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Study to Evaluate Safety and Tolerability of QR-421a in Subjects With RP Due to Mutations in Exon 13 of the USH2A Gene (Stellar)

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ClinicalTrials.gov Identifier: NCT03780257
Recruitment Status : Recruiting
First Posted : December 19, 2018
Last Update Posted : May 23, 2019
Sponsor:
Information provided by (Responsible Party):
ProQR Therapeutics

Tracking Information
First Submitted Date  ICMJE December 17, 2018
First Posted Date  ICMJE December 19, 2018
Last Update Posted Date May 23, 2019
Actual Study Start Date  ICMJE March 6, 2019
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 17, 2018)
  • Frequency and severity of ocular adverse events (AEs) in the treatment and contralateral eye [ Time Frame: 48 weeks ]
    Frequency and severity of ocular AEs
  • Frequency and severity of non-ocular AEs [ Time Frame: 48 weeks ]
    Frequency and severity of non-ocular AEs
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03780257 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 17, 2018)
  • Change in DAC VF [ Time Frame: 48 weeks ]
    Change in Dark Adapted Chromatic (DAC) Visual Field
  • Change in static VF [ Time Frame: 48 weeks ]
    Change in static Visual Field
  • Change in EZ area by OCT [ Time Frame: 48 weeks ]
    Change in Ellipsoid Zone (EZ) area by optical coherence tomography (OCT)
  • Change in BCVA [ Time Frame: 48 weeks ]
    Change in Best Corrected Visual Acuity (BCVA)
  • Change in semi-kinetic VF [ Time Frame: 48 weeks ]
    Change in semi-kinetic Visual Field
  • Change in microperimetry [ Time Frame: 48 weeks ]
    Change in microperimetry
  • Changes in ERG [ Time Frame: 48 weeks ]
    Changes in ERG ((International Society for Clinical Electrophysiology of Vision [ISCEV] standard for full-field clinical ERG)
  • Changes in NIRAF [ Time Frame: 48 weeks ]
    Changes in near-infrared autofluorescence (NIRAF)
  • AUC (0-∞) of QR-421a in serum [ Time Frame: 48 weeks ]
    Area under the curve 0 hour to infinity [AUC(0-∞)] of QR-421a in serum
  • AUC (0-tlast) of QR-421a in serum [ Time Frame: 48 weeks ]
    Area under the curve 0 hour to the final sample with a concentration greater than lower limit of quantification (LLOQ) [AUC(0-tlast)] of QR-421a in serum
  • Cmax of QR-421a in serum [ Time Frame: 48 weeks ]
    Maximum concentration (Cmax) of QR-421a in serum
  • Tmax of QR-421a [ Time Frame: 48 weeks ]
    Time to maximum concentration (Tmax) of QR-421a
  • T1/2 of QR-421a [ Time Frame: 48 weeks ]
    Terminal elimination half-life (T1/2) of QR-421a
  • Serum clearance (CL) of QR-421a [ Time Frame: 48 weeks ]
    Serum clearance (CL) of QR-421a
  • Volume of distribution (Vd) of QR-421a [ Time Frame: 48 weeks ]
    Volume of distribution (Vd) of QR-421a
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 Study to Evaluate Safety and Tolerability of QR-421a in Subjects With RP Due to Mutations in Exon 13 of the USH2A Gene
Official Title  ICMJE A First-in-Human Study to Evaluate the Safety and Tolerability of QR-421a in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
Brief Summary The purpose of this study is to evaluate the safety and tolerability of QR-421a administered via intravitreal injection (IVT) in subjects with Retinitis Pigmentosa (RP) due to mutations in exon 13 of the USH2A gene.
Detailed Description

The purpose of this study is to evaluate the safety and tolerability of QR-421a administered via IVT in subjects with RP due to mutations in exon 13 of the USH2A gene. Subjects will receive one single IVT injection of QR-421a or sham-procedure in one eye (subject's worse eye) and will be followed up for 48 weeks.

Three dose levels of QR-421a will be evaluated: 50, 100, and 200 µg. Additional dose levels (eg, 25 or 400 µg) may be evaluated based on ongoing safety and efficacy data monitoring.

