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

Eye Diseases Clinical Trial

— ILLUMINATE  

Official title:

Double-masked, Randomized, Controlled, Multiple-dose Study to Evaluate Efficacy, Safety, Tolerability and Syst. Exposure of QR-110 in Leber's Congenital Amaurosis (LCA) Due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03913143
• Other study ID #: PQ-110-003
• Secondary ID: 2018-003501-25
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: April 4, 2019
• Est. completion date: March 2023

Study information

• Verified date: February 2022
• Source: ProQR Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. completion date: March 2023
• Est. primary completion date: January 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years and older

Eligibility

Main Inclusion Criteria Relating to Study Initiation:

• 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.

Main Exclusion Criteria Relating to Study Initiation:

• 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.

Main Inclusion Criteria Relating to Treatment Initiation Contralateral Eye:

• 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.

Main Exclusion Criteria Relating to Treatment Initiation Contralateral Eye:

• 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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• sepofarsen
RNA antisense oligonucleotide for intravitreal injection

Other:
• Sham
Sham-Procedure (no experimental drug administered)

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Gent (UZ)	Ghent
Brazil	INRET Clínica/ Santa Casa de Misericórdia de Belo Horizonte	Belo Horizonte	MG
Brazil	Federal University of São Paulo - Hospital São Paulo (UNIFESP-HSP)	São Paulo	SP
Canada	McGill University Health Centre - Centre for Innovative Medicine	Montréal	Quebec
Canada	The Hospital for Sick Children - SickKids	Toronto	Ontario
France	Centre de maladies rares CHNO des Quinze Vingt	Paris
France	Hospital Civil de Strasbourg	Strasbourg
Germany	Justus-Liebig Universität - Department of Ophthalmology	Gießen
Germany	University of Tuebingen - Inst. for Ophthalmic Research	Tuebingen
Italy	Eye Clinic University of Campania Luigi Vanvitelli	Naples
Netherlands	Amsterdam University Medica Center - Locatie AMC	Amsterdam
Netherlands	Het Oogziekenhuis Rotterdam	Rotterdam
United Kingdom	Moorfields Eye Hospital - NHS Foundation Trust	London
United States	University of Iowa	Iowa City	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
ProQR Therapeutics

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Canada,  France,  Germany,  Italy,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in BCVA	Change in Best-corrected visual acuity (BCVA) relative to baseline after 12 months of treatment versus sham-procedure	12 months
Secondary	Change from baseline in BCVA = -0.3 LogMAR	Change from baseline in BCVA in subjects with BCVA better than 1.7 Logarithm of the minimum angle of resolution (LogMAR) at baseline	12 and 24 months
Secondary	Clinical meaningful improvement in subjects with BCVA = 1.7 LogMAR	Change from baseline in BCVA by a clinically meaningful improvement in subjects with BCVA equal to or worse than 1.7 LogMAR at baseline.	12 and 24 months
Secondary	Change in BCVA based on FrACT	Change from baseline in BCVA based on Freiburg visual acuity and contrast test (FrACT)	12 and 24 months
Secondary	Change in mobility course score	Change from baseline in mobility course score	12 and 24 months
Secondary	Change in ellipsoid zone (EZ) width/area assessed by SD-OCT	Change from baseline in ellipsoid zone (EZ) width/area assessed by SD-OCT	12 and 24 months
Secondary	Change in oculomotor instability (OCI)	Change in oculomotor instability from baseline	12 and 24 months
Secondary	Change in FST light sensitivity	Change from baseline in light sensitivity Full-field light sensitivity threshold (FST) testing (white, red, blue)	12 and 24 months
Secondary	Change in LLVA	Change from baseline in low luminance visual acuity (LLVA)	12 and 24 months
Secondary	Change in patient reported visual function via VFQ-25 (adults)	Change in patient reported visual function, as measured by the Visual Function Questionnaire-25 (VFQ-25) score for adult subjects relative to baseline	12 and 24 months
Secondary	Change in patient reported visual function via CVAQC (pediatrics)	Change in patient reported visual function, as measured by the Cardiff Visual Ability Questionnaire for Children (CVAQC) for pediatric subjects relative to baseline	12 and 24 months
Secondary	Change in the Patient Global Impressions of Severity (PGI-S)	Change in the patient-reported outcome (PRO) Patient Global Impressions of Severity (PGI-S)	12 and 24 months
Secondary	Change in the Patient Global Impressions of Change (PGI-C)	Change in the PRO Patient Global Impressions of Change (PGI-C)	12 and 24 months
Secondary	Change in FAF	Change from baseline as determined by fundus autofluorescence (FAF) imaging	12 and 24 months
Secondary	Changes in microperimetry	Change from baseline as determined by microperimetry	12 and 24 months
Secondary	Systemic exposure to QR-110	Systemic exposure to QR-110	12 and 24 months
Secondary	Ocular and non-ocular AEs	Frequency and severity of ocular and non-ocular AEs	12 and 24 months

External Links

•   Sponsor website