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A Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using BIIB112 (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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03116113
Recruitment Status : Completed
First Posted : April 14, 2017
Last Update Posted : January 20, 2021
Sponsor:
Information provided by (Responsible Party):
Biogen ( NightstaRx Ltd, a Biogen Company )

Brief Summary:
The objective of the study is to evaluate the safety, tolerability and efficacy of a single sub-retinal injection of BIIB112 in participants with X-linked retinitis pigmentosa (XLRP).

Condition or disease Intervention/treatment Phase
X-Linked Retinitis Pigmentosa Biological: BIIB112 Phase 1 Phase 2

Detailed Description:
This study was previously posted by NightstaRx Ltd. In October, 2020, sponsorship of the trial was transferred to Biogen.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : March 16, 2017
Actual Primary Completion Date : November 18, 2020
Actual Study Completion Date : November 18, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1: BIIB112 Dose 1
Participants will receive a single Dose 1 of BIIB112 by sub-retinal injection on Day 0.
Biological: BIIB112
Administered as specified in the treatment arm
Other Name: AAV8-RPGR

Experimental: Part 1: BIIB112 Dose 2
Participants will receive a single Dose 2 of BIIB112 by sub-retinal injection on Day 0.
Biological: BIIB112
Administered as specified in the treatment arm
Other Name: AAV8-RPGR

Experimental: Part 1: BIIB112 Dose 3
Participants will receive a single Dose 3 of BIIB112 by sub-retinal injection on Day 0.
Biological: BIIB112
Administered as specified in the treatment arm
Other Name: AAV8-RPGR

Experimental: Part 1: BIIB112 Dose 4
Participants will receive a single Dose 4 of BIIB112 by sub-retinal injection on Day 0.
Biological: BIIB112
Administered as specified in the treatment arm
Other Name: AAV8-RPGR

Experimental: Part 1: BIIB112 Dose 5
Participants will receive a single Dose 5 of BIIB112 by sub-retinal injection on Day 0.
Biological: BIIB112
Administered as specified in the treatment arm
Other Name: AAV8-RPGR

Experimental: Part 1: BIIB112 Dose 6
Participants will receive a single Dose 6 of BIIB112 by sub-retinal injection on Day 0.
Biological: BIIB112
Administered as specified in the treatment arm
Other Name: AAV8-RPGR

Experimental: Part 2: BIIB112 High Dose
Participants will receive a single high dose of BIIB112 by sub-retinal injection.
Biological: BIIB112
Administered as specified in the treatment arm
Other Name: AAV8-RPGR

Experimental: Part 2: BIIB112 Low Dose
Participants will receive a single low dose of BIIB112 by sub-retinal injection.
Biological: BIIB112
Administered as specified in the treatment arm
Other Name: AAV8-RPGR

No Intervention: Part 2: Untreated Group
Participants will receive no intervention to allow for a controlled comparison.



Primary Outcome Measures :
  1. Part 1: Number of Participants with Dose-Limiting Toxicities (DLTs) [ Time Frame: Up to Month 24 ]
  2. Part 1: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to Month 24 ]
  3. Part 2: Percentage of Study Eyes with ≥7 Decibels (dB) Improvement from Baseline at ≥5 of the 16 Central Loci of the 10-2 Grid Assessed by Macular Integrity Assessment (MAIA) Microperimetry [ Time Frame: Months 12 ]
  4. Part 2: Number of Participants with TEAEs [ Time Frame: Up to Month 12 ]

Secondary Outcome Measures :
  1. Parts 1 and 2: Change from Baseline in Microperimetry [ Time Frame: Part 1: Month 1, 3, 6, 9, 12, 18 and 24; Part 2: Month 1, 2, 3, 6, 9, and 12 ]
  2. Parts 1 and 2: Change from Baseline in Visual Acuity as measured by Early Treatment of Diabetic Retinopathy Study (ETDRS) [ Time Frame: Part 1: Month 1, 3, 6, 9, 12, 18, and 24; Part 2: Month 1, 2, 3, 6, 9, and 12 ]
    Visual acuity will be assessed using Best Corrected Visual Acuity (BCVA) test. BCVA will be assessed for both eyes using the ETDRS visual acuity (VA) chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is to be reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.

  3. Part 1: Change from Baseline in Spectral Domain Optical Coherence Tomography (SD-OCT) [ Time Frame: Part 1: Month 1, 3, 6, 9, 12, 18 and 24 ]
  4. Part 1: Change from Baseline in Fundus Autofluorescence (AF) [ Time Frame: Part 1: Month 1, 3, 6, 12, 18 and 24 ]
  5. Part 1: Change from Baseline in Contrast Sensitivity [ Time Frame: Part 1: Month 3, 6, 12 and 24 ]
    Contrast sensitivity will be measured for both eyes, prior to pupil dilation, using a Pelli Robson chart.

  6. Part 2: Percentage of Study Eyes with an Improvement Over Baseline in the Central Area of the MAIA Microperimetry Grid [ Time Frame: Part 2: Month 1, 2, 3, 6 and 9 ]
  7. Part 2: Percentage of Study Eyes with an Improvement Over Baseline in the MAIA Microperimetry Grid. [ Time Frame: Part 2: Month 1, 2, 3, 6, 9 and 12 ]
  8. Part 2: Change from Baseline in Visual Field Assessed by Octopus 900 Perimeter [ Time Frame: Month 3, 6, and 12 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

Part 1:

  • Participants with genetically confirmed diagnosis of XLRP (with RPGR mutation).
  • Participant with active disease clinically visible within the macular region in both eyes.

Part 2:

- Participant with mean total retinal sensitivity in the study eye as assessed by microperimetry ≥ 0.1 dB and ≤8 dB.

Key exclusion Criteria:

Parts 1 and 2:

  • Participant with history of amblyopia in either eye.
  • Participated in a gene therapy trial previously or a clinical trial with an investigational drug in the past 12 weeks or received a gene/cell-based therapy at any time previously.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.


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): NCT03116113


Locations
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United States, Florida
Research Site
Gainesville, Florida, United States, 32607
Research Site
Miami, Florida, United States, 33136
United States, Oregon
Research Site
Portland, Oregon, United States, 97239
United States, Pennsylvania
Research Site
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Research Site
Dallas, Texas, United States, 75231
United Kingdom
Research Site
Manchester, United Kingdom
Research Site
Oxford, United Kingdom
Research Site
Southampton, United Kingdom
Sponsors and Collaborators
NightstaRx Ltd, a Biogen Company
Investigators
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Study Director: Medical Director Biogen
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: NightstaRx Ltd, a Biogen Company
ClinicalTrials.gov Identifier: NCT03116113    
Other Study ID Numbers: 274RP101 (NSR-RPGR-01)
First Posted: April 14, 2017    Key Record Dates
Last Update Posted: January 20, 2021
Last Verified: January 2021
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 Biogen ( NightstaRx Ltd, a Biogen Company ):
XLRP
Ophthalmology
Gene Therapy
Retinitis Pigmentosa GTPase Regulator (RPGR)
AAV8
Additional relevant MeSH terms:
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Retinitis
Retinitis Pigmentosa
Retinal Diseases
Eye Diseases
Eye Diseases, Hereditary
Retinal Dystrophies
Retinal Degeneration
Genetic Diseases, Inborn