A Randomized, Partially Masked, Controlled, Phase 3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants with nAMD (ASCENT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Abbvie Deutschland GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

7 Jun 2024 → ongoing

Decision date (initial)

2024-02-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AbbVie Inc.

External identifiers

EU CT number

2023-503666-23-00

ClinicalTrials.gov

NCT05407636

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the noninferiority of ABBV-RGX-314 relative to aflibercept in mean change from Baseline BCVA at Week 54

Secondary objectives 5

1. To evaluate the safety and tolerability of ABBV-RGX-314 through Week 54
2. To evaluate the effect of ABBV-RGX-314 relative to aflibercept on BCVA
3. To evaluate the effect of ABBV-RGX-314 relative to aflibercept on CRT as measured by SD-OCT
4. To evaluate the effect of ABBV-RGX-314 relative to aflibercept on CPT as measured by SD OCT
5. To assess the need for supplemental anti-VEGF therapy in participants treated with ABBV-RGX-314

Conditions and MedDRA coding

Neovascular age-related macular degeneration

Regulatory references

Scientific advice from competent authorities

Pharmaceuticals And Medical Devices Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information. To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/ For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1-Age ≥ 50 years and ≤ 89 years
2. 2-An ETDRS BCVA letter score between ≤ 78 and ≥ 40 in the study eye at Week –6 (Screening Visit 1).
3. 3-Diagnosis of CNV secondary to AMD in the study eye. Since nAMD diagnosis, must have received a minimum of 1 intravitreal anti-VEGF injection in the study eye prior to Week –6 (Screening Visit 1) and been responsive.
4. 4-Must be pseudophakic (at least 12 weeks postcataract surgery at Week –2 [Randomization; Screening Visit 3]) in the study eye.
5. 5-Willing and able to provide written, signed informed consent for this study and must not be incarcerated. (Note: adults under legal protection measure [eg, under guardianship/curatorship] and adults unable to express their consent are not able to participate). Investigator's discretion should be applied.
6. 6-Participants must have demonstrated a meaningful response to anti-VEGF therapy at study entry

Exclusion criteria 10

1. 1-CNV or macular edema in the study eye secondary to any causes other than AMD
2. 2-Subfoveal fibrosis or atrophy in the study eye
3. 3-Any condition in the investigator's opinion that could limit VA improvement in the study eye
4. 4-Active or history of retinal detachment or current retinal tear in the study eye
5. 5-Advanced glaucoma or history of secondary glaucoma in the study eye
6. 6-Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months
7. 7-Other clinically significant, active systemic or localized infections at any screening visit that may compromise the participant's safety or interpretation of results such as: mycobacterial, fungal, or viral infections (eg, HIV, hepatitis B or C, SARS-CoV-2 2019 [COVID-19], Epstein-Barr virus, syphilis, HSV, varicella-zoster virus, CMV).
8. 8-History of intraocular surgery in the study eye within 12 weeks prior to Week –2 (Randomization; Screening Visit 3). Yttrium aluminum garnet capsulotomy is permitted if performed > 10 weeks prior to the Week –6 (Screening Visit 1).
9. 9-History of intravitreal therapy in the study eye, such as intravitreal steroid injection or investigational product, other than anti-VEGF therapy, in the 6 months prior to Screening Visit 1.
10. 10-Prior treatment with gene therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean change from baseline in BCVA to Week 54 based on the ETDRS score (noninferiority to the active control).

Secondary endpoints 22

1. 1. Incidences of ocular and overall AEs over 54 weeks
2. 2. Proportion of participants with BCVA of 40 letters (20/160 approximate Snellen equivalent) or worse at Week 54
3. 3. Proportion of participants with BCVA of 84 letters (20/20 approximate Snellen equivalent) or better at Week 54
4. 4. Proportion of participants (1) gaining ≥ 15, ≥ 10, ≥ 5, or ≥ 0 letters; (2) losing ≥ 15, ≥ 10, ≥ 5, or > 0 letters; (3) maintaining vision (not losing ≥ 15 letters) compared with Baseline as per BCVA at Week 54
5. 5. Mean change from Baseline in BCVA to Week 54 for participants who received ≤ 3 supplemental anti-VEGF injections, ≤ 2 supplemental anti-VEGF injections, ≤ 1 supplemental anti-VEGF injection, or 0 supplemental anti-VEGF injections (ABBV RGX 314 randomized participants)
6. 6. Mean change from Week 54 to Week 108 in BCVA (control arm participants who cross over to ABBV-RGX-314)
7. 7. Mean change from Baseline in CRT as measured by SD-OCT to Week 54
8. 8. Mean change from Week 54 to Week 108 in CRT, as measured by SD-OCT (control arm participants who cross over to ABBV-RGX-314)
9. 9. Mean change from Baseline in CPT as measured by SD-OCT to Week 54
10. 10. Mean change from Week 54 to Week 108 in CPT, as measured by SD-OCT (control arm participants who cross over to ABBV RGX 314)
11. 11. Mean number of supplemental anti-VEGF injections from Baseline through Week 54 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 108 (control arm participants who cross over to ABBV-RGX-314)
12. 12. Proportion of participants with 0, 1, 2, and 3 supplemental injections through Week 54 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 108 (control arm participants who cross over to ABBV-RGX-314)
13. 13. Proportion of participants with ≤ 1, ≤ 2, and ≤ 3 supplemental injections through Week 54 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 108 (control arm participants who cross over to ABBV-RGX-314)
14. 14. In the subset of participants who were given supplemental anti-VEGF injections, proportion of participants that received 1 or 2 injections through Week 54 (ABBV-RGX-314 randomized participants) and from Week 54 through Week 108 (control arm participants who cross over to ABBV-RGX-314)
15. 15. Proportion of participants with a reduction of ≥ 50% in anti-VEGF injection annualized rate through Week 54 compared with the prior year (ABBV-RGX-314 randomized participants)
16. 16. Proportion of participants with a reduction of ≥ 75% in anti-VEGF injection annualized rate through Week 54 compared with the prior year (ABBV-RGX-314 randomized participants)
17. 17. Percent reduction in anti-VEGF injection annualized rate through Week 54 compared with the prior year (ABBV-RGX-314 randomized participants)
18. 18. Supplemental anti-VEGF injection annualized rate through Week 54 (ABBV-RGX-314 randomized participants)
19. 19. Percent reduction in anti-VEGF injection annualized rate after Week 58 through Week 108 relative to the year prior to the study (control arm participants who cross over to ABBV-RGX-314)
20. 20. Supplemental anti-VEGF injection annualized rate after Week 58 through Week 108 (control arm participants who cross over to ABBV-RGX-314)
21. 21. Time to first supplemental anti-VEGF injection after the Week 2 injection (ABBV-RGX-314 randomized participants)
22. 22. Time to first supplemental anti-VEGF injection after the Week 58 injection (control arm participants who cross over to ABBV RGX 314)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Abbvie Deutschland GmbH & Co. KG

Sponsor organisation

Abbvie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

Abbvie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Public contact point

Organisation

Abbvie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Third parties 16

Locations

5 EU/EEA countries · 39 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 55 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications