A Study of the Safety and Tolerability of ASP7317 in Senior Adults Who Are Losing Their Clear, Sharp Central Vision Due to Geographic Atrophy Secondary to Dry Age-related Macular Degeneration

NCT03178149 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 7317-CL-0003
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 19

Brief Summary

Age-related macular degeneration (AMD) is an eye disease which causes people to lose their sharp central vision over time. Aging damages the macula, which is in the middle of the retina - the light-sensitive part at the back of the eye. There are 2 types of AMD - wet AMD and dry AMD. The advanced stage of dry AMD causes vision loss. This is known as geographic atrophy. AMD makes everyday tasks like reading or driving difficult. ASP7317 is a potential new treatment for people with AMD. ASP7317 are human stem cells which have changed into cells found in the retina. ASP7317 is injected under the macula. It is hoped that ASP7317 will replace some of the damaged cells in the macula and improve vision for people with dry AMD. Before ASP7317 is available as a treatment, the researchers need to check its safety and how well it is tolerated. They will also check for signs of improved vision. People taking part in this study will be older people who have geographic atrophy caused by dry AMD. This is an open-label study. This means that people in this study and clinic staff will know that people will receive ASP7317. There will be 3 doses of ASP7317. These are low, medium and high numbers of cells. ASP7317 will be injected under the macula after the person is given either a local or a general anesthetic. To prevent the body from rejecting the cells, people will take tablets of tacrolimus a few days before receiving ASP7317 for up to a few weeks afterwards. Other medicines will be taken during this time to stop infections. There will be 2 groups in the study. Group 1 will be people with severe vision loss and Group 2 will be people with moderate vision loss. There will be different small groups of people within Group 1 and Group 2, with each small group receiving 1 of the 3 doses of ASP7317. Different small groups of people within Group 1 and Group 2 will receive lower to higher doses of ASP7317. Each small group will only receive 1 dose. Group 1 will start treatment first. At each dose, a medical expert panel will check the results of the first person in the group to decide if the rest of the group will receive the same dose. Then, the panel will decide if more people may receive the same dose or if the next group may receive the next highest dose. The panel will use the results from the lower dose of Group 1 to decide when Group 2 starts treatment (also at the lower dose). The panel will also use the results of the middle and higher doses in Group 1 to decide when and how many people in Group 2 can receive these doses. During the study, people will visit the clinic several times for up to 12 months (1 year). During all visits, the study doctors will check for any medical problems after receiving ASP7317. Vital signs will be checked a few days before treatment with ASP7317 and up to about a month afterwards. Vital signs include blood pressure, pulse, and temperature. At some visits, the study doctors will also take blood samples for blood tests. At most visits, people will have eye tests and have different images, scans, and measurements taken. This could be for the affected eye or both eyes, depending on the test. People can visit the clinic extra times, if needed.

Conditions

Age-Related Macular Degeneration

Keywords

Geographic Atrophy; Age-related Macular Degeneration; ASP7317

Outcome Measures

Primary Outcomes (5)

• Safety as assessed by incidence, frequency and severity of treatment emergent adverse events (TEAES)

  Adverse events (AEs) will be coded using Medical Dictionary for Regulatory Activities (MedDRA). An Adverse Event is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of ASP7317, the adjunct study medications and the study procedures, whether or not considered related to ASP7317, the adjunct study medications and the study procedures. A Treatment Emergent Adverse Event (TEAE) is defined as an AE beginning or worsening in severity after starting administration of the adjunct study medication.

  Up to 52 Weeks

• Safety as assessed by incidence, frequency and severity of Serious Adverse Events (SAEs)

  An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in congenital anomaly or birth defect or other medically important events.

  Up to 52 Weeks

• Safety assessed by Adverse Events (AEs) of special interest

  AEs of special interest include: ectopic or proliferative cell growth (retinal pigment epithelial/epithelium (RPE) or non-RPE) with adverse clinical consequence; any new diagnosis of an immune-mediated disorder; any new cancer, irrespective of prior history; unexpected, clinically significant AEs possibly related to the cell transplant procedure; immunosuppressive therapy (IMT) or ASP7317 (e.g., graft failure or rejection).

