A Phase 1b Dose Escalation Evaluation of Safety and Tolerability and a Phase 2 Proof of Concept Investigation of Efficacy and Safety of ASP7317 for Atrophy Secondary to Age-related Macular Degeneration

General Information

Summary The purpose of this study during the Dose Escalation stage is to assess the safety and tolerability of 3 ascending doses of ASP7317 in participants with age-related macular degeneration (AMD), of which one dose will be selected for evaluation of efficacy and safety during the Proof of Concept (PoC) stage of the study. The primary purpose of the study during the PoC stage is to assess the safety, tolerability and superiority of ASP7317 at low cells/dose and the selected dose compared to untreated control and ASP7317 low cells/dose versus the selected dose in best corrected visual acuity (BCVA). This study will also assess safety by incidence of graft failure or rejection with a 13-week regimen of immunosuppression therapy. Efficacy will also be assessed by the differences among ASP7317 at low cells/dose, ASP7317 at the selected dose and the untreated control group in other functional and structural parameters and patient reported outcomes during the PoC stage. During the Extension stage this study will assess the safety and tolerability of ASP7317 at the most efficacious dose from PoC in participants randomized to the untreated control group.
Description This is a two stage study followed by an extension stage. Stage 1 is a Phase 1b dose escalation evaluation of 3 doses of ASP7317; Stage 2 is Phase 2 Proof of Concept (PoC) investigation and Stage 3 is the extension stage which offers treatment options for participants randomized to the untreated control group in Stage 2. During the dose escalation stage participants will be treated in each of the 3 dose cohorts (low cells/dose; medium cells/dose; high cells/dose). Doses will be administered to the study eye via a subretinal injection. Four weeks after the last participant in each dose cohort is treated, the independent Data Safety Monitoring Board (DSMB) will review data and images. Depending on the safety data there will be a recommendation to continue enrollment in the current cohort, or open enrollment for the next higher dose; stop dose escalation; investigate a lower dose or repeat a dose level. The PoC stage will begin immediately following the decision of the Dose Escalation Committee (DEC) on the selected dose. Participants will be randomized in a 1:1:1 ratio to either the low cells/dose; the selected cells/dose or an untreated control group. Doses will be administered to the study eye via a subretinal injection for the low cells/dose and the selected cells/dose. All participants treated with ASP7317 in the Dose Escalation and PoC stage will receive 13 weeks of immunosuppressive therapy (IMT) starting 1 week prior to day of transplant and continuing for 12 weeks post-transplant. If the primary outcome for PoC is demonstrated for the low cells/dose and the selected cells/dose then participants in the untreated control group who completed the 26 week visit are allowed to cross over to treatment with ASP7317 provided the participants remain suitable for immunosuppression therapy and ASP7317. At the last study visit or time of withdrawal participants receiving ASP7317 will be consented to participate in the safety surveillance period of the study (under a separate protocol 7316-CL-0007), which will continue to monitor the participants for long-term safety via an annual questionnaire.
Clinical trials phase Phases 1/2
Start date (estimated) 2018-07-13
End date (estimated) 2026-10-31
Clinical feature
Label Age-Related Macular Degeneration
Link http://purl.obolibrary.org/obo/NCIT_C84391
Description Age-related loss of vision in the central portion of the retina (macula), secondary to retinal degeneration.

Administrative Information

NCT number NCT03178149
ICTRP weblink http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT03178149
EudraCT number 2016-005099-8
Other study identifiers
Name 7317-CL-0003
Description Other Identifier: Sponsor
Source weblink https://clinicaltrials.gov/ct2/show/NCT03178149
Regulatory body approval
Name Food and Drug Administration (FDA)
Country
United States
Public contact
Email astellas.registration@astellas.com
Public email astellas.registration@astellas.com
Last name Study Director: Global Therapeutic Area Head & Chief Medical Officer, Astellas Institute for Regenerative Medicine
Country
United States
Sponsors Astellas Pharma Inc.

Cell Line

Stem cell lines obtained from

Recruitment

Recruitment Status Recruiting
Estimated number of participants 150