Primary: To determine the efficacy and safety of bel-sar compared to sham control for thetreatment of primary indeterminate lesions and small choroidal melanoma (IL/CM).Secondary: To assess the systemic pharmacokinetics (PK) and immunogenicity of…
ID
Source
Brief title
Condition
- Retina, choroid and vitreous haemorrhages and vascular disorders
- Ocular neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Time to reach Tumor Progression (at the Week 65 analysis).
Secondary outcome
Key Secondary:
*Time to reach Visual Acuity Failure 80 µg (at the Week 65 analysis).
*Time to reach Tumor Progression 80 µg (at the Week 104 analysis).
*Time to reach Visual Acuity Failure 80 µg (at the Week 104 analysis).
*Time to reach the Composite Endpoint 80 µg (at the Week 104 analysis).
*Time to reach Tumor Progression 40 µg (at the Week 65 analysis)
Background summary
Sponsor 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
investigational laser system (Modulight ML6710i Laser mady by Modulight
Corporation) for the treatment of choroidal melanoma (CM). Investigational
means that this treatment has not been approved as a marketed product (ie,
available to be prescribed or sold) by any regulatory authorities in The
Netherlands.
Study objective
Primary: To determine the efficacy and safety of bel-sar compared to sham
control for the
treatment of primary indeterminate lesions and small choroidal melanoma (IL/CM).
Secondary: To assess the systemic pharmacokinetics (PK) and immunogenicity of
bel-sar
with suprachoroidal (SC) administration.
Study design
This is a randomized, sham-controlled, subject-, assessor-, and Sponsor-masked
trial to establish
the efficacy and safety of bel-sar treatment via SC administration in subjects
with primary IL/CM.
Bel-sar treatment incorporates administration of bel-sar drug product using the
SCS Microinjector
and activation of bel-sar by a laser photoactivation device (Modulight ML6710i
Laser modified for
specific use with bel-sar). The trial will employ an enrichment strategy with
enrollment of subjects
with early documented growth of IL/CM. This will ensure that subjects have
actively growing
lesions allowing for a reduction in the variability of timing and event rates
of selected endpoints
being used to establish the efficacy of bel-sar treatment. The trial will be
conducted at sites that
evaluate and document tumor growth as part of their practice prior to treating
IL/CM. Subjects
with clinically diagnosed IL/CM, that have recent documented tumor growth for
whom
observation-only (i.e., a watchful waiting approach) could be an appropriate
SoC per Investigator's
judgment, will qualify for this trial.
Intervention
Once eligibility is confirmed, qualified subjects will be randomly assigned to
1 of 3 treatment arms
(80 µg bel-sar treatment arm, 40 µg bel-sar treatment arm, or sham control arm).
The bel-sar treatment arms will receive 3 cycles of treatment at the assigned
dose and the sham
control arm will receive 3 cycles of sham treatment. One cycle is defined as
once/week treatment
(bel-sar and laser for the 2 bel-sar treatment arms or sham injection and sham
laser for the sham
control arm) administered for 3 consecutive weeks (e.g., Cycle 1 treatments
will occur on Days 1,
8, and 15). Cycle 2 is planned to initiate at Week 4 and Cycle 3 at Week 8.
Study burden and risks
SCS Microinjector
According to the manufacturer of this microinjector, in controlled studies, the
most common ocular adverse reactions were increased intraocular pressure (IOP),
acute (6%), vitreous detachment (5%), injection site pain (4%) conjunctival
haemorrhage (4%), visual acuity reduced (4%), dry eye (3%), eye pain, acute
(3%), photophobia (3%), and vitreous floaters (3%), and in 2% of patients:
conjunctival hyperaemia, punctate keratitis, conjunctival oedema,
meibomianitis, anterior capsule contraction, chalazion, eye irritation, eye
pruritus, eyelid ptosis, photopsia, and vision blurred. The most common
non-ocular AE was headache (5%).
Photoactivation by Laser (Modulight ML6710i Laser)
Although they are rare, the laser treatment carries a few potential risks.
These include temporary vision changes such as blurred or decreased vision,
increased light sensitivity for a few days or weeks, and possible eye
discomfort or pain during or after the procedure.
While infection or inflammation are uncommon, they can occur at the treatment
site, necessitating further medical attention. Additionally, although extremely
rare, there is a slight risk of retinal detachment, indicated by symptoms like
increased floaters or flashes of light.
You may have side effects from the laser light application (or sham procedure).
You will be carefully monitored for any side effects. However, researchers do
not know all the side effects that may happen. Side effects may be mild or very
serious. Your health care team may give you medicines to help lessen side
effects. Many side effects go away soon after you stop receiving the laser or
sham procedure. In some cases, side effects can be serious, long lasting, or
may never go away. Call the investigator right away if you have, or believe you
may have, any side effects.
In an ongoing second study of bel-sar in which bel-sar was given by
suprachoroidal injection, 20 participants with eye melanoma have been enrolled
as of 03 February 2023. The most common side effects of laser treatment were
inflammation in the front of the eye, eye redness, eye pain, or irritation on
the cornea.
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US
Listed location countries
Age
Inclusion criteria
Ocular inclusion criteria apply to the study eye only unless specifically
stated otherwise.
Subject must:
1. Be at least 18 years of age.
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
would
be recommended standard of care.
Exclusion criteria
1. 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.
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 polysulfate within a year prior to Visit 1.
8. Use or requires use of immunosuppressive or antineoplastic medications
within 5
half-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.) or
clinically significant laboratory abnormalities that the Investigator
determines could
interfere 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.Have known
contraindications or sensitivities to phthalocyanine-based dye, the capsid
component, or to
prior treatment with laser.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL86304.000.24 |