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

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ClinicalTrials.gov Identifier: NCT03913143
Recruitment Status : Recruiting
First Posted : April 12, 2019
Last Update Posted : March 11, 2020
Sponsor:
Information provided by (Responsible Party):
ProQR Therapeutics

Tracking Information
First Submitted Date  ICMJE February 21, 2019
First Posted Date  ICMJE April 12, 2019
Last Update Posted Date March 11, 2020
Actual Study Start Date  ICMJE April 4, 2019
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 11, 2019)
Mean change in BCVA after 12 months [ Time Frame: 12 months ]
Mean change in Best-corrected visual acuity (BCVA) relative to baseline after 12 months of treatment versus sham
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 11, 2019)
  • Percentage of subjects ≥-0.3 LogMAR change in BCVA vs sham [ Time Frame: 12 and 24 months ]
    Percentage of subjects with baseline BCVA ≥ 1.7 Logarithm of the minimum angle of resolution (LogMAR) with ≥ 0.3 LogMAR change in BCVA in treated versus sham
  • Percentage of subjects <1.7 Logmar with clinical meaningful improvement in mobility course score [ Time Frame: 12 and 24 months ]
    Percentage of subjects with baseline BCVA < 1.7 LogMAR with a clinically meaningful improvement in mobility course score in treated versus sham
  • Change in BCVA between two QR-110 dose groups [ Time Frame: 12 and 24 months ]
    Change in BCVA relative to baseline in the Dose 1 QR-110 dose group versus the dose 2 QR-110 dose group
  • Change in BCVA to baseline in pooled QR-110 subjects [ Time Frame: 12 and 24 months ]
    Change in BCVA in both QR-110 dose groups pooled relative to baseline
  • Change in mobility course score [ Time Frame: 12 and 24 months ]
    Change in mobility course score relative to baseline in the treatment eye versus sham
  • Change in mobility course score binocular vision [ Time Frame: 12 and 24 months ]
    Change in mobility course score binocular vision versus baseline versus sham
  • Rate of change in oculomotor instability from baseline [ Time Frame: 12 and 24 months ]
    Rate of change in oculomotor instability from baseline
  • Full-field light sensitivity threshold (FST) testing for white light from baseline [ Time Frame: 12 and 24 months ]
    Full-field light sensitivity threshold (FST) testing for white light from baseline
  • Full-field light sensitivity threshold (FST) testing for red light from baseline [ Time Frame: 12 and 24 months ]
    Full-field light sensitivity threshold (FST) testing for red light from baseline
  • Full-field light sensitivity threshold (FST) testing for blue light from baseline [ Time Frame: 12 and 24 months ]
    Full-field light sensitivity threshold (FST) testing for blue light from baseline
  • Change in photoreceptor inner/outer segment by OCT [ Time Frame: 12 and 24 months ]
    Change in photoreceptor inner segment/outer segment (inner segment [IS]/outer segment [OS]; ellipsoid zone [EZ] line) assessed by OCT relative to baseline
  • Change in patient reported visual function via VFQ-25 (adults) [ Time Frame: 12 and 24 months ]
    Change in patient reported visual function, as measured by the Visual Function Questionnaire-25 (VFQ-25) score for adult subjects relative to baseline
  • Change in patient reported visual function via CVAQC (pediatrics) [ Time Frame: 12 and 24 months ]
    Change in patient reported visual function, as measured by the Cardiff Visual Ability Questionnaire for Children (CVAQC) for pediatric subjects relative to baseline
  • Change in the Patient Global Impressions of Severity (PGI-S) [ Time Frame: 12 and 24 months ]
    Change in the patient-reported outcome (PRO) Patient Global Impressions of Severity (PGI-S)
  • Change in the Patient Global Impressions of Change (PGI-C) [ Time Frame: 12 and 24 months ]
    Change in the PRO Patient Global Impressions of Change (PGI-C)
  • Change in ERG [ Time Frame: 12 months ]
    Change in Electroretinogram (ERG) via International Society for Clinical Electrophysiology of Vision [ISCEV] standard for full-field clinical ERG) relative to baseline
  • Changes in ophthalmic examination findings [ Time Frame: 12 and 24 months ]
    Changes in ophthalmic examination findings
  • Severity of ocular AEs [ Time Frame: 12 and 24 months ]
    Severity of ocular AEs
  • Frequency of non-ocular AEs [ Time Frame: 12 and 24 months ]
    Frequency of non-ocular AEs
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE)
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Leber Congenital Amaurosis 10
  • Blindness
  • Leber Congenital Amaurosis
  • Vision Disorders
  • Sensation Disorders
  • Neurologic Manifestations
  • Eye Diseases
  • Eye Diseases, Hereditary
  • Eye Disorders Congenital
  • Retinal Disease
Intervention  ICMJE
  • Drug: sepofarsen
    RNA antisense oligonucleotide for intravitreal injection
    Other Name: QR-110
  • Other: Sham
    Sham intravitreal injection (no experimental drug administered)
Study Arms  ICMJE
  • Experimental: 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
    Intervention: Drug: sepofarsen
  • Active Comparator: 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
    Intervention: Drug: sepofarsen
  • Sham Comparator: Group 3: Sham
    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
    Intervention: Other: Sham
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 11, 2019)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 8 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: ProQR Clinical Trials Manager +31 (0)88 1667000 info@proqr.com
Listed Location Countries  ICMJE Belgium,   Canada,   France,   Germany,   Netherlands,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03913143
Other Study ID Numbers  ICMJE PQ-110-003
2018-003501-25 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party ProQR Therapeutics
Study Sponsor  ICMJE ProQR Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: ProQR Medical Monitor ProQR Therapeutics
PRS Account ProQR Therapeutics
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP