ORACLE: A long-term follow-up study to evaluate the safety and durability of GT005 in participants with geographic atrophy, secondary to age-related macular degeneration treated in a Gyroscope-sponsored antecedent study.

GT005, a recombinant adeno-associated viral serotype 2 (AAV2) vector encoding
for human complement factor I, is currently being developed as a potential gene
therapy for GA secondary to AMD.
Current regulatory guidelines [EMA 2009; EMA 2018; FDA 2020] recommend that
participants enrolled in gene therapy clinical trials with viral vectors that
are non-replicating, non-integrating, and have no known potential for latency
and re-activation should be followed for approximately 5 years post-treatment.
The aim of this study (GT-ORACLE) is to evaluate the long-term safety and
durability of GT005 for up to 5 years post-treatment.
All participants treated with GT005 in the GT005-02 (EXPLORE, NCT04437368) and
GT005-03 (HORIZON, NCT04566445) study will be invited to enrol in this
long-term, follow-up study.

The overall objectives of the study are to evaluate the long-term safety and
durability of GT005 in participants with GA secondary to AMD who have been
treated in an antecedent study.

This is a prospective, multi-centre, long-term, follow-up study for
participants who received GT005 in an antecedent clinical study (GT005-02 or
GT005-03). No further investigational product will be administered within this
study, and participants will be invited to enter ORACLE upon their completion
of the antecedent interventional study. This study will consist of five study
visits and two phone calls for up to a 5-year period post-GT005 administration.
Following consent, the participants will be asked to attend the following
visits (dates are determined according to the date of GT005 administration in
the antecedent study): Visit 1 (Week 96 post-GT005 administration, should
coincide with the final visit of antecedent study); Visit 2 (Week 126
post-GT005 administration); Visit 3 (Week 156 [3 years] post-GT005
administration); Phone call 1 (Week 182 [3,5 years] post-GT005 administration);
Visit 4 (Week 208 [4 years] post-GT005 administration); Phone call 2 (Week 234
[4,5 years] post-GT005 administration); and Visit 5 (Week 260 [5 years]
post-GT005 administration).
At each visit, an attempt should be made to perform all ophthalmic procedures
in both eyes. Each eye should be tested separately. If the participant is
unable to complete a procedure for any reason, this should be documented in the
source notes.
Participants who develop cataracts during the study may undergo cataract
surgery if deemed clinically necessary. If cataract surgery is performed, it
should be carried out at least 4 weeks before the next study visit.
In the case of unscheduled ocular surgery (e.g., cataract), a vitreous and/or
aqueous sample may be taken during surgery. Each participant must provide a
separate study consent for vitreous or aqueous samples to be taken, if the
occasion arises.
The end of the study will be defined as the last visit by the last participant.
All participants will be followed up, post-study, as per normal standard of
care for their disease and at the discretion of the Investigator.

Not applicable

The risk/benefit assessment for this long-term follow-up study is considered
favourable, as no significant risks have been identified with study
participation. Moreover, future patients are anticipated to benefit from the
evaluation of the long-term durability and safety evaluation of GT005 treatment
in participants with GA secondary to AMD.