Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03178149
Recruitment Status : Recruiting
First Posted : June 6, 2017
Last Update Posted : June 28, 2019
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Institute for Regenerative Medicine )

Tracking Information
First Submitted Date  ICMJE May 24, 2017
First Posted Date  ICMJE June 6, 2017
Last Update Posted Date June 28, 2019
Actual Study Start Date  ICMJE July 13, 2018
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 20, 2019)
  • PoC only: Change from baseline in BCVA score, measured by ETDRS method at week 26 [ Time Frame: Baseline and Week 26 ]
    Best corrected visual acuity (BCVA) will be measured by an assessor certified to use the early treatment of diabetic retinopathy study (ETDRS) method. The BCVA score (in letter units) will be reported.
  • Safety as assessed by Incidence, frequency and severity of adverse events (AEs) [ Time Frame: Up to 60 Months ]
    Adverse events (AEs) will be coded using Medical Dictionary for Regulatory Activities (MedDRA). Adverse event collection will begin upon the participant signing the informed consent.
  • Safety as assessed by Incidence, frequency and severity of Serious adverse events (SAEs) [ Time Frame: Up to 60 Months ]
    An AE is considered "serious" if, in the view of either the investigator or sponsor, it results in any of the following outcomes: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect; requires inpatient hospitalization (except for planned procedures as allowed per study) or leads to prolongation of hospitalization (hospitalization for treatment/observation/examination caused by AE is to be considered as serious); or other medically important events.
  • Safety as assessed by Incidence, frequency and severity of advanced therapy investigational medicinal product (ATIMP) events [ Time Frame: Up to 60 Months ]
    ATIMP events which may represent a significant hazard to the trial's participant population, and thus require expedited reporting, including but not limited to the following example ATIMPs: ectopic or proliferative cell growth (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, IMT or ASP7317 (e.g., graft failure or rejection).
  • Number of Participants with graft failure or rejection [ Time Frame: Up to 60 Months ]
    Evidence of graft failure or rejection will be assessed by BCVA, slit lamp examination, dilated indirect ophthalmoscopy, fundus photographs, spectral domain-optical coherence tomography (SD-OCT) and fluorescein angiography (FA), when performed.
  • Incidence of graft failure or rejection [ Time Frame: Up to 60 Months ]
    Evidence of graft failure or rejection will be assessed by BCVA, slit lamp examination, dilated indirect ophthalmoscopy, fundus photographs, spectral domain-optical coherence tomography (SD-OCT) and fluorescein angiography (FA), when performed.
  • Time of onset of ASP7317 to graft failure or rejection [ Time Frame: Up to 60 Months ]
    Immediate notification (within 24 hours of becoming aware) to the sponsor is required for any evidence of graft failure or rejection. AEs which are assessed as being evidence of graft failure or rejection will be summarized in additional AE tables, including time to onset relative to the start of adjunct study medication.
  • Number of clinically significant objective test results in laboratory tests [ Time Frame: Up to 26 Weeks ]
    An abnormality identified during a medical test will be defined as an AE only if the abnormality meets 1 of the following criteria: induces clinical signs or symptoms; requires active intervention; requires interruption or discontinuation of adjunct study medications; age-related eye disease studies (AREDS) lens grade increase from baseline by ≥ 1 grade; the abnormality or test value is clinically significant; visual acuity loss of ≥ 10 letters due to graft failure or rejection.
  • Number of clinically significant objective test results in blood pressure [ Time Frame: Up to 12 Weeks ]
    Clinically significant changes in blood pressure will be reported as moderate or severe.
  • Number of clinically significant objective test results in anterior chamber (AC) cells grade [ Time Frame: Up to 26 Weeks ]
    Clinically significant changes in AC cells grade will be reported with a grade ranging from 0 to 4+ (0 = good and 4+ = not good), on a scale from <1 to >50, with cells in field as the indicator (0 = <1 cells in the field and 4+ = >50 cells in the field).
  • Number of clinically significant objective test results in AC flare grade [ Time Frame: Up to 26 Weeks ]
    Clinically significant changes in flare grade will be reported with a grade ranging from 0 to 4+ and defined as follows: none (grade 0), faint (grade 1), moderate (iris and lens details clear, grade 2), marked (iris and lens details hazy, grade 3), and intense (fibrin or plastic aqueous, grade 4).
  • Number of clinically significant objective test results in vitreous haze grade [ Time Frame: Up to 26 Weeks ]
    Clinically significant changes in vitreous haze grade will be reported with a grade ranging from 0 to 4+ and defined as follows: clear (grade 0), opacities without obstruction of retinal details (grade 1), few opacities resulting in the mild burning of posterior details of optic nerve and retinal vessels (grade 2), optic nerve head and retinal vessels significantly blurred but still visible (grade 3), dense opacity obscuring optic nerve head (grade 4).
  • Number of clinically significant objective test results in intraocular pressure (IOP) in each eye [ Time Frame: Up to 60 Months ]
    Intraocular pressure in both eyes will be measured by tonometry. Intraocular pressure should be measured after biomicroscopic examination and before pupil dilation approximately the same time of day, when possible.
Original Primary Outcome Measures  ICMJE
 (submitted: June 5, 2017)
  • PoC only: Change from baseline in BCVA, measured by ETDRS method, average of assessments from weeks 4 to 26 [ Time Frame: Baseline and up to Week 26 ]
    Best corrected visual acuity (BCVA) will be measured by an assessor certified to use the early treatment of diabetic retinopathy study (ETDRS) method. Total number of letters read correctly will be reported.
  • Safety as assessed by Incidence, frequency and severity of adverse events (AEs) [ Time Frame: Up to 60 Months ]
    Adverse events (AEs) will be coded using Medical Dictionary for Regulatory Activities (MedDRA). Adverse event collection will begin upon the participant signing the informed consent.
  • Number of Participants with graft failure or rejection [ Time Frame: Up to 60 Months ]
    Evidence of graft failure or rejection will be assessed by BCVA, slit lamp examination, dilated indirect ophthalmoscopy, fundus photographs, spectral domain-optical coherence tomography (SD-OCT) and fluorescein angiography (FA), when performed.
  • Number of Participants with clinically significant changes in laboratory tests [ Time Frame: Up to 26 Weeks ]
    An abnormality identified during a medical test will be defined as an AE only if the abnormality meets 1 of the following criteria: induces clinical signs or symptoms; requires active intervention; requires interruption or discontinuation of adjunct study medications; age-related eye disease studies (AREDS) lens grade increase from baseline by ≥ 1 grade; the abnormality or test value is clinically significant; visual acuity loss of ≥ 10 letters due to graft failure or rejection.
  • Number of Participants with clinically significant changes in blood pressure [ Time Frame: Up to 12 Weeks ]
    Clinically significant changes in blood pressure will be reported as moderate or severe.
  • Number of Participants with clinically significant changes in intraocular pressure (IOP) in each eye [ Time Frame: Up to 60 Months ]
    Intraocular pressure in both eyes will be measured by tonometry. Intraocular pressure should be measured after biomicroscopic examination and before pupil dilation approximately the same time of day, when possible.
Change History Complete list of historical versions of study NCT03178149 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2019)
  • PoC only: Change from baseline in BCVA score, average of assessments from weeks 4 to 26 [ Time Frame: Baseline and up to Week 26 ]
    BCVA will be measured by an assessor certified to use the ETDRS method. The BCVA score (in letter units) will be reported.
  • PoC only: Participant response, defined as a confirmed ≥ 10-letter (0.2 logMAR) improvement in BCVA, at week 26 [ Time Frame: Week 26 ]
    BCVA will be measured by an assessor certified to use the ETDRS method.
  • PoC only: Change from baseline in mean retinal sensitivity of all test points in the index quadrant at week 26 [ Time Frame: Baseline and Week 26 ]
    The index quadrant is defined as the macular quadrant (superior, temporal, inferior or nasal) where ASP7317 is injected or, for the untreated control group, this is the macular quadrant recommended for ASP7317 injection by the subject selection committee (SSC).
  • PoC only: Change from baseline in (square root) area of definite decreased autofluorescence (DDAF) in the index quadrant at week 26 [ Time Frame: Baseline and Week 26 ]
    DDAF will be assessed by Fundus Autofluorescence Photography (FAF). The image reading center will review the FAF images for area of DDAF and pattern of hyper autofluorescence around the DDAF.
  • Change from baseline in the Functional Reading Independence Index (FRII) at week 26 [ Time Frame: Baseline and Week 26 ]
    The FRII is a 7-item questionnaire that evaluates the effect of geographic atrophy on a patient's ability to independently perform reading activities.
  • Change from baseline in the Impact of Vision Impairment - Very Low Vision questionnaire (IVI-VLV) at week 26 [ Time Frame: Baseline and Week 26 ]
    The IVI-VLV questionnaire (28 questions) will be used to assess activities of daily living, mobility, safety and emotional well-being. This questionnaire measures perceived restriction of participation associated with daily living activities.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2017)
  • PoC only: Change from baseline in BCVA at week 26 [ Time Frame: Baseline and Week 26 ]
    BCVA will be measured by an assessor certified to use the ETDRS method. Total number of letters read correctly will be reported.
  • PoC only: Proportion of participants with confirmed ≥ 15 letter improvement in BCVA at week 26 [ Time Frame: Baseline and Week 26 ]
    BCVA will be measured by an assessor certified to use the ETDRS method.
  • PoC only: Change from baseline in mean retinal sensitivity of the perilesional points by microperimetry at week 26 [ Time Frame: Baseline and Week 26 ]
    Microperimetry will be performed at all sites using a macular integrity assessment (MAIA) microperimeter.
  • PoC only: Change from baseline in area of definite decreased autofluorescence (DDAF) at week 26 [ Time Frame: Baseline and Week 26 ]
    DDAF will be assessed by Fundus Autofluorescence Photography (FAF). The image reading center will review the FAF images for area of DDAF and pattern of hyper autofluorescence around the DDAF.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE A Staged Study Incorporating a Phase 1b, Multicenter, Unmasked, Dose Escalation Evaluation of Safety and Tolerability and a Phase 2, Multicenter, Unmasked, Randomized, Parallel Group, Controlled, Proof of Concept Investigation of Efficacy and Safety of ASP7317 for Atrophy Secondary to Age-related Macular Degeneration
Brief 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.

Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Age-Related Macular Degeneration
Intervention  ICMJE
  • Drug: ASP7317
    subretinal injection
  • Other: Placebo
    no treatment
  • Drug: tacrolimus
    oral
    Other Names:
    • FK506
    • Prograf®
  • Drug: mycophenolate mofetil (MMF)
    oral
Study Arms  ICMJE
  • Experimental: ASP7317 Dose Escalation
    Successive cohorts of participants (3 participants/ 3 cohort) will be treated in each escalating dose cohort (low cells/dose; medium cells/dose; high cells/dose). All participants in the low cells/dose and medium cells/dose cohorts may be treated simultaneously. The high cells/dose cohort will require sentinel dosing. After the first participant is dosed with high cells/dose and followed for 6 weeks the independent Data Safety Monitoring Board (DSMB) will review the safety data and images and recommend if the second and third participants may be treated with high cells/dose. One of the 3 doses will be selected for evaluation of efficacy and safety during the Proof of Concept (PoC) stage of the study. All participants will receive 13 weeks of immunosuppressive therapy (IMT) starting 1 week prior to day of transplant and continuing for 12 weeks posttransplant.
    Interventions:
    • Drug: ASP7317
    • Drug: tacrolimus
    • Drug: mycophenolate mofetil (MMF)
  • Experimental: ASP7317 PoC Low Dose
    Low cells/ dose will be administered to the study eye via a subretinal injection. All participants randomized to receive treatment with ASP7317 will receive 13 weeks of IMT starting 1 week prior to day of transplant and continuing for 12 weeks posttransplant.
    Interventions:
    • Drug: ASP7317
    • Drug: tacrolimus
    • Drug: mycophenolate mofetil (MMF)
  • Experimental: ASP7317 PoC Selected Dose from Dose Escalation
    Selected cells/ dose will be administered to the study eye via a subretinal injection. All participants randomized to receive treatment with ASP7317 will receive 13 weeks of IMT starting 1 week prior to day of transplant and continuing for 12 weeks posttransplant.
    Interventions:
    • Drug: ASP7317
    • Drug: tacrolimus
    • Drug: mycophenolate mofetil (MMF)
  • Placebo Comparator: Placebo untreated group
    Untreated participants with age-related macular degeneration (AMD)
    Intervention: Other: Placebo
  • Experimental: ASP7317 Low Dose or Selected Dose Extension
    If the primary endpoint for PoC is demonstrated for the selected cells/dose or low cells/dose of ASP7317, participants in the untreated control group, who completed the 26-week visit, will be allowed to cross over to treatment with ASP7317 in an extension stage of the protocol, provided the participant continues to meet eligibility criteria and are suitable for receiving IMT.
    Interventions:
    • Drug: ASP7317
    • Drug: tacrolimus
    • Drug: mycophenolate mofetil (MMF)
  • Experimental: ASP7317 Safety Surveillance
    Participants consented to participate in the safety surveillance will be monitored for the participants long term safety via an annual health questionnaire.
    Interventions:
    • Drug: ASP7317
    • Drug: tacrolimus
    • Drug: mycophenolate mofetil (MMF)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 5, 2017)
150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2026
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

