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A Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa (XIRIUS)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03116113
Recruitment Status : Recruiting
First Posted : April 14, 2017
Last Update Posted : April 21, 2020
Sponsor:
Information provided by (Responsible Party):
NightstaRx Ltd, a Biogen Company

Tracking Information
First Submitted Date  ICMJE March 29, 2017
First Posted Date  ICMJE April 14, 2017
Last Update Posted Date April 21, 2020
Actual Study Start Date  ICMJE March 16, 2017
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 4, 2019)
  • Part I: Incidence of dose limiting toxicities (DLTs) [ Time Frame: 24 months ]
    Proportion of patients with a DLT
  • Part I: Incidence of treatment emergent adverse events (TEAEs) [ Time Frame: 24 months ]
    Proportion of patients with a TEAE
  • Part II: Improvement from Baseline in microperimetry [ Time Frame: 12 Months ]
    Proportion of patients with improved microperimetry
  • Part II: The safety endpoint is incidence of TEAEs over a 12-month period [ Time Frame: 12 Months ]
    Proportion of patients with a TEAE
Original Primary Outcome Measures  ICMJE
 (submitted: April 13, 2017)
  • Incidence of dose limiting toxicities (DLTs) [ Time Frame: 12 months ]
    Proportion of patients with a DLT
  • Incidence of treatment emergent adverse events (TEAEs) [ Time Frame: 12 months ]
    Proportion of patients with a TEAE
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2020)
  • Best corrected visual acuity (BCVA) [ Time Frame: 24 Months (Part I),12 Months (Part II) ]
    ETDRS visual acuity chart
  • Microperimetry [ Time Frame: 24 Months (Part I),12 Months (Part II) ]
    Change in sensitivity (dB)
  • Spectral domain optical coherence tomography (SD-OCT) [ Time Frame: 24 Months (Part I) ]
    Ellipsoid Zone
  • Fundus autofluorescence (AF) [ Time Frame: 24 Months (Part I) ]
    To assess changes in the retina from baseline in autofluorescence imaging
  • Visual Fields [ Time Frame: 12 Months (Part II) ]
    Octopus 900 pro will be used to assess changes in central peripheral vison from baseline
Original Secondary Outcome Measures  ICMJE
 (submitted: April 13, 2017)
Change in best corrected visual acuity (BCVA) from baseline to Month 12 [ Time Frame: 12 months ]
BCVA will be assessed at each visit using the Early Treatment Diabetic Retinopathy Study (EDTRS) protocol. Missing post-baseline values will be imputed using last observation carried forward (LOCF) method.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa
Official Title  ICMJE A Dose Escalation (Phase 1), and Dose Expansion (Phase 2/3) Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using an Adeno-Associated Viral Vector (AAV8) Encoding Retinitis Pigmentosa GTPase Regulator (RPGR)
Brief Summary A clinical trial of AAV8-RPGR retinal gene therapy for patients with X-linked retinitis pigmentosa
Detailed Description This is a Phase 1/2/3, first-in-human, multi-centre, dose-escalation interventional study of AAV8-RPGR in male subjects with genetically confirmed XLRP. Part I is a dose-selection study; Part II is a dose-expansion study, comparing 2 doses, and a third untreated group to allow for a controlled comparison of efficacy and safety.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Part I unmasked,Part II masked. Outcomes assessor masked to treatment; subject, surgeon, investigator/site team, and sponsor masked to dose.
Primary Purpose: Treatment
Condition  ICMJE X-Linked Retinitis Pigmentosa
Intervention  ICMJE Biological: AAV8-RPGR
Comparison of different dosages of AAV8-RPGR
Study Arms  ICMJE
  • Experimental: Part I: Dose 1 AAV8-RPGR
    Single, subretinal administration of dose 1 as a single dose AAV8-RPGR
    Intervention: Biological: AAV8-RPGR
  • Experimental: Part I: Dose 2 AAV8-RPGR
    Single, subretinal administration of dose 2 as a single dose AAV8-RPGR
    Intervention: Biological: AAV8-RPGR
  • Experimental: Part I: Dose 3 AAV8-RPGR
    Single, subretinal administration of dose 3 as a single dose AAV8-RPGR
    Intervention: Biological: AAV8-RPGR
  • Experimental: Part I: Dose 4 AAV8-RPGR
    Single, subretinal administration of dose 4 as a single dose AAV8-RPGR
    Intervention: Biological: AAV8-RPGR
  • Experimental: Part I: Dose 5 AAV8-RPGR
    Single, subretinal administration of dose 5 as a single dose AAV8-RPGR
    Intervention: Biological: AAV8-RPGR
  • Experimental: Part I: Dose 6 AAV8-RPGR
    Single, subretinal administration of dose 6 as a single dose AAV8-RPGR
    Intervention: Biological: AAV8-RPGR
  • Experimental: Part II: High dose AAV8-RPGR
    Single, subretinal administration of high dose AAV8-RPGR
    Intervention: Biological: AAV8-RPGR
  • Experimental: Part II: Low dose AAV8-RPGR
    Single, subretinal administration of Low dose AAV8-RPGR
    Intervention: Biological: AAV8-RPGR
  • No Intervention: Part II: Untreated Group
    Untreated group to allow for a controlled comparison of efficacy and safety
Publications * Cehajic-Kapetanovic J, Xue K, Martinez-Fernandez de la Camara C, Nanda A, Davies A, Wood LJ, Salvetti AP, Fischer MD, Aylward JW, Barnard AR, Jolly JK, Luo E, Lujan BJ, Ong T, Girach A, Black GCM, Gregori NZ, Davis JL, Rosa PR, Lotery AJ, Lam BL, Stanga PE, MacLaren RE. Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Nat Med. 2020 Mar;26(3):354-359. doi: 10.1038/s41591-020-0763-1. Epub 2020 Feb 24.

*   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: March 4, 2019)
63
Original Estimated Enrollment  ICMJE
 (submitted: April 13, 2017)
24
Estimated Study Completion Date  ICMJE March 2021
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key inclusion Criteria:

  • Male
  • Part I: >= 18 years
  • Part II: >= 10 years
  • Documentation of a pathogenic mutation in the RPGR gene

Key exclusion Criteria:

  • Participated in a gene therapy trial previously or a clinical trial with an investigational drug in the past 12 weeks
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 10 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: NightstaRx Ltd, a Biogen Company +1 866-633-4636 clinicaltrials@biogen.com
Listed Location Countries  ICMJE United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03116113
Other Study ID Numbers  ICMJE NSR-RPGR-01
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 NightstaRx Ltd, a Biogen Company
Study Sponsor  ICMJE NightstaRx Ltd, a Biogen Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account NightstaRx Ltd, a Biogen Company
Verification Date April 2020

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