure within 1 year prior to enrollment.
24. 24. Uncontrolled hypertension as defined by blood pressure ≥ 160 systolic or ≥ 100 diastolic (note: investigator to take the better of at least 2 measurements).
25. 25. Alanine aminotransferase/aspartate aminotransferase > 2.5 × the upper limit of normal.
26. 26. Previous diagnosis of Moderate, Severe, or End Stage kidney disease (Stages 3B – 5), estimated Glomerular filtration rate (eGFR) of 44 mL/min/1.73m2 or less), or current use of medications to manage cardiovascular risk associated with chronic kidney disease.
27. 27. Body mass index ≥ 40.
28. 28. Hemoglobin A1c ≥ 8%.
29. 29. Unwillingness or inability to provide signed informed consent prior to participation in any study-related procedures.
30. 30. Pregnant or nursing female subjects; women of childbearing potential who are unwilling or unable to use an acceptable method of contraception (or abstinence). Women of childbearing age must have a negative pregnancy test prior to randomisation.
31. 31. Male subjects who are unwilling or unable to use an acceptable method of contraception (or abstinence) and who do not agree that female spouses/partners will use adequate contraception or be of nonchildbearing potential (i.e., surgically sterile).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint of this study is the annualized rate of change in atrophic lesion size (growth rate slope in mm2/year) using all available timepoint measurements over the 24-month study period. Both untransformed and transformed (square root) analyses of lesion growth will be performed.

Secondary endpoints 16

1. • Change in BCVA as assessed by ETDRS letter score under standard luminance and low luminance from baseline to Month 24
2. • Exploratory endpoint: Change in photoreceptor morphology (EZ defect area) from baseline to Month 24 (assessed by SD-OCT at the horizontal meridian passing through the foveal center)
3. • Exploratory endpoint: Change in outer, middle, and central subfield retinal thickness from baseline to Month 24 (assessed by SD OCT)
4. Other secondary endpoints: • Change in morphology/anatomy of the RPE and outer retina atrophy from baseline to Month 24
5. Other secondary endpoints: • Annualized rate of change in atrophic lesion size (growth rate slope) as determined by CFP from baseline to Month 24. Both untransformed and transformed (square root) analyses of lesion growth will be performed.
6. • Correlation between reduction of plasma RBP4 and change in aggregate atrophic lesion size from baseline to Month 24
7. • Change in retinal sensitivity as assessed by microperimetry from baseline to Month 24
8. Safety endpoint: • Adverse events (AEs), as defined by the incidence of treatment emergent AEs (TEAEs), serious AEs, drug-related TEAEs, and drug-related serious Aes
9. Safety endpoint: • Laboratory parameters (hematology, serum chemistry, urinalysis, retinol chemistries)
10. Safety endpoint: • Vital signs
11. Safety endpoint: • Electrocardiograms (ECGs)
12. Safety endpoint: • Ophthalmological examinations
13. Safety endpoint: • Color fundus photography (CFP)
14. Safety endpoint: • Change in patient-reported outcome measures using the NEI VFQ-25 and LLQ from baseline to Month 24
15. Safety endpoint: • Contrast Sensitivity
16. Safety endpoint: • Dark Adaptation Test (to be completed at selected sites)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Belite Bio Inc.

Sponsor organisation

Belite Bio Inc.

Address

Ugland House, P. O. Box 309 P. O. Box 309

City

Grand Cayman

Postcode

KY1-1104

Country

Cayman Islands

Scientific contact point

Organisation

Belite Bio Inc.

Contact name

Chief Scientific Officer

Public contact point

Organisation

Belite Bio Inc.

Contact name

Clinical Project Manager

Third parties 9

Locations

2 EU/EEA countries · 7 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

Documents 25 files

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

Application history

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