General Inclusion Criteria:

  • Subject must be willing to take immunosuppressive therapy (IMT) and willing to discontinue any medication that has a known strong interaction with Prograf or MMF.
  • Subject should be in sufficiently good mental and physical health to reasonably be expected to complete the study to the week 26 visit.
  • Subject must have a score of ≤ 9 on the patient health questionnaire depression scale (PHQ-9) at the screening visit (criterion not applicable for subjects in dose escalation stage).
  • Subject 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.
  • Subject must be willing and medically suitable to undergo monitored anesthesia care during the transplant.
  • Subject is medically suitable to undergo vitrectomy and subretinal injection.
  • Subject agrees not to participate in another interventional study until the 26-week visit has been completed.
  • Pregnancy, breastfeeding, effective forms of birth control and ova/sperm donation criteria are specified in the clinical protocol and will be discussed with potential study subjects during the informed consent process.

Ocular Inclusion Criteria:

  • Subject has atrophy secondary to AMD in the study eye.
  • Subject has the border of the area of definite decreased autofluorescence (DDAF) in the study eye, within the vascular arcades (criterion not applicable for subjects in dose escalation stage).
  • Subject has a best corrected visual acuity (BCVA) score ≤37 early treatment diabetic retinopathy study (ETDRS) letters, in the study eye, at the second assessment during the screening visit between 4 and 23 ETDRS letters. In the dose escalation stage for the first dose cohort only, the study eye must be between light perception and ≤ 23 ETDRS letters at the second assessment during the screening visit.
  • Subject has stable BCVA, in the study eye, to ensure stability of the visual acuity measures for study analyses (criterion not applicable for subjects in dose escalation stage).
  • Subject has spectral domain-optical coherence tomography (SD-OCT) scans obtained of the study eye at the screening visit of suitable quality for grading retinal microstructures.
  • Subject, at the screening visit, must have in the study eye an area with reduced retinal function and evidence of structural retinal preservation between the border of the area of atrophy and the vascular arcades, as determined by the subject selection committee (SSC) (criterion not applicable for subjects in dose escalation stage).
  • Subject is recommended by the SSC for trial participation.

Inclusion Criteria for Extension Stage 3:

  • Subject was previously enrolled as an untreated control subject in the PoC stage and completed the 26-week visit.
  • Subject is suitable to receive IMT and ASP7317 as determined by the SSC.

Exclusion Criteria:

- Subject is an employee of Astellas.

Ophthalmic Disease/Conditions:

The following conditions are exclusionary if present in the study eye, unless otherwise specified.

  • Subject has foveal sparing as determined by either of the following methods (criterion not applicable for subjects in dose escalation stage):

    • Any of the 9 loci in central square of the macula test grid with ≥ 0 dB sensitivity based on microperimetry testing at the prescreening or screening visit assessments.
    • Presence of potentially viable photoreceptors, as evidenced by presence of ellipsoid zone (EZ), ≤ 250.
  • Subject has evidence of prior or active choroidal neovascularization (CNV). Evidence of CNV will be assessed by the image reading center through review of the screening fundus photographs, fluorescein angiography (FA) and SD-OCT images. Evidence of CNV seen on 1 or more imaging modality is exclusionary.
  • Subject has macular atrophy due to causes other than AMD.
  • Subject has pathologic myopia defined as a spherical equivalent of > 8.00 diopters or axial length > 28 mm at the prescreening or screening visit, or myopic macular degeneration.
  • Subject has a contraindication to pupil dilation.
  • Subject has any other current sight-threatening ocular disease.
  • Subject has presence of a posterior staphyloma.
  • Subject has a current or prior history of optic neuropathy.
  • Subject has presence of a macular hole.
  • Subject has presence of macular schisis.
  • Subject has a current or prior history of retinal dystrophy, retinitis pigmentosa, chorioretinitis, central serous choroidopathy, diabetic retinopathy, diabetic macular edema, vasoocclusive disease or other retinal vascular disease (e.g., compromised blood-retinal barrier) or retinal degenerative disease other than AMD.
  • Subject has a prior history of retinal detachment within the vascular arcades.
  • Subject has nevus of Ota (oculodermal melanocytosis), a choroidal pigmented lesion showing characteristics associated with high risk of malignancy (e.g., orange pigmented or elevated lesions) or a choroidal nevus within the macula.
  • Subject has presence of submacular scarring.
  • Subject has presence of an ocular toxoplasmosis scar or suspected active infection (or presence of elevated immunoglobulin M [IgM] toxoplasmosis titer).
  • Subject has an abnormality of vitreoretinal interface (i.e., vitreomacular traction, epiretinal membranes, etc.) which can interfere with measurement of macular thickness or with the potential for macular structural damage.
  • Subject has an intraocular pressure (IOP) of < 6 mmHg at the screening or first baseline (day -21) visits.
  • Subject has presence of glaucomatous optic atrophy or uncontrolled intraocular pressure (IOP), or is using more than 2 agents to control IOP.
  • Subject has active or history of uveitis.
  • Subject has obscured ocular media opacity (e.g., corneal scars, lens opacities, vitreous abnormalities, etc.) at the screening or first baseline (day -21) visits such that reliable evaluations of the posterior segment cannot be performed.
  • Subject has any other current ocular condition that can interfere with the assessment of disease progression including but not limited to accumulation of intraretinal fluid, subretinal fluid, sub-retinal pigment epithelial/epithelium (RPE) fluid or cyctoid macular edema.
  • Subject has monocular vision.
  • Subject has a history of ocular cancer in either eye.

Other Medical Conditions:

  • Subject has a history of severe allergic reaction to fluorescein (e.g., hives or anaphylaxis) or inadequate venous access for FA.
  • Subject has a history of recurrent varicella-zoster virus (VZV) infection or a clinical diagnosis of VZV infection within 4 weeks of the baseline day -21 visit.
  • Subject has a history of recurrent cytomegalovirus (CMV) infection or a clinical diagnosis of CMV infection within 4 weeks of the baseline day -21 visit.
  • Subject has received a solid organ or bone marrow transplant.
  • Subject has an active, extraocular infection requiring the prolonged or chronic use of antimicrobial or antiinfective agents.
  • Subject has a current malignancy or is being treated for malignancy. Subject with a history of malignancy that has been treated successfully may be included.
  • Subject has a history of familial adenomatous polyposis.
  • Subject has a history of myocardial infarction in previous 12 months and whom disease is either unstable and/or symptomatic (e.g., angina, dyspnea, etc.).
  • Subject has any abnormality in Electrocardiogram (ECG) results that is clinically significant and could either jeopardize the safety of the subject, impact the subject's ability to comply with study visit schedule or impact the validity of the study results. Note: Subjects with a mean Fridericia-corrected QT interval (QTcF) of > 430 ms (for males) and > 450 ms (for females) at screening must be cleared by a cardiologist prior to the first baseline visit (day -21).
  • Subject has a study day diastolic blood pressure > 95 mmHg, at either the screening or first baseline (day -21) visit.
  • Subject has any condition that would prohibit the use of systemic immunosuppression with Prograf and MMF.
  • Subject has inflammatory bowel disease (e.g., clinically diagnosed irritable bowel syndrome, Crohn's disease, ulcerative colitis).
  • Subject has a positive tuberculosis (TB) test during the screening period by an interferon gamma release assay (e.g., QuantiFERON). If a subject has tested negative for TB within the 6 months prior to the screening visit, retesting is not required unless clinically indicated.
  • Subject has a history of or current condition that will interfere with the subject's ability to comply with the protocol, compromise subject safety or interfere with the interpretation of the study results (e.g., cognitive impairment, dementia, active substance abuse, uncontrolled psychiatric disorder or elective treatment).