  Up to 52 Weeks

• Number of participants with cellular graft failure or rejection

  Evidence of cellular graft failure or rejection will be assessed by best corrected visual acuity (BCVA), slit lamp examination, dilated indirect ophthalmoscopy, fundus photographs, spectral domain-optical coherence tomography (SD-OCT) and fluorescein angiography (FA), when performed.

  Up to 52 Weeks

• Incidence of cellular graft failure or rejection

  Evidence of cellular graft failure or rejection will be assessed by best corrected visual acuity (BCVA), slit lamp examination, dilated indirect ophthalmoscopy, fundus photographs, spectral domain-optical coherence tomography (SD-OCT) and fluorescein angiography (FA), when performed.

  Up to 52 Weeks

Secondary Outcomes (12)

• Mean change from baseline in area of Geographic Atrophy (GA) (mm^2) in study eye and fellow eye

  Baseline, Weeks 26 and 52/End of Study (EOS)

• Mean percent change from baseline in area of Geographic Atrophy (GA) (mm^2) in study eye and fellow eye

  Baseline, Weeks 26 and 52/End of Study (EOS)

• Mean change from baseline in the square root transformation of Geographic Atrophy (GA) area in study eye and fellow eye

  Baseline, Weeks 26 and 52/End of Study (EOS)

• Mean change from baseline in best corrected visual acuity (BCVA) score in study eye and fellow eye

  Baseline, Weeks 1, 4, 6, 8, 12, 16, 26 and 52/End of Study (EOS)

• Mean change from baseline in mean sensitivity

  Baseline, Weeks 4, 12, 26 and 52/End of Study (EOS)

Study Arms (2)

ASP7317 Dose Escalation/ Expansion (Group 1: Severe Vision Loss)

EXPERIMENTAL

Successive cohorts of participants (3 participants each) will be given escalating doses (cohort 1: low cells/dose; cohort 2: medium cells/dose; cohort 3: high cells/dose). Optional Expansion cohorts 3b will be opened after cohort 3 has been filled and 2b will be opened only if necessary. Dose levels for the expansion cohort will align with dose levels in escalation cohorts. Sentinel dosing will be required for each dose level. After the first participant in each dose cohort in Group 1 is dosed and followed for 4 weeks, the Independent Data Monitoring Committee (IDMC) will review the 4-week safety data and recommend if the second and third participants in Group 1 dose cohort may be treated. The IDMC recommendation to progress to the next dosing cohort will be based on 4-week follow-up safety review of the second and third participants in the preceding dose cohort. Participants will receive tacrolimus and other medicines to stop infection.

Drug: ASP7317; Drug: tacrolimus; Drug: trimethoprim-sulfamethoxazole; Drug: Acyclovir; Drug: Nystatin

ASP7317 Dose Escalation/ Expansion (Group 2: Moderate Vision Loss)

EXPERIMENTAL

Successive cohorts of participants (3 participants each) will be given escalating doses (cohort 4: low cells/dose; cohort 5: medium cells/dose; cohort 6: high cells/dose). Optional Expansion cohorts 5b and 6b will be opened after cohorts 5 and 6 have been filled. Dose levels for the expansion cohorts will align with dose levels in escalation cohorts. Cohort 4 (low cells/dose) dosing may begin after the IDMC recommendation to begin dosing in Group 1 cohort 2 (medium cells/dose). Cohort 5 (medium cells/dose) dosing may begin after IDMC review of the 4- week safety data of the first participant in Group 1 cohort 2 (medium cells/dose). Cohort 6 (high cells/dose) dosing may begin after IDMC review of 4-week safety data of the first participant in Group 1 cohort 3 (high cells/dose). Dosing in cohort 5 and 6 can only begin after the IDMC review and the completion of the preceding cohort. Participants will receive tacrolimus and other medicines to stop infection.

