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

NCT03913143 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: PQ-110-0032018-003501-25
• Study Type: interventional
• Target: 36
• Locations: 9 countries
• Sites: 14

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

Conditions

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

Keywords

LCA10; CEP290; p.Cys998X; c.2991+1655A>G; Leber's Congenital Amaurosis; Antisense oligonucleotide; RNA therapy; QR-110; sepofarsen

Outcome Measures

Primary Outcomes (1)

• Change in BCVA

  Change in Best-corrected visual acuity (BCVA) relative to baseline after 12 months of treatment versus sham-procedure

  12 months

Secondary Outcomes (16)

• Change from baseline in BCVA ≤ -0.3 LogMAR

  12 and 24 months

• Clinical meaningful improvement in subjects with BCVA ≤ 1.7 LogMAR

  12 and 24 months

• Change in BCVA based on FrACT

  12 and 24 months

• Change in mobility course score

  12 and 24 months

• Change in ellipsoid zone (EZ) width/area assessed by SD-OCT

  12 and 24 months

Study Arms (3)

Group 1: Dose 1 sepofarsen (QR-110)

EXPERIMENTAL

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

Drug: sepofarsen

Group 2: Dose 2 sepofarsen (QR-110)

ACTIVE COMPARATOR

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

Drug: sepofarsen

Group 3: Sham

SHAM COMPARATOR

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

Other: Sham

Interventions

sepofarsen DRUG

RNA antisense oligonucleotide for intravitreal injection

Also known as: QR-110

Group 1: Dose 1 sepofarsen (QR-110); Group 2: Dose 2 sepofarsen (QR-110)

Sham OTHER

Sham-Procedure (no experimental drug administered)

Group 3: Sham

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.
• 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.
• Presence of any significant ocular or non-ocular disease/disorder (including medication and laboratory test abnormalities).

Sponsors & Collaborators

• ProQR Therapeutics: lead

Study Sites (14)

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Universitair Ziekenhuis Gent (UZ)

Ghent, Belgium

Location

INRET Clínica/ Santa Casa de Misericórdia de Belo Horizonte

Belo Horizonte, Minas Gerais, 30150270, Brazil

Location

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

São Paulo, São Paulo, 04023-062, Brazil

Location

The Hospital for Sick Children - SickKids

Toronto, Ontario, M5G 2L3, Canada

Location

McGill University Health Centre - Centre for Innovative Medicine

Montreal, Quebec, H4A 3J1, Canada

Location

Centre de maladies rares CHNO des Quinze Vingt

Paris, 75012, France

Location

Hospital Civil de Strasbourg

Strasbourg, 67091, France

Location

Justus-Liebig Universität - Department of Ophthalmology

Giessen, 35392, Germany

Location

University of Tuebingen - Inst. for Ophthalmic Research

Tübingen, 72076, Germany

Location

Eye Clinic University of Campania Luigi Vanvitelli

Naples, 80131, Italy

Location

Amsterdam University Medica Center - Locatie AMC

Amsterdam, 1105 AZ, Netherlands

Location

Het Oogziekenhuis Rotterdam

Rotterdam, 3011 BH, Netherlands

Location

Moorfields Eye Hospital - NHS Foundation Trust

London, EC1V 2PD, United Kingdom

Location

Related Links

• Sponsor website

MeSH Terms

Conditions

Leber Congenital Amaurosis 10; Blindness; Leber Congenital Amaurosis; Vision Disorders; Sensation Disorders; Neurologic Manifestations; Eye Diseases; Eye Diseases, Hereditary; Eye Abnormalities; Retinal Diseases; Meckel Syndrome, Type 4; Optic Atrophy, Hereditary, Leber

Interventions

salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Congenital Abnormalities; Optic Atrophies, Hereditary; Optic Atrophy; Optic Nerve Diseases; Cranial Nerve Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• ProQR Medical Monitor

  ProQR Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2019
• First Posted: April 12, 2019
• Study Start: April 4, 2019
• Primary Completion: January 31, 2022
• Study Completion: March 1, 2023
• Last Updated: March 17, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); NL (2); CA (2); IT (1); BR (2); US (1); GB (1); BE (1); FR (2)