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

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

Sponsors

Lead Sponsor: ProQR Therapeutics

Source ProQR Therapeutics
Brief 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

Detailed 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 may be initiated based on assessment of benefit/risk (including review of data from all clinical trials), and with concurrence of the Medical Monitor.

Overall Status Active, not recruiting
Start Date 2019-04-04
Completion Date 2021-12-01
Primary Completion Date 2021-12-01
Phase Phase 2/Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Mean change in BCVA after 12 months 12 months
Secondary Outcome
Measure Time Frame
Percentage of subjects ≥-0.3 LogMAR change in BCVA vs sham 12 and 24 months
Percentage of subjects <1.7 Logmar with clinical meaningful improvement in mobility course score 12 and 24 months
Change in BCVA between two QR-110 dose groups 12 and 24 months
Change in BCVA to baseline in pooled QR-110 subjects 12 and 24 months
Change in mobility course score 12 and 24 months
Change in mobility course score binocular vision 12 and 24 months
Rate of change in oculomotor instability from baseline 12 and 24 months
Full-field light sensitivity threshold (FST) testing for white light from baseline 12 and 24 months
Full-field light sensitivity threshold (FST) testing for red light from baseline 12 and 24 months
Full-field light sensitivity threshold (FST) testing for blue light from baseline 12 and 24 months
Change in photoreceptor inner/outer segment by OCT 12 and 24 months
Change in patient reported visual function via VFQ-25 (adults) 12 and 24 months
Change in patient reported visual function via CVAQC (pediatrics) 12 and 24 months
Change in the Patient Global Impressions of Severity (PGI-S) 12 and 24 months
Change in the Patient Global Impressions of Change (PGI-C) 12 and 24 months
Change in ERG 12 months
Changes in ophthalmic examination findings 12 and 24 months
Severity of ocular AEs 12 and 24 months
Frequency of non-ocular AEs 12 and 24 months
Enrollment 36
Condition
Intervention

Intervention Type: Drug

Intervention Name: sepofarsen

Description: RNA antisense oligonucleotide for intravitreal injection

Other Name: QR-110

Intervention Type: Other

Intervention Name: Sham

Description: Sham intravitreal injection (no experimental drug administered)

Arm Group Label: Group 3: Sham

Eligibility

Criteria:

Main Inclusion Criteria: - Male or female, ≥ 8 years of age at Screening with a clinical diagnosis of LCA and a molecular diagnosis of homozygosity or compound heterozygosity for the CEP290 p.Cys998X mutation, based on genotyping analysis at Screening. Historic genotyping results from a certified laboratory are acceptable with Sponsor approval. - BCVA greater or equal to Logarithm of the Minimum Angle of Resolution (LogMAR) +3.0, and equal 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: - Any contraindication to IVT injection according to the Investigator's clinical judgment and international guidelines (Avery 2014). - Any ocular and/or general disease or condition that could compromise subject's safety or interfere with assessment of efficacy and safety, as determined by the Investigator. - Prior receipt of intraocular surgery or IVT injection within 3 months prior to study start or planned intraocular surgery or procedure during the course of the study. - 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 therapy for LCA.

Gender:

All

Minimum Age:

8 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
ProQR Medical Monitor Study Director ProQR Therapeutics
Location
Facility:
University of Miami - Bascom Palmer Eye Institute | Miami, Florida, 33156, United States
University of Iowa | Iowa City, Iowa, 52242, United States
Columbia University Medical Center | New York, New York, 10032, United States
Casey Eye Institute - Oregon Health & Science University | Portland, Oregon, 97239-4197, United States
University of Pennsylvania - Center for Advanced Retinal & Ocular Therapeutics | Philadelphia, Pennsylvania, 19104, United States
Baylor College of Medicine | Houston, Texas, 77030, United States
Universitair Ziekenhuis Gent (UZ) | Ghent, Belgium
INRET Clínica/ Santa Casa de Misericórdia de Belo Horizonte | Belo Horizonte, MG, 30150270, Brazil
Federal University of São Paulo - Hospital São Paulo (UNIFESP-HSP) | São Paulo, SP, 04023-062, Brazil
The Hospital for Sick Children - SickKids | Toronto, Ontario, M5G 2L3, Canada
McGill University Health Centre - Centre for Innovative Medicine | Montréal, Quebec, H4A 3J1, Canada
Centre de maladies rares CHNO des Quinze Vingt | Paris, 75012, France
Hospital Civil de Strasbourg | Strasbourg, 67091, France
Justus-Liebig Universität - Department of Ophthalmology | Gießen, 35392, Germany
University of Tuebingen - Inst. for Ophthalmic Research | Tuebingen, 72076, Germany
Eye Clinic University of Campania Luigi Vanvitelli | Naples, 80131, Italy
Amsterdam University Medica Center - Locatie AMC | Amsterdam, 1105 AZ, Netherlands
Radboud Universitair Medisch Centrum | Nijmegen, 6525 GA, Netherlands
Het Oogziekenhuis Rotterdam | Rotterdam, 3011 BH, Netherlands
Moorfields Eye Hospital - NHS Foundation Trust | London, EC1V 2PD, United Kingdom
Location Countries

Belgium

Brazil

Canada

France

Germany

Italy

Netherlands

United Kingdom

United States

Verification Date

2020-12-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Label: Group 1: Dose 1 sepofarsen (QR-110)

Type: Experimental

Description: 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

Label: Group 2: Dose 2 sepofarsen (QR-110)

Type: Active Comparator

Description: 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

Label: Group 3: Sham

Type: Sham Comparator

Description: Sham Intravitreal Injection (no experimental drug administered), at month 0, month 3 and every six months there after. After 12 months cross over to active study drug may be initiated

Acronym ILLUMINATE
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

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