ChoroideremiaPhase 2GEMININCT03507686

A Safety Study of Retinal Gene Therapy for Choroideremia With Administration of BIIB111

A Phase 2 study testing BIIB111 in people with Choroideremia, run by Biogen at 6 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The objective of the study is to evaluate the safety of bilateral, sequential sub-retinal administration of a single dose of BIIB111 in adult male participants with Choroideremia (CHM). Read more about this study

Who is it for?: Ages 18 years and older, men only
Conditions the study is for: Choroideremia
What is being tested?: BIIB111
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 66 participants
Where: 6 sitesin 3 countries
Study dates: 29 Nov 2017to 29 Jun 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Men only
No healthy volunteers
Adult, Older adult

Who may be able to join

Are willing and able to give informed consent for participation in the study to have both eyes treated.
Have documentation of a genetically-confirmed diagnosis of CHM.
Have active disease clinically visible within the macular region of both eyes.
Have a BCVA of ≥34 ETDRS letters (20/200 or better Snellen acuity) in both eyes, or in the untreated eye, if the other eye was previously treated with BIIB111*
If previously treated with BIIB111 in an antecedent study, participants may be eligible for participation following Sponsor approval.
For participants who received treatment with BIIB111 in an antecedent study, have biological samples available to complete an adequate immunology profile.

Who cannot join

Have a history of amblyopia or inflammatory disorder in either eye.
Are unwilling to use barrier contraception methods or abstain from sexual intercourse for a period of 3 months following treatment with BIIB111 in either eye.
Have had previous intraocular surgery performed within 3 months of the Screening Visit in either eye.
Have any other significant ocular or non-ocular disease/disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the results of the study or the participant's ability to participate in the study. This includes but is not limited to a potential participants:
with a contraindication to oral corticosteroid (e.g., prednisolone/prednisone)
with clinically significant cataract in either eye

Show all 9Show fewer

who, in the clinical opinion of the Investigator, is not an appropriate candidate for sub-retinal surgery.
Have participated in another research study involving an investigational product in the past 12 weeks or received a gene/cell-based therapy at any time previously, except if treated within an antecedent study with BIIB111.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Trial locations and contacts

6 sites in 3 countries.

Country

City, postcode or hospital

6 sites in 3 countries

United States4 sites

Research Site
Boston, Massachusetts, 02114
Research Site
Cincinnati, Ohio, 45242
Research Site
Miami, Florida, 33136
Research Site
Portland, Oregon, 97239

Other trials in United States

France1 site

Research Site
Paris, 75571

Other trials in France

Germany1 site

Research Site
Tübingen, 72076

Other trials in Germany

About this study

Official title: An Open-Label Safety Study of Retinal Gene Therapy for Choroideremia With Bilateral, Sequential Administration of Adeno-Associated Viral Vector (AAV2) Encoding Rab Escort Protein 1 (REP1)

The objective of the study is to evaluate the safety of bilateral, sequential sub-retinal administration of a single dose of BIIB111 in adult male participants with Choroideremia (CHM).

Read the detailed description

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

Conditions: Choroideremia
Being tested: BIIB111
Keywords: NightstaRx, NSR-REP1, CHM, Gene Therapy, AAV, REP1, Timrepigene Emparvovec
Medical subject headings: Choroideremia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BIIB111Drug
Also called Gene Therapy, AAV2-REP1
Administered as specified in the treatment arm.

Study groups in NCT03507686
Study group	Role	What they receive
BIIB111	Experimental	Participants will receive a single dose of sub-retinal injection of BIIB111 in each eye at Day 0 separated by an interval of <6 months, 6-12 months, or >12 months. Receives: Drug: BIIB111

