A Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE)

NCT ID: NCT03913143

Last Updated: 2022-03-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-04

Study Completion Date

2023-03-31

Brief Summary

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The purpose of this double-masked, randomized, controlled, multiple-dose study is to evaluate the efficacy, safety, tolerability and systemic exposure of sepofarsen (QR-110) administered via intravitreal injection in subjects with Leber's Congenital Amaurosis (LCA) due to the CEP290 p.Cys998X mutation after 24 months of treatment

Detailed Description

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The purpose of this double-masked, randomized, controlled, multiple-dose study is to evaluate the efficacy, safety, tolerability and systemic exposure of sepofarsen (QR-110) administered via intravitreal injection in subjects with Leber's Congenital Amaurosis (LCA) due to the CEP290 p.Cys998X mutation after 24 months of treatment.

At study start subjects will be randomized to one of 3 treatment groups with either active study drug or sham treatment.

Sepofarsen (QR-110) will be administered via intravitreal (IVT) injection into the subject's treatment eye (the subject's worse eye).

Subjects in the sham-procedure group will undergo a procedure that will closely mimic the active injection.

After each dosing subjects will be assessed for safety and tolerability at follow up visits.

After the first eye has been treated for at least 12 months, treatment of the contralateral eye and cross-over of subjects assigned to sham procedure may be initiated in eligible eyes (in a masked manner) based on assessment of benefit/risk (including review of data from all clinical trials), and with concurrence of the Medical Monitor.

Conditions

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Leber Congenital Amaurosis 10 Blindness Leber Congenital Amaurosis Vision Disorders Sensation Disorders Neurologic Manifestations Eye Diseases Eye Diseases, Hereditary Eye Disorders Congenital Retinal Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Group 1: Dose 1 sepofarsen (QR-110)

Initial loading dose, followed by maintenance doses at month 3 and every 6 months there after, administered by intravitreal injection (24 months duration of treatment). After 12 months treatment of the contralateral eye may be initiated

Group Type EXPERIMENTAL

sepofarsen

Intervention Type DRUG

RNA antisense oligonucleotide for intravitreal injection

Group 2: Dose 2 sepofarsen (QR-110)

Initial loading dose, followed by maintenance doses at month 3 and every 6 months there after, administered by intravitreal injection (24 months duration of treatment). After 12 months treatment of the contralateral eye may be initiated

Group Type ACTIVE_COMPARATOR

sepofarsen

Intervention Type DRUG

RNA antisense oligonucleotide for intravitreal injection

Group 3: Sham

Sham procedure (no experimental drug administered), Day 1, month 3 and every six months there after. After 12 months cross over to active study drug may be initiated

Group Type SHAM_COMPARATOR

Sham

Intervention Type OTHER

Sham-Procedure (no experimental drug administered)

Interventions

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sepofarsen

RNA antisense oligonucleotide for intravitreal injection

Intervention Type DRUG

Sham

Sham-Procedure (no experimental drug administered)

Intervention Type OTHER

Other Intervention Names

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QR-110

Eligibility Criteria

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Inclusion Criteria

* Male or female, ≥ 8 years of age at Screening with a clinical diagnosis of LCA10 and a molecular diagnosis of homozygosity or compound heterozygosity for the c.2991+1655A\>G mutation, based on genotyping analysis at Screening. A historic genotyping report from a certified laboratory is acceptable with Sponsor approval.
* BCVA better or equal to Logarithm of the Minimum Angle of Resolution (LogMAR) +3.0 (Hand Motion), and equal to or worse than LogMAR +0.4 in the treatment eye.
* Detectable outer nuclear layer (ONL) in the area of the macula.
* An electroretinogram (ERG) result consistent with LCA. A historic ERG result may be acceptable for eligibility.


* BCVA equal to or better than LP (logMAR +4), using the best BCVA reading at Month 12 and based on ETDRS or BRVT.
* Detectable outer nuclear layer (ONL) in the area of the macula.
* Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging.

Exclusion Criteria

* Presence of any significant ocular or non-ocular disease/disorder (including medication and laboratory test abnormalities).
* Prior receipt of intraocular surgery, periocular surgery, or IVT injection within 1 month prior to study start or planned intraocular surgery or procedure during the course of the study.Subjects who received an intraocular or periocular surgery between 1 to 3 months prior Screening, may only be considered for inclusion if there are no clinically significant complications of surgery present, and following approval by the Medical Monitor.
* History or presence of ocular herpetic diseases.
* Presence of any active ocular infection in the either eye.
* Presence of lens opacities/cataracts in the treatment eye.
* Current treatment or treatment within the past 12 months with therapies known to influence the immune system.
* History of glaucoma, or an IOP greater than 24 mmHg, at is not controlled with medication.
* History of amblyopia
* Use of any investigational drug or device within 90 days or 5 half-lives of Day 1, whichever is longer, or plans to participate in another study of a drug or device during the PQ-110-003 study period.
* Any prior receipt of genetic or stem-cell therapy.
* Known hypersensitivity to antisense oligonucleotides or any constituents of the injection.
* Pregnant and breastfeeding subjects.


* Presence of any significant ocular or non-ocular disease/disorder (including medication and laboratory test abnormalities).
* History or presence of ocular herpetic diseases.
* Presence of any active ocular infection in either eye.
* Presence of any lens opacities which are clinically significant, would adequately prevent clinical and photographic evaluation of the retina.
* A planned IVT injection or intraocular or periocular surgery/procedure (including refractive surgery) during the course of the study.
* A history of glaucoma or an IOP greater than 24 mmHg that is not controlled with medication.
* History of amblyopia.
* Plans to participate in another study of a drug or device during the study period.
* Pregnant and breastfeeding subjects.
Minimum Eligible Age

8 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ProQR Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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ProQR Medical Monitor

Role: STUDY_DIRECTOR

ProQR Therapeutics

Locations

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University of Iowa

Iowa City, Iowa, United States

Site Status

Universitair Ziekenhuis Gent (UZ)

Ghent, , Belgium

Site Status

INRET Clínica/ Santa Casa de Misericórdia de Belo Horizonte

Belo Horizonte, Minas Gerais, Brazil

Site Status

Federal University of São Paulo - Hospital São Paulo (UNIFESP-HSP)

São Paulo, São Paulo, Brazil

Site Status

The Hospital for Sick Children - SickKids

Toronto, Ontario, Canada

Site Status

McGill University Health Centre - Centre for Innovative Medicine

Montreal, Quebec, Canada

Site Status

Centre de maladies rares CHNO des Quinze Vingt

Paris, , France

Site Status

Hospital Civil de Strasbourg

Strasbourg, , France

Site Status

Justus-Liebig Universität - Department of Ophthalmology

Giessen, , Germany

Site Status

University of Tuebingen - Inst. for Ophthalmic Research

Tübingen, , Germany

Site Status

Eye Clinic University of Campania Luigi Vanvitelli

Naples, , Italy

Site Status

Amsterdam University Medica Center - Locatie AMC

Amsterdam, , Netherlands

Site Status

Het Oogziekenhuis Rotterdam

Rotterdam, , Netherlands

Site Status

Moorfields Eye Hospital - NHS Foundation Trust

London, , United Kingdom

Site Status

Countries

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United States Belgium Brazil Canada France Germany Italy Netherlands United Kingdom

Related Links

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http://www.proqr.com

Sponsor website

Other Identifiers

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2018-003501-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PQ-110-003

Identifier Type: -

Identifier Source: org_study_id

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