Prior and Concomitant Ocular Therapies:

The following conditions are exclusionary if present in the study eye, if applicable.

  • Subject has received prior treatment with anti-vascular endothelial growth factor (VEGF) (for any indication) within 12 weeks prior to the screening visit or anticipated use at any point during the study.
  • Subject has received prior intravitreal treatment other than anti-VEGF treatment.
  • Subject has undergone intraocular surgery or refractive surgery within 12 weeks prior to the screening visit.
  • Subject is anticipated to require ocular surgery prior to completing the 26-week visit or any ocular treatment, which could confound the efficacy results or affect subject compliance with the visit schedule.
  • Subject has any history of an ocular implant, with the exception of an intraocular lens.
  • Subject has undergone prior retinal surgery involving the macula, vitrectomy, macular laser photocoagulation, external-beam radiation therapy, transpupillary thermotherapy, glaucoma filtration surgery or corneal surgery (except cataract surgery).

Prior and Concomitant Therapy:

  • Subject has received gene transfer or cell transplant therapy in a prior clinical trial.
  • Subject has participated within 12 weeks prior to the screening visit in any clinical trial of a drug by ocular or systemic administration and/or has not recovered from any reversible effects or side effects of a prior investigational agent.
  • Subject is receiving or has received any 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-lifes, whichever is longer, prior to the administration of adjunct study medication.
  • Subject is unwilling to discontinue or avoid any CYP3A4 inducers (e.g., rifampin, rifabutin, phenytoin, carbamazepine, phenobarbital, St. John's wort) or subject is unwilling to discontinue or avoid protease inhibitors (e.g., nelfinavir, telaprevir, boceprevir), direct Factor Xa inhibitors, direct thrombin inhibitors, verapamil, diltiazem or erythromycin while taking Prograf.
  • Subject is unwilling to discontinue cholestyramine and azathioprine while the subject is taking MMF.

Clinical Laboratory Tests:

The following are exclusionary if observed at the screening visit.

  • Subject has any abnormality in blood chemistry, urinalysis or hematology results that is clinically significant and prohibits participation in the study.
  • Subject has an estimated glomerular filtration rate (eGRF) of ≤ 45 mL/min, calculated by the chronic kidney disease epidemiology collaboration (CKD-EPI) equation.
  • Subject has an alanine aminotransferase (ALT), aspartate aminotransferase (AST) or gamma-glutamyltransferase (GGT) and total bilirubin (TBL) ≥ 2 times the upper limit of normal (ULN).
  • Subject has severe anemia (hemoglobin < 9 g/dL [male] or hemoglobin < 8 g/dL [female]), leucopenia (white blood cell count < 2500/mm3), thrombocytopenia (platelet count < 80000/mm3) or polycythemia (hematocrit > 54% [male] or hematocrit > 49% [female]).
  • Subject has a hemoglobin A1c > 8.5%.
  • Subject 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).
  • Subject has serology result indicative of having syphilis, Lyme disease, human immunodeficiency virus (HIV) infection or active infection with hepatitis A, B or C virus (HAV, HBV or HCV, respectively).
  • Subject has a positive urine screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, opiates, cocaine, phencyclidine and methadone), unless the drug is taken for a documented medical condition and under the supervision of a physician.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Astellas Institute for Regenerative Medicine 800-888-7704 astellas.registration@astellas.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03178149
Other Study ID Numbers  ICMJE 7317-CL-0003
2016-005099-87 ( EudraCT Number )
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  ICMJE
Plan to Share IPD: Undecided
Responsible Party Astellas Pharma Inc ( Astellas Institute for Regenerative Medicine )
Study Sponsor  ICMJE Astellas Institute for Regenerative Medicine
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Global Therapeutic Area Head & Chief Medical Officer Astellas Institute for Regenerative Medicine
PRS Account Astellas Pharma Inc
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP