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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03913143
Recruitment Status : Active, not recruiting
First Posted : April 12, 2019
Last Update Posted : March 17, 2022
Sponsor:
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Leber Congenital Amaurosis 10 Blindness Leber Congenital Amaurosis Vision Disorders Sensation Disorders Neurologic Manifestations Eye Diseases Eye Diseases, Hereditary Eye Disorders Congenital Retinal Disease Drug: sepofarsen Other: Sham Phase 2 Phase 3

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 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : April 4, 2019
Actual Primary Completion Date : January 31, 2022
Estimated Study Completion Date : March 2023


Arm Intervention/treatment
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
Drug: sepofarsen
RNA antisense oligonucleotide for intravitreal injection
Other Name: QR-110

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
Drug: sepofarsen
RNA antisense oligonucleotide for intravitreal injection
Other Name: QR-110

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




Primary Outcome Measures :
  1. Change in BCVA [ Time Frame: 12 months ]
    Change in Best-corrected visual acuity (BCVA) relative to baseline after 12 months of treatment versus sham-procedure


Secondary Outcome Measures :
  1. Change from baseline in BCVA ≤ -0.3 LogMAR [ Time Frame: 12 and 24 months ]
    Change from baseline in BCVA in subjects with BCVA better than 1.7 Logarithm of the minimum angle of resolution (LogMAR) at baseline

  2. Clinical meaningful improvement in subjects with BCVA ≤ 1.7 LogMAR [ Time Frame: 12 and 24 months ]
    Change from baseline in BCVA by a clinically meaningful improvement in subjects with BCVA equal to or worse than 1.7 LogMAR at baseline.

  3. Change in BCVA based on FrACT [ Time Frame: 12 and 24 months ]
    Change from baseline in BCVA based on Freiburg visual acuity and contrast test (FrACT)

  4. Change in mobility course score [ Time Frame: 12 and 24 months ]
    Change from baseline in mobility course score

  5. Change in ellipsoid zone (EZ) width/area assessed by SD-OCT [ Time Frame: 12 and 24 months ]
    Change from baseline in ellipsoid zone (EZ) width/area assessed by SD-OCT

  6. Change in oculomotor instability (OCI) [ Time Frame: 12 and 24 months ]
    Change in oculomotor instability from baseline

  7. Change in FST light sensitivity [ Time Frame: 12 and 24 months ]
    Change from baseline in light sensitivity Full-field light sensitivity threshold (FST) testing (white, red, blue)

  8. Change in LLVA [ Time Frame: 12 and 24 months ]
    Change from baseline in low luminance visual acuity (LLVA)

  9. 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

  10. 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

  11. 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)

  12. 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)

  13. Change in FAF [ Time Frame: 12 and 24 months ]
    Change from baseline as determined by fundus autofluorescence (FAF) imaging

  14. Changes in microperimetry [ Time Frame: 12 and 24 months ]
    Change from baseline as determined by microperimetry

  15. Systemic exposure to QR-110 [ Time Frame: 12 and 24 months ]
    Systemic exposure to QR-110

  16. Ocular and non-ocular AEs [ Time Frame: 12 and 24 months ]
    Frequency and severity of ocular and non-ocular AEs



Information from the National Library of Medicine

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Ages Eligible for Study:   8 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03913143


Locations
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United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
Belgium
Universitair Ziekenhuis Gent (UZ)
Ghent, Belgium
Brazil
INRET Clínica/ Santa Casa de Misericórdia de Belo Horizonte
Belo Horizonte, MG, Brazil, 30150270
Federal University of São Paulo - Hospital São Paulo (UNIFESP-HSP)
São Paulo, SP, Brazil, 04023-062
Canada, Ontario
The Hospital for Sick Children - SickKids
Toronto, Ontario, Canada, M5G 2L3
Canada, Quebec
McGill University Health Centre - Centre for Innovative Medicine
Montréal, Quebec, Canada, H4A 3J1
France
Centre de maladies rares CHNO des Quinze Vingt
Paris, France, 75012
Hospital Civil de Strasbourg
Strasbourg, France, 67091
Germany
Justus-Liebig Universität - Department of Ophthalmology
Gießen, Germany, 35392
University of Tuebingen - Inst. for Ophthalmic Research
Tuebingen, Germany, 72076
Italy
Eye Clinic University of Campania Luigi Vanvitelli
Naples, Italy, 80131
Netherlands
Amsterdam University Medica Center - Locatie AMC
Amsterdam, Netherlands, 1105 AZ
Het Oogziekenhuis Rotterdam
Rotterdam, Netherlands, 3011 BH
United Kingdom
Moorfields Eye Hospital - NHS Foundation Trust
London, United Kingdom, EC1V 2PD
Sponsors and Collaborators
ProQR Therapeutics
Investigators
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Study Director: ProQR Medical Monitor ProQR Therapeutics
Additional Information:
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Responsible Party: ProQR Therapeutics
ClinicalTrials.gov Identifier: NCT03913143    
Other Study ID Numbers: PQ-110-003
2018-003501-25 ( EudraCT Number )
First Posted: April 12, 2019    Key Record Dates
Last Update Posted: March 17, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ProQR Therapeutics:
LCA10
CEP290
p.Cys998X
c.2991+1655A>G
Leber's Congenital Amaurosis
Antisense oligonucleotide
RNA therapy
QR-110
sepofarsen
Additional relevant MeSH terms:
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Blindness
Neurologic Manifestations
Vision Disorders
Sensation Disorders
Eye Diseases
Retinal Diseases
Leber Congenital Amaurosis
Eye Diseases, Hereditary
Eye Abnormalities
Genetic Diseases, Inborn
Disease
Pathologic Processes
Nervous System Diseases
Congenital Abnormalities