Per dose cohort, a minimum of 4 subjects will be treated with QR-421a and a minimum of 2 subjects will receive the sham-procedure. The first subject in a dose cohort will receive QR-421a (open-label); subsequent subjects in the same dose cohort will be randomized to either QR-421a or sham-procedure.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
The first subject in a dose cohort will receive QR-421a (open-label); subsequent subjects in the same dose cohort will be randomized to either QR-421a or sham-procedure in a double-masked approach.
Primary Purpose: Treatment
Condition  ICMJE
  • Retinitis Pigmentosa
  • Usher Syndrome Type 2
  • Deaf Blind
  • Retinal Disease
  • Eye Diseases
  • Eye Diseases, Hereditary
  • Eye Disorders Congenital
  • Vision Disorders
Intervention  ICMJE
  • Drug: QR-421a
    RNA antisense oligonucleotide for intravitreal injection
    Other Name: RNA antisense oligonucleotide for intravitreal injection
  • Other: Sham-procedure
    Sham-procedure (no experimental drug administered)
Study Arms  ICMJE
  • Experimental: QR-421a
    Single dose administration
    Intervention: Drug: QR-421a
  • Sham Comparator: Sham-procedure
    Sham-procedure (no experimental drug administered)
    Intervention: Other: Sham-procedure
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: December 17, 2018)
18
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female, ≥ 18 years of age.
  2. Clinical presentation consistent with RP with Usher syndrome type 2 or non-syndromic RP (NSRP), based on ophthalmic, audiologic, and vestibular examinations.
  3. An ERG result consistent with RP with Usher syndrome type 2 or NSRP.
  4. A molecular diagnosis of homozygosity or compound heterozygosity for 1 or more pathogenic exon 13 mutations in the USH2A gene, based on genetic analysis upon Sponsor approval.
  5. A BCVA less than or equal to Logarithm of the Minimum Angle of Resolution (LogMAR) +0.2 in the worse eye.
  6. Semi-Automated Kinetic VF V4e (Octopus 900): Continuous area of central field greater than or equal to 10 degrees diameter (equivalent in area: 78.53981634 deg2) in both eyes.
  7. No limitations to OCT image collection that would prevent high quality, reliable images from being obtained in both eyes (including outer segment [OS] thickness and volume, outer nuclear layer [ONL] thickness, total receptor (TR) thickness, EZ horizontal and vertical widths, apparent continuous EZ area, central macula thickness [CMT], grading of cystic macular lesions [CML] if any), as determined by the reading center.
  8. Reliable perimetry measurements in both eyes, as described in the Study Reference Manual and determined by the reading center.
  9. Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging, as assessed by the Investigator.

Exclusion Criteria:

  1. Presence of additional non-exon 13 USH2A pathogenic mutation(s) on the USH2A allele carrying the exon 13 mutation in subjects who are compound heterozygous for mutations in exon 13.
  2. Presence of non-exon 13 USH2A pathogenic mutation(s) on both USH2A alleles in subjects who are homozygous for mutations in exon 13.
  3. Presence of pathogenic mutations in genes (other than the USH2A gene) associated with Usher syndrome Type 2 or NSRP, or other inherited retinal degenerative diseases or syndromes.
  4. Any contraindication to IVT injection according to the Investigator's clinical judgment and international guidelines.
  5. Nystagmus or unstable fixation.
  6. Amblyopia.
  7. Prior receipt of intraocular surgery or procedure or IVT injection within 12 weeks prior to study start or planned intraocular surgery or procedure during the course of the study.
  8. Any prior treatment with genetic therapy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: ProQR Clinical Trial Manager +31(0)88 166 7000 clinical@proqr.com
Listed Location Countries  ICMJE Belgium,   France,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03780257
Other Study ID Numbers  ICMJE PQ-421a-001
2018-002433-38 ( 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
Study Director: ProQR Clinical Trial Manager ProQR Therapeutics
PRS Account ProQR Therapeutics
Verification Date May 2019

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