Drug: ASP7317; Drug: tacrolimus; Drug: trimethoprim-sulfamethoxazole; Drug: Acyclovir; Drug: Nystatin

Interventions

Acyclovir DRUG

oral

ASP7317 Dose Escalation/ Expansion (Group 1: Severe Vision Loss); ASP7317 Dose Escalation/ Expansion (Group 2: Moderate Vision Loss)

Nystatin DRUG

oral

ASP7317 Dose Escalation/ Expansion (Group 1: Severe Vision Loss); ASP7317 Dose Escalation/ Expansion (Group 2: Moderate Vision Loss)

ASP7317 DRUG

subretinal injection

ASP7317 Dose Escalation/ Expansion (Group 1: Severe Vision Loss); ASP7317 Dose Escalation/ Expansion (Group 2: Moderate Vision Loss)

tacrolimus DRUG

oral

Also known as: FK506, Prograf®

ASP7317 Dose Escalation/ Expansion (Group 1: Severe Vision Loss); ASP7317 Dose Escalation/ Expansion (Group 2: Moderate Vision Loss)

trimethoprim-sulfamethoxazole DRUG

oral

Also known as: TMP/SMX

ASP7317 Dose Escalation/ Expansion (Group 1: Severe Vision Loss); ASP7317 Dose Escalation/ Expansion (Group 2: Moderate Vision Loss)

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be willing to take tacrolimus and willing to discontinue any medications that have a known strong interaction with tacrolimus.
• Participant is able and willing to undertake all scheduled visits and assessments up to the week 52 visit.
• Participant who is taking an antidepressant must be on a stable and effective dosage and must be willing to take it reliably for as long as it is required.
• Participant must be willing and medically suitable to undergo monitored anesthesia care during the vitrectomy and subretinal injection.
• Participant agrees to conform to local and institutional policies regarding active COVID-19 infections.
• Participant agrees not to participate in another interventional study until the 52-week visit has been completed.
• Female participant is not pregnant or at least 1 of the following conditions apply:
• Not a woman of childbearing potential (WOCBP)
• WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 52 weeks after investigational product (IP) administration.
• Female participant must agree not to breastfeed starting at screening and throughout the study period and for 52 weeks after IP administration.
• Female participant must not donate ova starting at first dose of IP and throughout the study period and for 52 weeks after IP administration.
• Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 52 weeks after IP administration.
• Male participant must not donate sperm during the treatment period and for 52 weeks after IP administration.
• Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 52 weeks after IP administration.
• Participant has bilateral AMD and geographic atrophy (GA) secondary to Age-Related Macular Degeneration (AMD) in the study eye. GA is defined as sharply demarcated areas of loss of the retinal pigment epithelial/epithelium (RPE). While having bilateral GA remains the preferred enrollment criterion, it is not a requirement and GA only in the study eye is admissible, as long as both eyes exhibit AMD.

You may not qualify if:

