IRB Study Number 24-182
Status Recruiting
Phase Phase 3
Location i Building - Cole Eye Institute
Institute Cole Eye Institute
Description
The purpose of this research study is to test and determine how safe and how well bel-sar study treatment works compared to sham (no study drug or laser) in participants who have a type of eye cancer called an indeterminate lesion (a growth in your eye that is suspected to be melanoma) or choroidal melanoma, also known as eye melanoma.. The sham arm will be used to see how safe and how well the active study treatment works compared to no treatment.
Aura Biosciences, Inc. is currently developing an investigational treatment called belzupacap sarotalocan (bel-sar), which is administered into the eye using an investigational device called a microinjector (made by a company called Clearside Biomedical Inc), after which the drug (bel-sar) is activated by an investigational laser system (made by Quantel Medical) for the treatment of choroidal melanoma (CM). Investigational means that this study treatment has not been approved by the United States Food and Drug Administration (FDA) but is available in research studies like this one. A research study tests if a study treatment works and if it is safe to use. Bel-sar is a light activated liquid which aims to target and destroy tumor cells in the eye.
In this study you will be asked to visit the study center around 29 times to have tests and assessments. The following will happen at some point in the study:
- Blood samples will be taken
- Your blood pressure and heart rate will be measured
- Vision exams- your best distance vision with eyeglasses or contact lenses will be checked
- Other eye exams- These include checks of various parts of the eye which will require a combination of lights, numbing drops, dilating drops, cameras, and ultrasounds
- Receive your assigned study treatment (investigational or sham)
Your participation in the research will last about 104 weeks.
Inclusion Criteria
1.Be at least 18 years of age of either sex or any race.
2.Have been informed about the nature and requirements of the trial, voluntarily agreed to participate in the trial and follow all trial procedures and documented their consent by signing the Informed Consent Form before participating in any trial-related activities.
3.Have no evidence of metastatic disease confirmed per the SoC and at a minimum by abdominal and chest imaging within 2 months prior to enrollment.
4.Be treatment naïve for their IL/CM (Note: eligibility for subjects who have received treatment with photodynamic therapy >12 months prior to enrollment should be discussed with the medical monitor for approval prior to enrollment).
5.Have per the Investigator’s expert clinical judgment, a clinical diagnosis of primary IL/CM based on the clinical history, ophthalmic examination, FP and conventional ocular ultrasound for whom observation-only (i.e., a watchful waiting approach) could be an appropriate standard of care.
6.Have the following based on SoC trial site and/or referring site measurements (at a minimum based on B-scan):
a. Increase in tumor thickness of ≥0.25 mm based on intra-site measurements (i.e.,both measurements at trial site) comparing the oldest measurement within 2 years of screening to site-determined screening measurement. At least 1 historical measurement within 2 years of screening is required and it (or the oldest measurement if multiple measurements are available) must be at least 3 months prior to the site-determined screening measurement.
OR
Increase in tumor thickness of ≥0.4 mm based on inter-site measurements (i.e.,between referring site and trial site measurements) comparing the oldest measurement (within 2 years and at least 3 months before of the initial study site evaluation) to the initial study site measurement, However, IF relying on the inter-site measurements for increase of ≥0.4 mm for inclusion, THEN confirmation of growth by the study site investigator is required via one of the following 2methods:
i.PREFERABLE: confirmation of tumor growth at the study site (≥ 0.13mmincrease in tumor thickness compared to the initial study site evaluation) at least 2 months later.
OR
ii. ALLOWABLE (but not preferred): Study site Investigator is able to personally review prior referring site fundus photographs and confirm an increase in tumor basal diameter/extent of tumor edge of at least 0.25 Disc Diameters (DD; equal to 325 microns), with a RATE of ≥0.25 DD per 6 months interval. (For example, if the previous photo is from 6 months prior, then the Investigator must determine that the extension of the tumor border, or the tumor diameter, has increased by ≥0.25 DD. However, if the previous photo was from 12 months prior, then the Investigator must determine that the extension of the tumor border, or the tumor diameter, has increased by ≥0.5 DD. Similarly, if the previous photo was from 21 months prior, then the Investigator must determine that the extension of the tumor border, or the tumor diameter, has increased by ≥0.875 DD. The previous photo could be from less than 6 months prior, however the minimum absolute growth of at least 0.25 DD must have been attained during this time interval.) All previous fundus photos on which this determination relied must be available as source documents. B-scan measurements are not required for this confirmation of increase in tumor basal diameter/extent of tumor edge as it should be based on fundus photographs.
b.Tumor thickness growth rate ≥0.2 mm/year and <1.0 mm/year using simple linear regression based on all site (and/or referring site) measurements of tumor thickness within 2 years of screening and the site-determined screening measurement.
Notes:
•Since these are Investigator assessed criteria (6a and 6b), if at least 1 historical measurement from the trial site in addition to historical measurement(s) from referring site within 2 years of screening are available, these criteria can be assessed solely based on trial site measurements for consistency and/or accuracy per Investigator judgment.
•For de-novo lesions, evidence of no lesion (i.e., 0 mm thickness) based on FP (within2 years of screening and at least 3 months prior to the site-determined screening measurement) is acceptable in lieu of a historical measurement for assessment of this criterion. For assessment of increase in tumor thickness and growth rate calculation in this criterion, the historical value will be considered 0.0 mm for thickness at the time of the imaging.
•Once the 10% limit for subjects with tumor thickness growth rate ≥0.6 mm/year is reached (i.e., 10 subjects), additional eligible subjects with tumor thickness growth rate ≥0.6 mm/year will be considered as a screen failure.