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Best-Corrected Visual Acuity (BCVA) as Measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) Chart in Letters at Month 12
BCVA was 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 reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eyes. 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.
Measured: Month 12
Ophthalmic Examination Assessment: Mean Intraocular Pressure (IOP) at Month 12
IOP, the fluid pressure inside the eye was measured and reported in millimeters mercury (mmHg).
Measured: Month 12
Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Slit Lamp Examination
Slit lamp examinations of study eyes included examination of Cornea, Conjunctiva, Iris, Lens, and Anterior Segment.
Measured: Baseline, Month 12
Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Dilated Ophthalmoscopy
Dilated Ophthalmoscopy examination of study eyes included examination of Vitreous, Macula, Peripheral retina, Choroid, and Optic nerve.
Measured: Baseline, Month 12
Ophthalmic Examination Assessment: Number of Participants With Lens Opacity Grading
The following lens opacity grades are reported for categories 1-4: Nuclear Opalescence grade, Nuclear Color grade, Cortical Cataract grade, and Posterior Cataract grade. Opacification severity is graded on a decimal scale, scores can range from 0.1 (no opacity) to 6.9 (maximum opacity) for the Nuclear Opalescence and Nuclear Color grades; and scores can range from 0.1 (lens clear) to 5.9 (lens unclear) for the Cortical and Posterior Cataract grades. Category 1 includes values 1, 1.0 and 0.x, Category 2 includes values 2, 2.0 and 1.x, Category 3 includes values 3, 3.0 and 2.x, and Category 4 includes values 4, 4.0, 3.x and any values above 4. For each opacification type the higher grading scores indicate greater severity.
Measured: Month 12
Spectral Domain Optical Coherence Tomography (SD-OCT): Foveal Subfield Thickness at Month 12
SD-OCT was used to assess change in foveal subfield thickness. The measurements were taken after dilation of the participant's pupil.
Measured: Month 12
SD-OCT: Total Macular Volume at Month 12
SD-OCT was used to assess change in total macular volume. The measurements were taken after dilation of the participant's pupil.
Measured: Month 12
SD-OCT: Central Horizontal Ellipsoid Width at Month 12
SD-OCT was used to assess change in central horizontal ellipsoid width. The measurements were taken after dilation of the participant's pupil.
Measured: Month 12
SD-OCT: Central Ellipsoid Area at Month 12
SD-OCT was used to assess change in central ellipsoid area. The measurements were taken after dilation of the participant's pupil.
Measured: Month 12
SD-OCT: Square Root of Central Ellipsoid Area at Month 12
SD-OCT was used to assess change in square root of central ellipsoid area. The measurements were taken after dilation of the participant's pupil.
Measured: Month 12
SD-OCT: Choroidal Thickness at Foveal Center at Month 12
SD-OCT was used to assess change in choroidal thickness. The measurements were taken after dilation of the participant's pupil.
Measured: Month 12
Fundus Autofluorescence (AF): Mean Total Area of Preserved Autofluorescence at Month 12
Fundus AF was used to assess the total area of preserved AF. Areas of preserved AF were identified as well-demarcated regions of relative hyper autofluorescence (hyper AF) compared with the background areas of surrounding atrophy.
Measured: Month 12
AF: Mean Square Root of Total Area of Preserved AF at Month 12
Fundus AF was used to assess the square root of total area of preserved AF. Areas of preserved AF were identified as well-demarcated regions of relative hyper AF compared with the background areas of surrounding atrophy.
Measured: Month 12
AF: Mean Distance From Foveal Center to Nearest Border of Preserved AF at Month 12
Fundus AF was used to assess the distance from foveal center to nearest border of preserved AF.
Measured: Month 12
Fundus Photography: Number of Participants With Retinal Pigment Epithelium (RPE) Hyperplasia as Per Severity
Number of participants with RPE hyperplasia are reported for severity grades: mild, moderate, severe.
Measured: Month 12
Fundus Photography: Number of Participants With Retinal Arteriolar Narrowing as Per Severity
Number of participants with retinal arteriolar narrowing are reported for severity grades: mild, moderate, severe.
Measured: Month 12
Fundus Photography: Number of Participants With Retinal Vessel Sheathing as Per Severity
Number of participants with retinal vessel sheathing are reported for severity grades: mild, moderate, severe.
Measured: Month 12
Fundus Photography: Number of Participants With Optic Atrophy/Pallor as Per Severity
Number of participants with optic atrophy/pallor are reported for severity grades: mild, moderate, severe.
Measured: Month 12
Fundus Photography: Number of Participants With Optic Disc Swelling as Per Severity
Number of participants with optic disc swelling are reported for severity grades: mild, moderate, severe.
Measured: Month 12
Microperimetry: Retinal Mean Sensitivity at Month 12
Microperimetry was conducted to assess retinal mean sensitivity within the macula. Retinal mean sensitivity to light was measured in decibels in multiple spots across the central and peripheral retina (entire visual field). Higher numbers (decibels) indicate higher retinal sensitivity.
Measured: Month 12
Microperimetry: Bivariate Contour Ellipse Area 63% at Month 12
Microperimetry was conducted to assess bivariate contour ellipse area 63%.
Measured: Month 12
Microperimetry: Bivariate Contour Ellipse Area 95% at Month 12
Microperimetry was conducted to assess bivariate contour ellipse area 95%.
Measured: Month 12
Microperimetry: Fixation Losses (in Percentage) at Month 12
Microperimetry was conducted to assess fixation losses (in percentage) which samples the optic nerve blind spot for positive responses.
Measured: Month 12
Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
An AE is any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug/surgical procedure, whether or not related to the investigational product or with the surgical procedure. TEAEs are defined as AEs starting on or after the day of the first surgery.
Measured: Day 0 (surgery) in period 1 up to last follow up visit in period 2 (approximately 2 years)
Number of Participants With Vector Shedding Post-treatment at Month 3
Tears (for both eyes- oculus dexter [OD] and oculus sinister [OS]), blood, urine and saliva samples were collected and tested using an appropriate assay for evidence of vector shedding. Participants with positive result for vector shredding post treatment are reported.
Measured: Baseline, at Month 3
Number of Participants With Anti-drug Antibodies Post-treatment at Month 12
Participants with antibodies to the REP-1 transgenic product are reported.
Measured: Month 12
Vital Signs: Change From Baseline in Blood Pressure at Month 12
Change from baseline in Systolic and diastolic blood pressures (BP) (millimeters of mercury [mmHg]) were reported.
Measured: Baseline, Month 12
Vital Signs: Change From Baseline in Pulse Rate at Month 12
Change from baseline in pulse rate (beats per minute) were reported.
Measured: Baseline, Month 12

Secondary outcomes (14)

Change From Baseline in BCVA as Measured by the ETDRS Chart
BCVA was assessed for both eyes using the ETDRS 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 reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eyes. The lower the number of letters read correctly on the eye chart, the worse the vision (or VA). An increase in the number of letters read correctly means that vision has improved.
Measured: Baseline, Month 12
AF: Change From Baseline in Total Area of Preserved Autofluorescence at Month 12
Fundus AF was used to assess change in total area of preserved AF. Areas of preserved AF were identified as well-demarcated regions of relative hyper autofluorescence (hyper AF) compared with the background areas of surrounding atrophy. Here negative values indicate decline in total area of preserved autofluoroscence.
Measured: Baseline, Month 12
AF: Change From Baseline in Square Root of Total Area of Preserved AF at Month 12
Fundus AF was used to assess change in square root of total area of preserved AF. Areas of preserved AF were identified as well-demarcated regions of relative hyper AF compared with the background areas of surrounding atrophy. Here negative values indicate decline in total area of preserved autofluoroscence.
Measured: Baseline, Month 12
AF: Change From Baseline in Distance From Foveal Center to Nearest Border of Preserved AF at Month 12
Fundus Autofluoroscence was used to assess change in distance from foveal center to nearest border of preserved autofluoroscence. Here negative values indicate decline in total area of preserved autofluoroscence.
Measured: Baseline, Month 12
SD-OCT: Change From Baseline in Foveal Subfield Thickness at Month 12
SD-OCT was used to assess change in foveal subfield thickness. The measurements were taken after dilation of the participant's pupil. A negative change from baseline indicates decline in foveal subfield thickness.
Measured: Baseline, Month 12
SD-OCT: Change From Baseline in Total Macular Volume at Month 12
SD-OCT was used to assess change in total macular volume. The measurements were taken after dilation of the participant's pupil. A negative change from baseline indicates decline in total macular volume.
Measured: Baseline, Month 12
SD-OCT: Change From Baseline in the Central Horizontal Ellipsoid Width at Month 12
SD-OCT was used to assess change in central horizontal ellipsoid width. The measurements were taken after dilation of the participant's pupil. A negative change from baseline indicates decline in central horizontal ellipsoid width.
Measured: Baseline, Month 12
SD-OCT: Change From Baseline in Central Ellipsoid Area at Month 12
SD-OCT was used to assess change in central ellipsoid area. The measurements were taken after dilation of the participant's pupil. A negative change from baseline indicates decline in central ellipsoid area.
Measured: Baseline, Month 12
SD-OCT: Change From Baseline in Square Root of Central Ellipsoid Area at Month 12
SD-OCT was used to assess change in square root of central ellipsoid area. The measurements were taken after dilation of the participant's pupil. A negative change from baseline indicates decline in square root of central ellipsoid area.
Measured: Baseline, Month 12
SD-OCT: Change From Baseline in the Choroidal Thickness at Foveal Center at Month 12
SD-OCT was used to assess change in choroidal thickness. The measurements were taken after dilation of the participant's pupil. A negative change from baseline indicates decline in choroidal thickness.
Measured: Baseline, Month 12
Microperimetry: Change From Baseline in Retinal Mean Sensitivity at Month 12
Microperimetry was conducted to assess change in retinal mean sensitivity within the macula. Retinal mean sensitivity to light was measured in decibels in multiple spots across the central and peripheral retina (entire visual field). Higher numbers (decibels) indicate higher retinal sensitivity. A negative change from baseline indicates decline in retinal sensitivity.
Measured: Baseline, Month 12
Microperimetry: Change From Baseline in Bivariate Contour Ellipse Area 63% at Month 12
Microperimetry was conducted to assess change in bivariate contour ellipse area 63%. A negative change from baseline indicates decline in bivariate contour ellipse area 63%.
Measured: Baseline, Month 12
Microperimetry: Change From Baseline in the Bivariate Contour Ellipse Area 95% at Month 12
Microperimetry was conducted to assess change in bivariate contour ellipse area 95%. A negative change from baseline indicates decline in bivariate contour ellipse area 95%.
Measured: Baseline, Month 12
Microperimetry: Change From Baseline in Fixation Losses (in Percentage) at Month 12
Microperimetry was conducted to assess change in fixation losses (in percentage) which samples the optic nerve blind spot for positive responses. A negative change from baseline indicates decline in fixation losses.
Measured: Baseline, Month 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Nov 201729 Jun 2022

First posted25 Apr 2018
Study start29 Nov 2017
Primary completion29 Jun 2022
Study completion29 Jun 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for ChoroideremiaStudies of the same condition, open and under way.
More trials run by BiogenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 66 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03507686
Sponsor's protocol ID: 273CH203
Other IDs: 2017-002395-75, 2017
Acronym: GEMINI
Status last verified: Aug 2023
First submitted: 7 Mar 2018
Last updated: 23 Feb 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

MacLaren RE, Audo I, Fischer MD, Huckfeldt RM, Lam BL, Pennesi ME, Sisk R, Gow JA, Li J, Zhu K, Tsang SF. An Open-Label Phase II Study Assessing the Safety of Bilateral, Sequential Administration of Retinal Gene Therapy in Participants with Choroideremia: The GEMINI Study. Hum Gene Ther. 2024 Aug;35(15-16):564-575. doi: 10.1089/hum.2024.017. Epub 2024 Jul 27.
PubMed 38970425
Davis JL. The Blunt End: Surgical Challenges of Gene Therapy for Inherited Retinal Diseases. Am J Ophthalmol. 2018 Dec;196:xxv-xxix. doi: 10.1016/j.ajo.2018.08.038. Epub 2018 Sep 5.
PubMed 30194931

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Inherited Retinal Degenerative Disease Registry
Eye Diseases Hereditary, Retinal Disease
RecruitingObservational study
High Resolution Retinal Imaging
Stargardts, Retinitis Pigmentosa
Active, not recruitingPhase 1
Study to Evaluate Safety of RTx-015 Injection in Retinitis Pigmentosa or Choroideremia Patients (ENVISION)
Retinitis Pigmentosa, Choroideremia
Recruiting
HYPER MIND - Hyperoxia Effects on Cerebral Hemodynamics
Hyperoxemia, Cerebrovascular Circulation
Active, not recruitingPhase 1
Dose Escalation Study of Intravitreal 4D-110 in Patients With Choroideremia
Choroideremia

All Choroideremia trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label Safety Study of Retinal Gene Therapy for Choroideremia With Bilateral, Sequential Administration of Adeno-Associated Viral Vector (AAV2) Encoding Rab Escort Protein 1 (REP1)
ClinicalTrials.gov ID: NCT03507686
Acronym / sponsor ID: GEMINI / 273CH203
Conditions: Choroideremia
Keywords: NightstaRx, NSR-REP1, CHM, Gene Therapy, AAV, REP1, Timrepigene Emparvovec
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 66 participants (actual)
Lead sponsor: BiogenIndustry (pharma, biotech, devices)
Study start: 29 Nov 2017 (actual)
Primary completion: 29 Jun 2022 (actual)
Study completion: 29 Jun 2022 (actual)
First posted: 25 Apr 2018 (actual)
Results: Posted 18 Sep 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The objective of the study is to evaluate the safety of bilateral, sequential sub-retinal administration of a single dose of BIIB111 in adult male participants with Choroideremia (CHM).

Detailed description

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

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
BIIB111	Experimental	Drug: BIIB111Participants will receive a single dose of sub-retinal injection of BIIB111 in each eye at Day 0 separated by an interval of <6 months, 6-12 months, or >12 months.

Who may qualify

Ages: 18 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Are willing and able to give informed consent for participation in the study to have both eyes treated.
Have documentation of a genetically-confirmed diagnosis of CHM.
Have active disease clinically visible within the macular region of both eyes.
Have a BCVA of ≥34 ETDRS letters (20/200 or better Snellen acuity) in both eyes, or in the untreated eye, if the other eye was previously treated with BIIB111*
If previously treated with BIIB111 in an antecedent study, participants may be eligible for participation following Sponsor approval.

Key exclusion criteria (9 listed)

Have a history of amblyopia or inflammatory disorder in either eye.
Are unwilling to use barrier contraception methods or abstain from sexual intercourse for a period of 3 months following treatment with BIIB111 in either eye.
Have had previous intraocular surgery performed within 3 months of the Screening Visit in either eye.
Have any other significant ocular or non-ocular disease/disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the results of the study or the participant's ability to participate in the study. This includes but is not limited to a potential participants:
Have participated in another research study involving an investigational product in the past 12 weeks or received a gene/cell-based therapy at any time previously, except if treated within an antecedent study with BIIB111.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BIIB111Also: Gene Therapy, AAV2-REP1Administered as specified in the treatment arm.	Drug	BIIB111