• Participant has a positive tuberculosis (TB) test during the screening period by an interferon gamma release assay (e.g., QuantiFERON) within the 6 months prior to the screening. If a participant has tested negative for TB within the 6 months prior to the screening visit, retesting is not required unless clinically indicated.
• Participant has a history or suspected active infection of toxoplasmosis or presence of elevated immunoglobulin M (IgM) toxoplasmosis titer within 4 weeks of the baseline visit.
• Participant has an active infection (ocular or non-ocular) requiring the prolonged or chronic use of antimicrobial or anti-infective agents.
• Participant has a current malignancy or history of malignancy within the past 5 years, except non-metastatic basal or squamous cell carcinoma or keratoacanthoma or Bowen's disease or carcinoma-in-situ of the cervix that has been successfully treated.
• Participant has a history of a solid organ or bone marrow transplant.
• Participant has any condition that would prohibit the use of systemic immunosuppression with tacrolimus.
• Participant is receiving or has received any immunosuppressive therapy (IMT) (other than topical, inhaled or low dose systemic corticosteroid use not exceeding 7.5 mg of prednisone daily \[or equivalent\]) within 6 weeks or 5 plasma half-lives, whichever is longer, prior to the administration of adjunct study medications.
• Participant has a history of myocardial infarction in previous 12 months and whose disease is either unstable and/or symptomatic (e.g., angina, dyspnea, etc.).
• Participant has electrocardiogram (ECG) results that are clinically significant and could either jeopardize the safety of the participant, impact the participant's ability to comply with study visit schedule or impact the validity of the study results. Participants with a mean Fridericia-corrected QT interval of \> 430 ms (for males) and \> 450 ms (for females) at screening must be cleared by a cardiologist prior to the baseline visit.
• Participant has a study day diastolic blood pressure \> 95 mmHg, at either the screening or baseline visit. Study day blood pressure is defined as the average of the second and third readings at a study visit. If the study day blood pressure exceeds the limits, 1 additional triplicate can be taken.
• Participant has an estimated glomerular filtration rate (eGFR) of \</= 30 mL/min, calculated by the chronic kidney disease epidemiology collaboration (CKD-EPI) equation.
• Participant has an alanine aminotransferase (ALT), aspartate aminotransferase (AST) or gamma- glutamyltransferase (GGT) and total bilirubin (TBL) \>/= 2 times the upper limit of normal (ULN).
• Participant has severe anemia (hemoglobin \< 9 g/dL \[male\] or hemoglobin \< 8 g/dL \[female\]), leucopenia (white blood cell count \< 2500/mm\^3), thrombocytopenia (platelet count \< 80000/mm\^3) or polycythemia (hematocrit \> 54% \[male\] or hematocrit \> 49% \[female\]).
• Participant has a hemoglobin A1c \> 8.5%.
• Participant has a clinically significant coagulopathy (i.e., activated partial thromboplastin time \[aPTT\] \>/= 1.5 times the ULN and/or prothrombin time adjusted for the international normalized ratio \[PT-INR\] \>/=2.0).

Sponsors & Collaborators

• Astellas Institute for Regenerative Medicine: lead

Study Sites (19)

Retinal Consultants of Arizona LTD, Retinal Research Institute

Phoenix, Arizona, 85053, United States

WITHDRAWN

Jules Stein Eye Institute

Los Angeles, California, 90095, United States

RECRUITING

Stanford University Byers Eye Institute

Palo Alto, California, 94303, United States

RECRUITING

Kaiser Permanente Riverside Medical Center

Riverside, California, 92505, United States

RECRUITING

Retina Consultants of Southwest Florida & National Ophthalmic Research Institute

Fort Myers, Florida, 33912, United States

WITHDRAWN

Retina Specialty Institute

Pensacola, Florida, 35203, United States

RECRUITING

Emory University Eye Center

Atlanta, Georgia, 30322, United States

RECRUITING

University Retina and Macula Associates

Oak Forest, Illinois, 60452, United States

RECRUITING

Mass Eye and Ear Infirmary Ophthalmology Clinical Research Office

Boston, Massachusetts, 02114, United States

WITHDRAWN

Ophthalmic Consultants of Boston

Boston, Massachusetts, 02114, United States

RECRUITING

University of Michigan Kellog Eye Center

Ann Arbor, Michigan, 48105, United States

RECRUITING

Deep Blue Retina

Southaven, Mississippi, 38671, United States

RECRUITING

NJ Retina

New Brunswick, New Jersey, 08901, United States

WITHDRAWN

Mid-Atlantic Retina

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Tennessee Retina, PC

Nashville, Tennessee, 37203, United States

WITHDRAWN

Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

RECRUITING

Valley Retina Institute

McAllen, Texas, 78503, United States

COMPLETED

University of Washington

Seattle, Washington, 98104, United States

WITHDRAWN

Spokane Eye Clinical Research

Spokane, Washington, 99204, United States

RECRUITING

Related Links

• Site update

MeSH Terms

Conditions

Macular Degeneration; Geographic Atrophy

Interventions

Tacrolimus; Trimethoprim, Sulfamethoxazole Drug Combination; Acyclovir; Nystatin

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Central Study Contacts

Astellas Institute for Regenerative Medicine

CONTACT

800-888-7704; astellas.registration@astellas.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2017
• First Posted: June 6, 2017
• Study Start: July 13, 2018
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (19)