A Clinical Trial of Retinal Gene Therapy for X-linked Retinitis Pigmentosa Using BIIB112

NCT03116113 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 274RP1012016-003852-60
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 8

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).

Conditions

X-Linked Retinitis Pigmentosa

Keywords

XLRP; Ophthalmology; Gene Therapy; Retinitis Pigmentosa GTPase Regulator (RPGR); AAV8

Outcome Measures

Primary Outcomes (4)

• Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs)

  DLTs are defined as any of the following events considered to be related to study drug: Sustained decrease in best-corrected visual acuity (BCVA) of ≥30 letters on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart compared to baseline (sustained is defined as lasting 48 hours or more until recovery, with recovery defined as visual acuity (VA) returning to within 10 letters of baseline VA. An exception is made for surgery-related events occurring in close temporal association {within \<24 hours} of the surgery); Vitreous inflammation, vitritis (\>Grade 3 using standardized Nussenblatt vitreous inflammation scale grading); Any clinically significant retinal damage observed that is not directly attributed to complications of surgery; Any clinically relevant suspected unexpected serious adverse reaction, with the exception of vision loss or vision threatening.

  Up to Month 24

• Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs are defined as the AEs starting or worsening on or after the day of the first surgery.

  Day 0 (surgery) in Part 1 of the study up to 24 months

• Part 2: Percentage of Study Eyes With ≥7 Decibels (dB) Improvement From Baseline at ≥5 Points Out of the 16 Central Loci Points of the 10-2 Grid Assessed by Macular Integrity Assessment (MAIA) Microperimetry

  MAIA microperimetry assessment was measured in dB using a 10-2 grid of 68 points. Each point was labelled as '\< 0', '0', or a positive integer. The point labelled as '\< 0' was assigned a value of '-1' by MAIA in the calculation. Improvement in Retinal Sensitivity in center grid was defined as an increase from baseline of 7 or more dBs in any 5 or more points out of the 16 central points.

  Month 12

• Part 2: Number of Participants With TEAEs

  An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs are defined as AEs starting on or after the day of the first surgery.

  Day 0 (surgery) in Part 2 of the study up to 12 months

Secondary Outcomes (49)

• Part 1: Percentage of Study Eyes With ≥7 dB Improvement From Baseline at ≥5 Points Out of the 16 Central Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry

  Months 1, 3, 6, 9, 12, 18, and 24

• Part 1: Percentage of Study Eyes With ≥7 dB Improvement From Baseline at ≥5 Points Out of the 68 Loci Points of the 10-2 Grid Assessed by MAIA Microperimetry

  Months 1, 3, 6, 9, 12, 18, and 24

• Part 1: Change From Baseline in Mean Sensitivity of the 16 Central Loci Points Assessed by MAIA Microperimetry

  Baseline, Months 1, 3, 6, 9, 12, 18, and 24

• Part 1: Change From Baseline in Mean Sensitivity of the 68 Central Loci Points Assessed by MAIA Microperimetry

  Baseline, Months 1, 3, 6, 9, 12, 18, and 24

• Part 1: Change From Baseline in Mean Best Corrected Visual Acuity (BCVA) Reported as Letters

  Baseline, Months 1, 3, 6, 9, 12, 18, and 24

Study Arms (9)

Part 1: BIIB112 Dose 1

EXPERIMENTAL

Participants will receive a single Dose 1 of BIIB112 by sub-retinal injection on Day 0.

Biological: BIIB112

Part 1: BIIB112 Dose 2

EXPERIMENTAL

Participants will receive a single Dose 2 of BIIB112 by sub-retinal injection on Day 0.

Biological: BIIB112

Part 1: BIIB112 Dose 3

EXPERIMENTAL

Participants will receive a single Dose 3 of BIIB112 by sub-retinal injection on Day 0.

Biological: BIIB112

Part 1: BIIB112 Dose 4

EXPERIMENTAL

Participants will receive a single Dose 4 of BIIB112 by sub-retinal injection on Day 0.

