Clinical trial NCT02530918: Study of DS-7080a for the Treatment of Macular Degeneration
Official title: Phase I Dose Escalation and Expansion Study of DS-7080a in Subjects With Neovascular Age-related Macular Degeneration or Diabetic Macular Edema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neovascular Age-Related Macular Degeneration
Diabetic Macular Edema
Keywords: DS-7080a Monoclonal Antibody
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2015-08-21
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Sequential Assignment with 3 cohorts in Part 1, Parallel Assignment with 3 arms in Part 2, and Parallel Assignment with 2 arms in Part 3
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test DS-7080a, a monoclonal antibody, as a new treatment for neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME). The hypothesis of the study is that DS-7080a is safe and shows preliminary efficacy in patients with these conditions either alone or in combination with ranibizumab. This study is organized into 3 Parts: Part 1 Dose Escalation in AMD participants, Part 2 Dose Expansion in AMD participants, and Part 3 Dose Expansion in DME participants.

In Part 1, participants will be enrolled into 3 sequential, ascending dose-level cohorts in non-randomized uncontrolled manner with the main purpose to determine the recommended dose.

In Part 2, participants will be randomized to 1 of 3 arms of either monotherapy with DS-7080a or monotherapy with ranibizumab, which is an active control, or combination therapy of DS-7080a plus ranibizumab (ranibizumab will be administered 30 minutes prior to DS-7080a).

In Part 3, subjects with DME will be assigned to 1 of 2 arms of either monotherapy with DS-7080a or monotherapy with ranibizumab. DS-7080a or ranibizumab will be administered 3 times: on Baseline/Day 1, Day 29, and Day 57.

Both Parts 2 and 3 will consist of 8 visits including a 14-day screening phase, an 84-day treatment period, and a 28-day follow-up period.


Eligibility criteria: Inclusion Criteria:

For parts 1 and 2:

* ≥ 50 years of age
* Has active primary subfoveal choroid neovascularization (CNV) lesions secondary to age-related macular degeneration (AMD)
* CNV ≥ 50% of total lesion size in study eye
* Central sub-field thickness \> 315 µm on spectral domain optical coherence tomography (SD-OCT) in the study eye
* Has BCVA letter score required at screening visit:
* For Part 1, ≤ 49 (approximately 20/100 or worse) in the study eye and ≥ 49 (approximately 20/100 or better) in the fellow eye
* For Part 2, 78 to 25 (approximately 20/32 to 20/320) in the study eye

For Part 3:

* Is ≥ 18 years of age with retinal thickening due to diabetic macular edema (DME)
* Has central sub-field thickness (CST) \> 335 μm in the study eye
* Has BCVA letter score at screening visit 78 to 25 letters (approximately 20/32 to 20/320) in the study eye

Exclusion Criteria:

For Parts 1 and 2:

* Has used any long acting steroids, either systemically or intraocularly, within 6 months of Baseline Visit
* Has total lesion size \> 12 disc areas (30.5 mm2) in the study eye
* Has presence of retinal pigment epithelial tears or rips involving the macula in the study eye
* Has history of any vitreous hemorrhage within 4 weeks prior to Screening Visit in the study eye
* Has presence of causes of CNV other than AMD
* Had prior vitrectomy in the study eye
* Has history of retinal detachment or treatment or surgery for retinal detachment in the study eye
* Has any history of a full thickness macular hole in the study eye
* Had any intraocular or periocular surgery within 3 months of Baseline Visit on the study eye, except lid surgery
* Has uncontrolled glaucoma in the study eye
* Has active intraocular inflammation or periocular infection in either eye
* Has any history of uveitis in either eye of scleromalacia in either eye
* Has aphakia or pseudophakia in the study eye
* Had previous therapeutic radiation in the region of the study eye
* Has history of corneal transplant or corneal dystrophy in the study eye
* Has significant media opacities in the study eye (e.g. cataract) that could require either medical or surgical intervention during the study period
* Is a women who is pregnant, breastfeeding, or of childbearing potential and unwilling to practice two measures of adequate contraception throughout the study

For Part 1 only:

* Had any ocular (in the study eye) or systemic treatment or surgery for neovascular AMD within 4 weeks of Baseline Visit, except dietary supplements or vitamins
* Has a subretinal hemorrhage that is ≥ 50% of the total lesion area in the study eye
* Has scarring or fibrosis, making up \>50% of total lesion or involving the center of the fovea in the study eye

For Part 2 only:

* Had any prior therapy in the study eye within 3 months of Baseline Visit, except dietary supplements or vitamins

For Part 3:

* Has used any steroids, either systemically or ocular in the study eye (other than fluocinolone), within 6 months of Baseline Visit
* Has macular edema in the study eye considered to be due to a cause other than DME
* Has high-risk proliferative diabetic retinopathy (PDR) in the study eye
* Has decrease in BCVA in the study eye due to causes other than DME
* Has significant macular ischemia in the study
* Has choroidal neovascularization (CNV) secondary to any etiology
* Has retinal pigment epithelial tears or rips involving the macula in the study eye
* Had any vitreous hemorrhage within 4 weeks prior to Screening/Visit 1 in the study eye
* Had prior vitrectomy in the study eye
* Has history of retinal detachment or treatment or surgery for retinal detachment in the study eye
* Has history of a full thickness macular hole in the study eye
* Had any intraocular or periocular surgery within 3 months of Baseline Visit
* Has uncontrolled glaucoma in the study eye
* Had prior trabeculectomy or other filtration surgery in the study eye
* Has active intraocular inflammation or periocular infection in either eye
* Has current or history of scleromalacia in either eye
* Has aphakia or pseudophakia with absence of posterior capsule
* Has previous therapeutic radiation in the region of the study eye
* Has history of corneal transplant or corneal dystrophy in the study eye
* Has concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the subject beyond what is to be expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of safety, tolerability, or efficacy
* Has systolic blood pressure ≥160 mmHg and/or a diastolic blood pressure ≥95 mmHg at Screening
* Has an estimated Glomerular Filtration Rate (eGFR) of \< 15 mL/min/1.73 m\^2 as per the creatinine equation (CKD-EPI) at Screening
* Has any history of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk for treatment complications
* Is a women who is pregnant, breastfeeding, or of childbearing potential and unwilling to practice two measures of adequate contraception throughout the study

Primary outcomes:
measure: Number of participants experiencing any treatment-emergent adverse event (TEAE)
timeFrame: 16 weeks
measure: Best Corrected Visual Acuity (BCVA) score
timeFrame: 12 weeks
Secondary outcomes:
measure: Change from baseline in retinal thickness and volume
timeFrame: 12 weeks
measure: Change from baseline in retinal leakage
timeFrame: 12 weeks
measure: Plasma concentrations
timeFrame: 12 weeks
measure: Part 3 only: Change from baseline in vessel flow density, foveal avascular zone (FAZ) area, and FAZ shape
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Arcadia
country: United States
state: California
city: Beverly Hills
country: United States
state: California
city: Palm Desert
country: United States
state: California
city: Fort Myers
country: United States
state: Florida
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Omaha
country: United States
state: Nebraska
city: Abilene
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Silverdale
country: United States
state: Washington
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: