EXPLORE: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005 (EXPLORE)

• ClinicalTrials.gov Identifier: NCT04437368
• Recruitment Status: Recruiting
• First Posted: June 18, 2020
• Last Update Posted: January 25, 2021
• Sponsor: Gyroscope Therapeutics
• Information provided by (Responsible Party): Gyroscope Therapeutics

Tracking Information

• First Submitted Date: June 3, 2020
• First Posted Date: June 18, 2020
• Last Update Posted Date: January 25, 2021
• Actual Study Start Date: July 14, 2020
• Estimated Primary Completion Date: February 28, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 17, 2020)

Progression of geographic atrophy [ Time Frame: 48 weeks ]

The change from baseline to Week 48 in GA area as measured by fundus fluorescence (FAF)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 17, 2020)

• Evaluation of the safety and tolerability of GT005 [ Time Frame: 48 weeks ]
  Frequency of treatment emergent AEs
• Evaluation of the safety and tolerability of GT005 [ Time Frame: 48 weeks ]
  Change on ophthalmic examination
• Evaluation of the safety and tolerability of GT005 [ Time Frame: 48 weeks ]
  Change in imaging modalities
• Evaluation of the safety and tolerability of GT005 [ Time Frame: 48 weeks ]
  Change in best corrected visual acuity (BCVA)
• Evaluation of the effect of GT005 on retinal anatomical measures [ Time Frame: 48 weeks ]
  Change in retinal microstructures on spectral domain optical coherence tomography (SD-OCT)
• Evaluation of the effect of GT005 on retinal anatomical measures [ Time Frame: 48 weeks ]
  Change in presence of area of nascent GA on SD-OCT
• Evaluation of the effect of GT005 on retinal anatomical measures [ Time Frame: 48 weeks ]
  Change in GA morphology on colour fundus photography (CFP)
• Evaluation of the effect of GT005 on functional measures [ Time Frame: 48 weeks ]
  Macular sensitivity as assessed by mesopic Microperimetry
• Evaluation of the effect of GT005 on functional measures [ Time Frame: 48 weeks ]
  Change in BCVA Score via the early treatment for diabetic retinopathy (ETDRS) chart
• Evaluation of the effect of GT005 on functional measures [ Time Frame: 48 weeks ]
  Change in low luminance difference (LLD) via the ETDRS chart
• Evaluation of the effect of GT005 on visual function [ Time Frame: 48 weeks ]
  Change in reading performance as assessed by Minnesota low-vision reading test (MNRead) Chart
• Evaluation of the effect of GT005 on visual function [ Time Frame: 48 weeks ]
  Change in functional reading independence (FRI) index
• Evaluation of the effect of GT005 on patient-reported outcomes [ Time Frame: 48 weeks ]
  Change in quality of life measured on the Visual Functioning Questionnaire-25 (VFQ-25)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: EXPLORE: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005
• Official Title: EXPLORE: A Phase II, Outcomes Assessor-masked, Multicentre, Randomised Study to Evaluate the Safety and Efficacy of Two Doses of GT005 Administered as a Single Subretinal Injection in Subjects With Geographic Atrophy Secondary to Age-related Macular Degeneration
• Brief Summary: The purpose of this clinical study is to evaluate the safety and efficacy of two doses of GT005 administered as a single subretinal injection in subjects with geographic atrophy secondary to age-related macular degeneration (AMD).

Detailed Description

This is a Phase 2, outcomes assessor-masked, multicentre, randomised study to evaluate the safety and efficacy of two doses of GT005 administered as a single subretinal injection in subjects with GA secondary to AMD.

The trial includes a screening period of up to 8 weeks followed by a 48-week study period.

Subjects will be randomised to two groups; GT005 or the untreated control group.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This is a Phase 2, outcomes assessor-masked multicentre, randomised study to evaluate the safety and efficacy of two doses of GT005 administered as a single subretinal injection in subjects with GA secondary to AMD.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

The overall objectives of the study are to evaluate the safety and efficacy (anatomical and functional visual outcomes) of two doses of GT005 in genetically defined subjects with GA due to AMD.

Primary Purpose: Treatment

• Condition: Dry Age-related Macular Degeneration

Intervention

• Drug: GT005; Dose 1
  The study will test two doses of GT005; Dose 1 and Dose 2.
• Drug: GT005; Dose 2
  The study will test two doses of GT005; Dose 1 and Dose 2.

Study Arms

• Experimental: GT005 Dose 1
  Approximately 25 subjects are planned, with subjects randomised to GT005 Dose 1.
  Intervention: Drug: GT005; Dose 1
• Experimental: GT005 Dose 2
  Approximately 25 subjects are planned, with subjects randomised to GT005 Dose 2.
  Intervention: Drug: GT005; Dose 2
• No Intervention: Untreated control
  Approximately 25 subjects are planned, with subjects randomised to untreated control.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 17, 2020): 75
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 28, 2023
• Estimated Primary Completion Date: February 28, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Able and willing to give written informed consent
2. Age ≥55 years
3. Have a clinical diagnosis of GA secondary to AMD as determined by the Investigator
4. GA lesion(s) within an acceptable size on FAF, in the study eye
5. The GA lesion in the study eye must reside completely within the FAF image
6. Have a BCVA of 34 letters (6/60 and 20/200 Snellen acuity equivalent) or better, using ETDRS charts, in the study eye
7. Serum Complement Factor I level below the lower limit of normal of the selected assay
8. Have a rare genetic variant of the CFI gene, defined as a minor allele frequency of <1%
9. Able to attend all study visits and complete the study procedures
10. Women of child-bearing potential must have a negative pregnancy test within 2 weeks prior to randomisation

Exclusion Criteria:

1. Have evidence or history of CNV in either eye
2. Presence of moderate/severe or worse non-proliferative diabetic retinopathy in the study eye
3. Have history of vitrectomy, sub-macular surgery, or macular photocoagulation in the study eye
4. Have clinically significant cataract that may require surgery during the study period in the study eye
5. Presence of moderate to severe glaucomatous optic neuropathy in the study eye, uncontrolled intraocular pressure (IOP), use of two or more topical agents to control IOP, or a history of glaucoma-filtering surgery
6. Axial myopia of greater than -8 diopters in the study eye
7. Have any other significant ocular or non-ocular medical or psychiatric condition which, in the opinion of the Investigator, may either put the subject at risk or may influence the results of the study
8. Have a contraindication to oral prednisolone/prednisone
9. Have received any investigational product for the treatment of GA within the past 6 months, or 5 half-lives (whichever is longer) other than nutritional supplements such as the AREDS formula
10. Have received a gene or cell therapy at any time
11. Are unwilling to use two forms of contraception (one of which being a barrier method) for 90 days post-dosing, if relevant
12. Have a history or presence of cutaneous squamous cell carcinoma

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 55 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Gyroscope Therapeutics; +441438532142; clinicaltrials@gyroscopetx.com

• Listed Location Countries: Germany, United Kingdom, United States

Administrative Information

• NCT Number: NCT04437368
• Other Study ID Numbers: GT005-02
• 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: Not Provided
• Responsible Party: Gyroscope Therapeutics
• Study Sponsor: Gyroscope Therapeutics
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Gyroscope Therapeutics
• Verification Date: January 2021