Biological: BIIB112

Part 1: BIIB112 Dose 5

EXPERIMENTAL

Participants will receive a single Dose 5 of BIIB112 by sub-retinal injection on Day 0.

Biological: BIIB112

Part 1: BIIB112 Dose 6

EXPERIMENTAL

Participants will receive a single Dose 6 of BIIB112 by sub-retinal injection on Day 0.

Biological: BIIB112

Part 2: BIIB112 High Dose

EXPERIMENTAL

Participants will receive a single high dose of BIIB112 by sub-retinal injection.

Biological: BIIB112

Part 2: BIIB112 Low Dose

EXPERIMENTAL

Participants will receive a single low dose of BIIB112 by sub-retinal injection.

Biological: BIIB112

Part 2: Untreated Group

NO INTERVENTION

Participants will receive no intervention to allow for a controlled comparison.

Interventions

BIIB112 BIOLOGICAL

Administered as specified in the treatment arm.

Also known as: AAV8-RPGR

Part 1: BIIB112 Dose 1; Part 1: BIIB112 Dose 2; Part 1: BIIB112 Dose 3; Part 1: BIIB112 Dose 4; Part 1: BIIB112 Dose 5; Part 1: BIIB112 Dose 6; Part 2: BIIB112 High Dose; Part 2: BIIB112 Low Dose

Eligibility Criteria

• Age: 10 Years+
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biogen: lead

Study Sites (8)

Research Site

Gainesville, Florida, 32607, United States

Location

Research Site

Miami, Florida, 33136, United States

Location

Research Site

Portland, Oregon, 97239, United States

Location

Research Site

Philadelphia, Pennsylvania, 19104, United States

Location

Research Site

Dallas, Texas, 75231, United States

Location

Research Site

Manchester, United Kingdom

Location

Research Site

Oxford, United Kingdom

Location

Research Site

Southampton, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 32094925 RESULT

• Raji S, Taylor LJ, Josan AS, MacLaren RE, Cehajic-Kapetanovic J. Early-Onset Cone Photoreceptor Degeneration Is Associated With High Myopia in RPGR-Related Retinal Dystrophy. J Ophthalmol. 2025 Jun 11;2025:4244740. doi: 10.1155/joph/4244740. eCollection 2025.

  PMID: 40535564 DERIVED

• Lam BL, Pennesi ME, Kay CN, Panda S, Gow JA, Zhao G, MacLaren RE; XIRIUS Study Group. Assessment of Visual Function with Cotoretigene Toliparvovec in X-Linked Retinitis Pigmentosa in the Randomized XIRIUS Phase 2/3 Study. Ophthalmology. 2024 Sep;131(9):1083-1093. doi: 10.1016/j.ophtha.2024.02.023. Epub 2024 Feb 28.

  PMID: 38423215 DERIVED

• von Krusenstiern L, Liu J, Liao E, Gow JA, Chen G, Ong T, Lotery AJ, Jalil A, Lam BL, MacLaren RE; XIRIUS Part 1 Study GroupXOLARIS Study Group. Changes in Retinal Sensitivity Associated With Cotoretigene Toliparvovec in X-Linked Retinitis Pigmentosa With RPGR Gene Variations. JAMA Ophthalmol. 2023 Mar 1;141(3):275-283. doi: 10.1001/jamaophthalmol.2022.6254.

  PMID: 36757689 DERIVED

MeSH Terms

Conditions

Cone-Rod Dystrophy, X-Linked, Type 1

Interventions

Cotoretigene Toliparvovec

Results Point of Contact

• Title: US Biogen Clinical Trial Center
• Organization: Biogen

clinicaltrials@biogen.com

866-633-4636

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2017
• First Posted: April 14, 2017
• Study Start: March 8, 2017
• Primary Completion: November 18, 2020
• Study Completion: November 18, 2020
• Last Updated: January 18, 2024
• Results First Posted: January 18, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share

Locations

GB (3); US (5)