Primary outcome

Mean Best-Corrected Visual Acuity (BCVA) as Measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) Chart in Letters at Month 12
Time frame: Month 12
BCVA was 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 reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eyes. 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.
Ophthalmic Examination Assessment: Mean Intraocular Pressure (IOP) at Month 12
Time frame: Month 12
IOP, the fluid pressure inside the eye was measured and reported in millimeters mercury (mmHg).
Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Slit Lamp Examination
Time frame: Baseline, Month 12
Slit lamp examinations of study eyes included examination of Cornea, Conjunctiva, Iris, Lens, and Anterior Segment.
Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Dilated Ophthalmoscopy
Time frame: Baseline, Month 12
Dilated Ophthalmoscopy examination of study eyes included examination of Vitreous, Macula, Peripheral retina, Choroid, and Optic nerve.
Ophthalmic Examination Assessment: Number of Participants With Lens Opacity Grading
Time frame: Month 12
The following lens opacity grades are reported for categories 1-4: Nuclear Opalescence grade, Nuclear Color grade, Cortical Cataract grade, and Posterior Cataract grade. Opacification severity is graded on a decimal scale, scores can range from 0.1 (no opacity) to 6.9 (maximum opacity) for the Nuclear Opalescence and Nuclear Color grades; and scores can range from 0.1 (lens clear) to 5.9 (lens unclear) for the Cortical and Posterior Cataract grades. Category 1 includes values 1, 1.0 and 0.x, Category 2 includes values 2, 2.0 and 1.x, Category 3 includes values 3, 3.0 and 2.x, and Category 4 includes values 4, 4.0, 3.x and any values above 4. For each opacification type the higher grading scores indicate greater severity.
Spectral Domain Optical Coherence Tomography (SD-OCT): Foveal Subfield Thickness at Month 12
Time frame: Month 12
SD-OCT was used to assess change in foveal subfield thickness. The measurements were taken after dilation of the participant's pupil.
SD-OCT: Total Macular Volume at Month 12
Time frame: Month 12
SD-OCT was used to assess change in total macular volume. The measurements were taken after dilation of the participant's pupil.
SD-OCT: Central Horizontal Ellipsoid Width at Month 12
Time frame: Month 12
SD-OCT was used to assess change in central horizontal ellipsoid width. The measurements were taken after dilation of the participant's pupil.
SD-OCT: Central Ellipsoid Area at Month 12
Time frame: Month 12
SD-OCT was used to assess change in central ellipsoid area. The measurements were taken after dilation of the participant's pupil.
SD-OCT: Square Root of Central Ellipsoid Area at Month 12
Time frame: Month 12
SD-OCT was used to assess change in square root of central ellipsoid area. The measurements were taken after dilation of the participant's pupil.
SD-OCT: Choroidal Thickness at Foveal Center at Month 12
Time frame: Month 12
SD-OCT was used to assess change in choroidal thickness. The measurements were taken after dilation of the participant's pupil.
Fundus Autofluorescence (AF): Mean Total Area of Preserved Autofluorescence at Month 12
Time frame: Month 12
Fundus AF was used to assess the total area of preserved AF. Areas of preserved AF were identified as well-demarcated regions of relative hyper autofluorescence (hyper AF) compared with the background areas of surrounding atrophy.
AF: Mean Square Root of Total Area of Preserved AF at Month 12
Time frame: Month 12
