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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

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ClinicalTrials.gov Identifier: NCT03140969
Recruitment Status : Active, not recruiting
First Posted : May 4, 2017
Last Update Posted : September 20, 2018
Sponsor:
Information provided by (Responsible Party):
ProQR Therapeutics

Tracking Information
First Submitted Date  ICMJE May 1, 2017
First Posted Date  ICMJE May 4, 2017
Last Update Posted Date September 20, 2018
Actual Study Start Date  ICMJE October 16, 2017
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2017)
Frequency and severity of ocular adverse events in the treatment and contralateral eyes [ Time Frame: 1 year ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03140969 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 29, 2017)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2017)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE An Open-label, 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
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leber's Congenital Amaurosis
Intervention  ICMJE Drug: QR-110
RNA antisense oligonucleotide for intravitreal injection
Study Arms  ICMJE Experimental: QR-110
Administered every 3 months
Intervention: Drug: QR-110
Publications * Cideciyan AV, Jacobson SG, Drack AV, Ho AC, Charng J, Garafalo AV, Roman AJ, Sumaroka A, Han IC, Hochstedler MD, Pfeifer WL, Sohn EH, Taiel M, Schwartz MR, Biasutto P, Wit W, Cheetham ME, Adamson P, Rodman DM, Platenburg G, Tome MD, Balikova I, Nerinckx F, Zaeytijd J, Van Cauwenbergh C, Leroy BP, Russell SR. Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect. Nat Med. 2019 Feb;25(2):225-228. doi: 10.1038/s41591-018-0295-0. Epub 2018 Dec 17.

*   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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: May 3, 2017)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03140969
Other Study ID Numbers  ICMJE PQ-110-001
2017-000813-22 ( 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 Study Director ProQR Therapeutics
PRS Account ProQR Therapeutics
Verification Date September 2018

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