7.Based on IRC measurements, the IL/CM has a thickness ≥0.5 mm and ≤2.5 mm on B-scan and LBD ≤10.0 mm on true-color FP.
8.Have a tumor for which the entire extent must be able to be imaged on true-color FP in a single frame and the tumor plus at least a 1 mm margin can be visualized per the IRC assessment.
9.Have a tumor that is posterior to the equator, i.e., anterior edge of the tumor is at or posterior to the equator per the IRC assessment.
10.If female and capable of becoming pregnant, agree to have pregnancy testing performed at screening (must be negative) and if required within 24 hours of investigational product (IP) administration (must be negative); and must agree to use and must agree to continue using such precautions for 90 days after the final dose of IP.
Note: Women considered capable of becoming pregnant include all females who have experienced menarche and have not experienced menopause (as defined by amenorrhea for greater than 12 consecutive months), have not undergone successful surgical sterilization (hysterectomy, bilateral ovariectomy, bilateral tubal ligation, or bilateral oophorectomy). A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly and includes:
a. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal).
b. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable).
c. Intrauterine device.
d. Intrauterine hormone-releasing system.
e. Bilateral tubal occlusion.
f. Vasectomized partner.
g. Sexual abstinence.
- Males of reproductive potential with sexual partners of childbearing potential must agree to use a highly effective form of birth control as outlined in the protocol or abstain from heterosexual activity before the administration of the IP and for 90 days after the final dose of the IP. Males should not donate sperm until 90 days after administration of the IP.
Note: Male subjects are considered to be of non-reproductive potential if they have azoospermia either from a vasectomy or from an underlying medical condition. A highly effective method of contraception is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly.
- Be able and willing to avoid all prohibited medications for the appropriate washout period.
Exclusion Criteria
Subject must not:
- Have in the Investigator’s opinion, any active ocular infection or ocular disease in the study eye (other than IL/CM) that may progress during the trial and result in a change in vision, loss in vision, confound the trial assessments, or alter the SCS (e.g., clinically significant corneal dystrophies, keratoconus, glaucoma or clinically significant choroidal, retinal, macular, or scleral disease). Subjects who have a known history of steroid induced glaucoma or high myopia (≥-6.00 diopters) are also excluded.
Notes:
a. Early background diabetic retinopathy should be discussed with the Medical Monitor prior to enrollment to confirm that the subject’s diabetes is considered to be well controlled (i.e., will not cause a change in ETDRS-BCVA) and will not confound trial results. Any evidence of diabetic macular edema on OCT is exclusionary.
b. Based on Investigator judgement subject has mild, early age-related macular degeneration (AMD). For the purposes of this study, this means that the subject may have small hard drusen, but should not have soft drusen, or any intermediate/large drusen (i.e., there may not be drusen greater than 50 microns, or confluent drusen) in either eye, and no geographic atrophy or history of choroidal neovascularization in either eye.
Note: Presence of drusen (including even soft, large, or confluent drusen) over top of the tumor is not exclusionary, IF the study site Investigator judges that these drusen are tumor-associated, and not related to underlying macular degeneration, when considering factors such as the location of the drusen relative to the macula, the location of the drusen relative to the tumor, and/or comparing between 2 eyes.
2.Have an IL/CM that is in contact with the optic disc ≥6 clock hours/≥180 degrees(based on true-color FP) per IRC or an IL/CM that invades the optic nerve per the Investigator’s judgement.
3.Have evidence of extraocular extension or evidence of a break in Bruch’s membrane(i.e., the tumor has spread outside the choroid) per the Investigator’s judgment.
4.Have undergone any ocular surgical intervention in the study eye within 3 months before Visit 1 or are planning/will require ocular surgery in the study eye during the trial. Subjects who have had an uncomplicated minor procedure or cataract surgery within 1-3 months of Visit 1 should be discussed on a case-by-case basis with the medical monitor for approval prior to enrollment. Laser surgery (e.g., refractive laser surgery, argon laser trabeculoplasty/ selective laser trabeculoplasty [ALT/SLT], and other minimally invasive surgeries [e.g., minimally invasive glaucoma surgery{MIGS}]) within 3 months of Visit 1 should be discussed with the medical monitor for approval prior to enrollment.
5.Have a history of any ocular surgery/procedure that could alter the SCS and affect SC administration of bel-sar (e.g., scleral buckle, laser retinopexy, macular laser, or pan-retinal photocoagulation).
6.Have an ETDRS-BCVA score worse than 65 letters in the study eye.
7.Use or require use of heparin or low molecular weight heparins within 1 week of any trial treatment or pentosan poly sulfate within a year prior to Visit 1.
8.Use or requires use of immunosuppressive or antineoplastic medications within 5half-lives of Visit 1. Steroids, including inhalation steroids, are permitted.
9.Any active malignancies other than IL/CM, or squamous or basal cell skin cancer. If there is evidence of clinical remission for at least 1 year, the subject’s eligibility should be discussed with the medical monitor for approval prior to enrollment.
10.Have any significant illness (e.g., an uncontrolled autoimmune disease, liver disease,severe cardiovascular disease [confirmed by a cardiologist], active infection, etc.) orclinically significant laboratory abnormalities that the Investigator determines couldinterfere with trial participation or put the subject at any unnecessary risk.
11.Have used an investigational drug or medical device within 30 days or 5 half-lives(whichever is longer) of Visit 1 or be concurrently enrolled in another IP trial.
12.Have known contraindications or sensitivities to phthalocyanine-based dye, the capsid component, or to prior treatment with laser.