Fundus AF was used to assess the square root of total area of preserved AF. Areas of preserved AF were identified as well-demarcated regions of relative hyper AF compared with the background areas of surrounding atrophy.
AF: Mean Distance From Foveal Center to Nearest Border of Preserved AF at Month 12
Time frame: Month 12
Fundus AF was used to assess the distance from foveal center to nearest border of preserved AF.
Fundus Photography: Number of Participants With Retinal Pigment Epithelium (RPE) Hyperplasia as Per Severity
Time frame: Month 12
Number of participants with RPE hyperplasia are reported for severity grades: mild, moderate, severe.
Fundus Photography: Number of Participants With Retinal Arteriolar Narrowing as Per Severity
Time frame: Month 12
Number of participants with retinal arteriolar narrowing are reported for severity grades: mild, moderate, severe.
Fundus Photography: Number of Participants With Retinal Vessel Sheathing as Per Severity
Time frame: Month 12
Number of participants with retinal vessel sheathing are reported for severity grades: mild, moderate, severe.
Fundus Photography: Number of Participants With Optic Atrophy/Pallor as Per Severity
Time frame: Month 12
Number of participants with optic atrophy/pallor are reported for severity grades: mild, moderate, severe.
Fundus Photography: Number of Participants With Optic Disc Swelling as Per Severity
Time frame: Month 12
Number of participants with optic disc swelling are reported for severity grades: mild, moderate, severe.
Microperimetry: Retinal Mean Sensitivity at Month 12
Time frame: Month 12
Microperimetry was conducted to assess retinal mean sensitivity within the macula. Retinal mean sensitivity to light was measured in decibels in multiple spots across the central and peripheral retina (entire visual field). Higher numbers (decibels) indicate higher retinal sensitivity.
Microperimetry: Bivariate Contour Ellipse Area 63% at Month 12
Time frame: Month 12
Microperimetry was conducted to assess bivariate contour ellipse area 63%.
Microperimetry: Bivariate Contour Ellipse Area 95% at Month 12
Time frame: Month 12
Microperimetry was conducted to assess bivariate contour ellipse area 95%.
Microperimetry: Fixation Losses (in Percentage) at Month 12
Time frame: Month 12
Microperimetry was conducted to assess fixation losses (in percentage) which samples the optic nerve blind spot for positive responses.
Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
Time frame: Day 0 (surgery) in period 1 up to last follow up visit in period 2 (approximately 2 years)
An AE is any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug/surgical procedure, whether or not related to the investigational product or with the surgical procedure. TEAEs are defined as AEs starting on or after the day of the first surgery.
Number of Participants With Vector Shedding Post-treatment at Month 3
Time frame: Baseline, at Month 3
Tears (for both eyes- oculus dexter [OD] and oculus sinister [OS]), blood, urine and saliva samples were collected and tested using an appropriate assay for evidence of vector shedding. Participants with positive result for vector shredding post treatment are reported.
Number of Participants With Anti-drug Antibodies Post-treatment at Month 12
Time frame: Month 12
Participants with antibodies to the REP-1 transgenic product are reported.
Vital Signs: Change From Baseline in Blood Pressure at Month 12
Time frame: Baseline, Month 12
Change from baseline in Systolic and diastolic blood pressures (BP) (millimeters of mercury [mmHg]) were reported.
Vital Signs: Change From Baseline in Pulse Rate at Month 12
Time frame: Baseline, Month 12
Change from baseline in pulse rate (beats per minute) were reported.

