Primary: To evaluate safety and tolerability of sepofarsen in subjects with LCA10
ID
Source
Brief title
Condition
- Cytoplasmic disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Incidence and severity of ocular adverse events (AEs)
• Incidence and severity of non-ocular AEs.
Secondary outcome
Change from baseline to Month 12 in:
• BCVA
• Retinal sensitivity measured by FST (white, red, and blue)
Background summary
Leber congenital amaurosis caused by mutations in the CEP290 gene (LCA10) is a
severe inherited retinal degenerative disease resulting in blindness. In
patients with LCA10 due to the c.2991+1655A>G (p.Cys998X) mutation, visual
symptoms are usually detectable before 1 year of age. Patients show severe
vision impairment from an early age and in some cases further slowly
progressing loss of remaining vision. There are currently no approved therapies
for the treatment of LCA10 and therefore a high unmet medical need exists.
Available safety and efficacy data from trial PQ 110-001 (NCT03140969), a Phase
1b/2, open-label, multiple-dose, dose-escalation first-in-human trial to
evaluate the safety and tolerability of sepofarsen in subjects with LCA10 due
to the c.2991+1655A>G (p.Cys998X) mutation from the age of 8 years and older,
support the therapeutic potential observed in the nonclinical studies. A
pivotal Phase 2/3 trial in subjects of age 8 years and older is ongoing
(PQ-110-003). As the disease onset of LCA10 is in infancy and early childhood,
patients could potentially benefit from earlier initiation of treatment with
sepofarsen. This current trial PQ-110-005 will include subjects younger than 8
years of age to extend the data on safety and tolerability in this age group.
considering the individual subject*s response and the available safety
information.
Study objective
Primary: To evaluate safety and tolerability of sepofarsen in subjects with
LCA10 <8 years of age.
Secondary: To evaluate the effect of sepofarsen on structural and functional
ophthalmic outcome measures.
Study design
PQ-110-005 is An Open-Label, Dose Escalation and Double-Masked, Randomized,
Controlled Study to Evaluate the Safety and Tolerability of Sepofarsen in
Pediatric Subjects <8 Years of Age with Leber Congenital Amaurosis Type 10
(LCA10) due to the c.2991 +1655A>G (p.Cys998X) mutation.
Dose cohorts are planned using a staggered dose escalation design. The study
consists of two parts: an open-label dose escalation part, followed by a
double-masked randomized part. The current open label part will evaluate 3 dose
levels (cohorts). In the double-masked, randomized, controlled part of the
study, subjects will be randomized to 2 dose levels (cohorts). Subjects will
receive an unilateral IVT injection on Day 1. Thereafter a 6-monthly dosing
schedule is planned, considering the individual subject*s response.
Intervention
The study consists of two parts: an open-label dose escalation part, followed
by a double-masked randomized part. The current open label part will evaluate 3
dose levels (cohorts). In the double-masked, randomized, controlled part of the
study, subjects will be randomized to 2 dose levels (cohorts). Subjects will
receive an unilateral IVT injection on Day 1. Thereafter a 6-monthly dosing
schedule is planned, considering the individual subject*s response and the
available safety information.
Study burden and risks
In total there are 15 visits to the research center, with 4 telephone visits
in addition. The study drug will be administered via intravitreal injection. In
addition to the administration of the study drug, various tests are performed.
Subjects will receive a unilateral IVT injection of sepofarsen on Day 1.
Thereafter a 6-monthly dosing schedule is planned, considering the individual
subject*s response. The decision for any re-dosing and the decision on dose
level will be decided for each subject individually based on the ongoing data
monitoring by Investigator and Medical Monitor and, if appropriate, the DMC.
The dose level for re-dosing may therefore be different from the initial (dose
escalation phase) dose level.
Duration of Subject Participation is up to 27 months (up to 12 weeks screening;
24 months follow-up post first dose)
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Zernikedreef 9
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Listed location countries
Age
Inclusion criteria
1. Male or female child, <8 years of age at Screening
2. A clinical diagnosis of LCA and a molecular diagnosis of homozygosity or
compound heterozygosity for the c.2991+1655A>G mutation in the CEP290 gene,
based on genotyping analysis at Screening. Historic genotyping results from a
certified laboratory are acceptable with Sponsor approval.
3. BCVA equal to or better than Light Perception, and equal to or worse than
approximate Snellen equivalent 20/50 in the treatment eye.
4. Clear ocular media and adequate pupillary dilation to permit good quality
retinal imaging, as determined by the Investigator.
Exclusion criteria
1. Presence of pathogenic mutations in genes associated with other recessive,
dominant or X-linked inherited retinal degenerative diseases or syndromes based
on genetic analysis.
2. Presence of any significant ocular or non-ocular disease/disorder (including
medication abnormalities) which may either put the subject at risk because of
participation in the trial, may influence the results of the trial, or the
subject*s ability to participate in the trial.
3. Receipt within 1 month prior to Screening of any intraocular or periocular
surgery (including refractive surgery), or an IVT injection or planned
intraocular surgery or procedure during the course of the trial.
4. Current treatment or treatment within the past 3 months or planned treatment
with drugs known to be toxic to the lens, retina, or the optic nerve
5. Use of any investigational drug or device within 3 months or 5
half-lives of Day 1, whichever is longer, or plans to participate in another
study of a drug or device during the trial period.
6. Any prior receipt of genetic or stem-cell therapy for ocular or
non-ocular disease.
Design
Recruitment
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 |
|---|---|
| EudraCT | EUCTR2020-000535-45-NL |
| CCMO | NL74636.000.20 |