Phase 3 Multicenter Randomized Double-Masked Placebo-Controlled Trial of Tinlarebant in Geographic Atrophy Treatment
- Trial ID
- 2023-503931-17-00
- Protocol
- LBS-008-CT05
- Sponsor
- Belite Bio Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 3, multicenter, randomized, double-masked, placebo-controlled study is to evaluate the **rate of change** in geographic atrophy (GA) lesion size. This is determined by fundus autofluorescence (FAF) photography from baseline to Month 24. Understanding the growth rate of GA lesions is clinically significant as it can provide insights into the progression of the disease and the potential efficacy of the investigational drug, Tinlarebant, in slowing this progression.
Secondary objectives include measuring the change in best-corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale under standard luminance and low luminance from baseline to Month 24. This assessment is crucial for evaluating the functional impact of the treatment on visual performance, which is a key concern for patients with geographic atrophy.
Participants
The clinical trial involves a total of **364 participants** diagnosed with **Geographic Atrophy**. The study population comprises both male and female subjects aged between 60 to 85 years. Participants were selected based on their confirmed diagnosis of geographic atrophy with atrophic lesions in one or both eyes, as determined by fundus autofluorescence photography. The trial does not include a vulnerable population. Participants are required to have sufficiently clear ocular media and adequate pupillary dilation to allow for quality fundus imaging. Lifestyle considerations such as diet and physical activity are not specified. The trial includes individuals who are nonpregnant and nonlactating, with a requirement for highly effective contraception methods for the duration of the study. The selection criteria ensure that participants have the ability to cooperate sufficiently for ophthalmic visual function testing.
Plans and Procedures
The clinical trial is a **Phase 3**, multicenter, randomized, double-masked, placebo-controlled study designed to evaluate the safety and efficacy of **Tinlarebant** in the treatment of **Geographic Atrophy**. The trial aims to measure the rate of change in geographic atrophy lesion size over a 24-month period, utilizing fundus autofluorescence photography. Participants will be randomly assigned to receive either the active drug, Tinlarebant, or a placebo that matches the active drug in size, appearance, and other physical properties. The trial is expected to commence recruitment in February 2024 and conclude by November 2025.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of geographic atrophy, and visual acuity requirements. Following successful screening, participants will be enrolled and randomized into the study. Regular follow-up visits will occur throughout the trial duration to monitor safety and efficacy endpoints, including changes in best-corrected visual acuity (BCVA), photoreceptor morphology, and retinal thickness. Safety assessments will include adverse event monitoring, laboratory tests, vital signs, electrocardiograms, and ophthalmological examinations.
The expected length of participant involvement is 24 months, with study visits scheduled at regular intervals to ensure comprehensive data collection. Conditions that may lead to early termination from the study include the occurrence of serious adverse events or withdrawal of consent by the participant. The end-of-study visit will involve final assessments to evaluate the primary and secondary endpoints, ensuring a thorough analysis of the treatment's impact on geographic atrophy progression.
Treatment
The clinical trial involves the administration of **Tinlarebant** (LBS-008), an investigational medication, in the form of a tablet. The active substance in LBS-008 is Tinlarebant, which is of chemical origin. The tablets are administered orally with a maximum daily dose of 5 mg. The total maximum dose over the treatment period is 3360 mg, with the treatment duration extending up to 24 months. The pharmaceutical form of the medication is a tablet, and it is produced by Belite Bio Inc. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the prescribed regimen.
The study also includes a **placebo** group to match Tinlarebant (LBS-008). The placebo tablets are prepared using microcrystalline cellulose in place of the active drug substance. These placebo tablets are identical in size, appearance, and other physical properties to the LBS-008 tablets, ensuring blinding in the double-masked study design. The placebo is administered orally, following the same dosing schedule as the active medication, to maintain consistency across treatment groups. The use of a placebo allows for the assessment of the efficacy and safety of Tinlarebant by providing a comparator within the study.
Efficacy
The efficacy of the investigational product, **Tinlarebant**, in the treatment of **Geographic Atrophy (GA)** will be assessed through a series of predefined endpoints over a 24-month study period. The primary efficacy endpoint is the annualized rate of change in atrophic lesion size, measured as the growth rate slope in mm²/year. This will be evaluated using all available timepoint measurements, with both untransformed and transformed (square root) analyses of lesion growth being performed.
Secondary endpoints include changes in Best Corrected Visual Acuity (BCVA) as assessed by the ETDRS letter score under standard and low luminance conditions, from baseline to Month 24. Additional exploratory endpoints involve changes in photoreceptor morphology, specifically the EZ defect area, and retinal thickness, assessed by Spectral Domain Optical Coherence Tomography (SD-OCT) at the horizontal meridian passing through the foveal center. Other secondary endpoints include changes in the morphology and anatomy of the Retinal Pigment Epithelium (RPE) and outer retina atrophy, as well as the annualized rate of change in atrophic lesion size determined by Color Fundus Photography (CFP). The correlation between the reduction of plasma Retinol Binding Protein 4 (RBP4) and changes in aggregate atrophic lesion size will also be evaluated.
Retinal sensitivity changes will be assessed using microperimetry, and patient-reported outcomes will be measured using the NEI VFQ-25 and LLQ from baseline to Month 24. These assessments will provide comprehensive data on the efficacy of Tinlarebant in slowing the progression of GA and improving visual function.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Subjects must be willing and able to provide signed informed consent prior to participation in any study-related procedures.
- Males or females, 60 to 85 years of age.
- 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
- 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).
- 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
- Any GA lesions larger than 10 mm2 in the study eye.
- Myopia > -8 D in the study eye.
- Hypermetropia > +8 D in the study eye.
- 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.
- 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.
- The presence of diabetic macular edema or macular disease in either eye.
- Diabetic retinopathy more advanced than mild nonproliferative diabetic retinopathy, or any other retinal vascular disease in either eye.
- Plans to undergo inpatient surgical procedures during the study.
- 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.
- 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.
- Inflammatory disease of the retina, uvea, or choroid in either eye within 1 year of study enrollment.
- 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).
- Severe dry eye disease.
- Any prior or current use of retinotoxic drugs.
- Investigational drug use of any kind in the previous 3 months.
- Any prior ocular gene therapy.
- Any prior intraocular, periocular, or intravitreal injection of any drug in the either eye in the previous 3 months.
- 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.
- 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.
- Use of Pentosan Polysulfate Sodium (e.g. ELMIRON®) 30 days prior to the first study treatment dose and during the study.
- 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).
- Presence of life-threatening disease(s), including malignancies requiring current treatment.
- Abnormal cardiac rhythm not controlled with medication or history of stroke, coronary events, and/or heart failure within 1 year prior to enrollment.
- Uncontrolled hypertension as defined by blood pressure ≥ 160 systolic or ≥ 100 diastolic (note: investigator to take the better of at least 2 measurements).
- Alanine aminotransferase/aspartate aminotransferase > 2.5 × the upper limit of normal.
- 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.
- Body mass index ≥ 40.
- Hemoglobin A1c ≥ 8%.
- Unwillingness or inability to provide signed informed consent prior to participation in any study-related procedures.
- 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.
- 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).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Recruiting | 24 Feb 2024 | 80 |
 France | Recruiting | 24 Feb 2024 | 65 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo to Match Tinlarebant (LBS-008). Placebo tablets will be prepared similarly with microcrystalline cellulose used in place of the active drug substance. The placebo tablet is identical in size, appearance, and other physical properties to the LBS-008 tablet. | Placebo | N/A | — | — | — | N/A |
LBS-008 | Test | TABLET | ORAL | 5 | 24 | PRD10462808 |