14 secondary outcomes

Change From Baseline in BCVA as Measured by the ETDRS Chart
Time frame: Baseline, Month 12
AF: Change From Baseline in Total Area of Preserved Autofluorescence at Month 12
Time frame: Baseline, Month 12
AF: Change From Baseline in Square Root of Total Area of Preserved AF at Month 12
Time frame: Baseline, Month 12
AF: Change From Baseline in Distance From Foveal Center to Nearest Border of Preserved AF at Month 12
Time frame: Baseline, Month 12
SD-OCT: Change From Baseline in Foveal Subfield Thickness at Month 12
Time frame: Baseline, Month 12
SD-OCT: Change From Baseline in Total Macular Volume at Month 12
Time frame: Baseline, Month 12
SD-OCT: Change From Baseline in the Central Horizontal Ellipsoid Width at Month 12
Time frame: Baseline, Month 12
SD-OCT: Change From Baseline in Central Ellipsoid Area at Month 12
Time frame: Baseline, Month 12
SD-OCT: Change From Baseline in Square Root of Central Ellipsoid Area at Month 12
Time frame: Baseline, Month 12
SD-OCT: Change From Baseline in the Choroidal Thickness at Foveal Center at Month 12
Time frame: Baseline, Month 12
Microperimetry: Change From Baseline in Retinal Mean Sensitivity at Month 12
Time frame: Baseline, Month 12
Microperimetry: Change From Baseline in Bivariate Contour Ellipse Area 63% at Month 12
Time frame: Baseline, Month 12
Microperimetry: Change From Baseline in the Bivariate Contour Ellipse Area 95% at Month 12
Time frame: Baseline, Month 12
Microperimetry: Change From Baseline in Fixation Losses (in Percentage) at Month 12
Time frame: Baseline, Month 12

Results and safety

Results posted to the registry on 18 Sep 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment Period 1: BIIB111	60	50
Treatment Period 2: BIIB111	0	0

