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Study to Evaluate QR-110 in Subjects With Leber's Congenital Amaurosis (LCA) Due to the c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene

This study is not yet open for participant recruitment.
See Contacts and Locations
Verified May 2017 by ProQR Therapeutics
Sponsor:
Information provided by (Responsible Party):
ProQR Therapeutics
ClinicalTrials.gov Identifier:
NCT03140969
First received: May 1, 2017
Last updated: May 4, 2017
Last verified: May 2017
  Purpose
The purpose of this study is to evaluate the safety and tolerability of QR-110 administered via intravitreal injection in subjects with LCA due to the CEP290 p.Cys998X mutation.

Condition Intervention Phase
Leber's Congenital Amaurosis Drug: QR-110 Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Single Arm, Multiple Dose, Dose Escalation Study to Evaluate the Safety and Tolerability of QR-110 in Subjects With Leber's Congenital Amaurosis (LCA) Due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene

Resource links provided by NLM:


Further study details as provided by ProQR Therapeutics:

Primary Outcome Measures:
  • Frequency and severity of ocular adverse events in the treatment and contralateral eyes [ Time Frame: 1 year ]

Secondary Outcome Measures:
  • Frequency and severity of non-ocular adverse events [ Time Frame: 1 year ]
  • Change in ophthalmic examination findings [ Time Frame: 1 year ]
  • Change in best-corrected visual acuity (BCVA) [ Time Frame: 1 year ]
  • Change in infrared imaging [ Time Frame: 1 year ]
  • Change in optical coherence tomography (OCT) findings [ Time Frame: 1 year ]
  • Changes in safety parameters, including vital sign measurements, physical examination findings, ECG and laboratory parameters [ Time Frame: 1 year ]
  • Area under the curve 0 hour to infinity [AUC(0-∞)] of QR-110 in serum (if measurable) [ Time Frame: 1 year ]
  • Area under the curve 0 hour to time of the last measurable concentration [AUC(0-t)] of QR-110 in serum [ Time Frame: 1 year ]
  • Maximum concentration (Cmax ) of QR-110 in serum [ Time Frame: 1 year ]
  • Minimum concentration (Cmin) of QR-110 in serum [ Time Frame: 1 year ]
  • Time of maximum concentration (Tmax ) of QR-110 in serum [ Time Frame: 1 year ]
  • Terminal half life (T1/2) of QR-110 in serum (if measurable) [ Time Frame: 1 year ]
  • Clearance (CL) of QR-110 in serum (if measurable) [ Time Frame: 1 year ]
  • Volume of distribution (Vd) of QR-110 in serum (if measurable) [ Time Frame: 1 year ]
  • Change in full-field stimulus test (FST) [ Time Frame: 1 year ]
  • Change in pupillary light reflex (PLR) [ Time Frame: 1 year ]
  • Change in mobility course score [ Time Frame: 1 year ]

Estimated Enrollment: 12
Anticipated Study Start Date: June 2017
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: QR-110
Administered every 3 months
Drug: QR-110
RNA antisense oligonucleotide for intravitreal injection

Detailed Description:
The purpose of this study is to evaluate the safety and tolerability of QR-110 administered via intravitreal injection in subjects with LCA due to the CEP290 p.Cys998X mutation. Subjects will receive QR-110 in one eye every 3 months, for a maximum of 4 doses. Up to 3 dose levels of QR-110 will be evaluated.
  Eligibility

Ages Eligible for Study:   6 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, ≥ 6 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.
  • Best-corrected visual acuity greater than or equal to light perception in both eyes and equal to or worse than LogMAR +1.0 (Snellen notation 20/200) in the worse eye and equal to or worse than LogMAR +0.7 (Snellen notation 20/100) in the contralateral eye.
  • Detectable outer nuclear layer (ONL) in the area of the macula.
  • An electroretinogram (ERG) result consistent with LCA.
  • Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging.

Exclusion Criteria:

  • Syndromic disease.
  • Pregnant or breast-feeding female.
  • Any clinically significant cardiac disease or defect.
  • One or more coagulation parameters outside of the normal range.
  • Any ocular disease or condition that could compromise treatment safety, visual acuity or interfere with assessment of efficacy and safety.
  • Prior receipt of intraocular surgery or intravitreal 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-110-001 study period.
  • Any prior receipt of genetic therapy for LCA
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03140969

Contacts
Contact: Clinical Trial Manager +31 6 20 180 945 clinical@proqr.com

Locations
United States, Iowa
University of Iowa Not yet recruiting
Iowa City, Iowa, United States, 52242
Principal Investigator: Stephen R. Russell, MD         
United States, Pennsylvania
Scheie Eye Institute, University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: Artur V. Cideciyan, PhD         
Sub-Investigator: Samuel G. Jacobson, MD, PhD         
Belgium
Ghent University Hospital and Ghent University Not yet recruiting
Ghent, Belgium, B-9000
Principal Investigator: Bart P.R. Leroy, MD, PhD         
Sponsors and Collaborators
ProQR Therapeutics
Investigators
Study Director: ProQR Study Director ProQR Therapeutics
  More Information

Responsible Party: ProQR Therapeutics
ClinicalTrials.gov Identifier: NCT03140969     History of Changes
Other Study ID Numbers: PQ-110-001
2017-000813-22 ( EudraCT Number )
Study First Received: May 1, 2017
Last Updated: May 4, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ProQR Therapeutics:
CEP290
p.Cys998X
c.2991+1655A>G
RNA therapy
Antisense oligonucleotide
Leber's congenital amaurosis

Additional relevant MeSH terms:
Blindness
Leber Congenital Amaurosis
Vision Disorders
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Eye Diseases
Signs and Symptoms
Eye Diseases, Hereditary
Retinal Diseases

ClinicalTrials.gov processed this record on August 18, 2017