Primary outcome: Mean Best-Corrected Visual Acuity (BCVA) as Measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) Chart in Letters at Month 12

Time frame: Month 12. Mean (Standard Deviation). Unit: letters

Measure	Treatment Period 1: BIIB111 n = 15	Treatment Period 2: BIIB111 n = 53
Study Eye 1	68.0 (25.18)	76.5 (13.78)
Study Eye 2	82.3 (8.67)	81.2 (10.82)

Primary outcome: Ophthalmic Examination Assessment: Mean Intraocular Pressure (IOP) at Month 12

Time frame: Month 12. Mean (Standard Deviation). Unit: mmHg

Measure	Treatment Period 1: BIIB111 n = 15	Treatment Period 2: BIIB111 n = 52
Study Eye 1	13.5 (3.09)	13.5 (3.12)
Study Eye 2	14.9 (2.50)	13.5 (3.55)

Primary outcome: Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Slit Lamp Examination

Time frame: Baseline, Month 12. Count of participants. Unit: Participants

Measure	Treatment Period 1: BIIB111 n = 60	Treatment Period 2: BIIB111 n = 56
Cornea: Study Eye 1: Baseline	0	0
Cornea: Study Eye 1: Month 12	0	0
Cornea: Study Eye 2: Baseline	0	0
Cornea: Study Eye 2: Month 12	0	0
Conjunctiva: Study Eye 1: Baseline	0	1
Conjunctiva: Study Eye 1: Month 12	0	0
Conjunctiva: Study Eye 2: Baseline	0	0
Conjunctiva: Study Eye 2: Month 12	0	0

Population analysed: All Treated Subjects analysis set included all participants who completed the 'Day of Surgery' visit of Period 1 or 2. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis of specified category at specified timepoint.

Primary outcome: Ophthalmic Examination Assessment: Number of Participants With Clinically Significant Abnormalities in Dilated Ophthalmoscopy

Time frame: Baseline, Month 12. Count of participants. Unit: Participants

Measure	Treatment Period 1: BIIB111 n = 60	Treatment Period 2: BIIB111 n = 56
Vitreous: Study Eye 1: Baseline	0	0
Vitreous: Study Eye 1: Month 12	1	1
Vitreous: Study Eye 2: Baseline	0	0
Vitreous: Study Eye 2: Month 12	0	1
Macula: Study Eye 1: Baseline	57	54
Macula: Study Eye 1: Month 12	15	51
Macula: Study Eye 2: Baseline	58	54
Macula: Study Eye 2: Month 12	15	51

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: Day 0 (surgery) in period 1 up to last follow up visit in period 2 (approximately 2 years). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment Period 1: BIIB111	12 of 60 (20%)	59 of 60 (98.3%)	0 of 60
Treatment Period 2: BIIB111	8 of 56 (14.3%)	53 of 56 (94.6%)	1 of 56

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 38970425MacLaren RE, Audo I, Fischer MD, Huckfeldt RM, Lam BL, Pennesi ME, Sisk R, Gow JA, Li J, Zhu K, Tsang SF. An Open-Label Phase II Study Assessing the Safety of Bilateral, Sequential Administration of Retinal Gene Therapy in Participants with Choroideremia: The GEMINI Study. Hum Gene Ther. 2024 Aug;35(15-16):564-575. doi: 10.1089/hum.2024.017. Epub 2024 Jul 27.
Derived from this study: PubMed 30194931Davis JL. The Blunt End: Surgical Challenges of Gene Therapy for Inherited Retinal Diseases. Am J Ophthalmol. 2018 Dec;196:xxv-xxix. doi: 10.1016/j.ajo.2018.08.038. Epub 2018 Sep 5.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Biogen

6 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BIIB111 in people with Choroideremia, run by Biogen at 6 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States, France, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Best-Corrected Visual Acuity (BCVA) as Measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) Chart in Letters at Month 12 (time frame: Month 12). The study lists 28 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03507686, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2024.