Study of DS-7080a for the Treatment of Macular Degeneration

NCT02530918 | Completed Phase 1

• 1 other identifier: DS7080-A-U101
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 12

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.

Conditions

Neovascular Age-Related Macular Degeneration; Diabetic Macular Edema

Keywords

DS-7080a Monoclonal Antibody

Outcome Measures

Primary Outcomes (2)

• Number of participants experiencing any treatment-emergent adverse event (TEAE)

  Treatment-emergent AEs (TEAEs) are defined as those adverse events (AEs) that were new or got worse between the start of study treatment and the end of the follow-up period.

  16 weeks

• Best Corrected Visual Acuity (BCVA) score

  Visual acuity of both eyes will be assessed at all study visits using the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score. The patient starts are the top of the chart and begins to read down the chart. The patient reads down the chart until he or she reaches a row where a minimum of three letters on a line cannot be read. The patient is scored by how many letters could be correctly identified. Added to the score for the last row where the participant could read all five letters correctly are scores for each additional letter that could be read correctly in the next row. This is the BCVA score. A higher score means better visual acuity (sharpness of vision).

  12 weeks

Secondary Outcomes (4)

• Change from baseline in retinal thickness and volume

  12 weeks

• Change from baseline in retinal leakage

  12 weeks

• Plasma concentrations

  12 weeks

• Part 3 only: Change from baseline in vessel flow density, foveal avascular zone (FAZ) area, and FAZ shape

  12 weeks

Study Arms (6)

Part 1 DS-7080a dose escalation

EXPERIMENTAL

3 sequential ascending dose levels (1.0, 2.0, 4.0 mg), every 4 weeks for 12 weeks

Drug: DS-7080a

Part 2 DS-7080a

EXPERIMENTAL

Specific dose (either the maximum tolerated dose or 4.0 mg) of DS-7080a determined in Part 1, every 4 weeks for 12 weeks

Drug: DS-7080a

Part 2 ranibizumab

ACTIVE COMPARATOR

Ranibizumab 0.5 mg, every 4 weeks for 12 weeks

Drug: Ranibizumab

Part 2 DS-7080a and ranibizumab

EXPERIMENTAL

Specific dose of DS-7080a determined in Part 1 and ranibizumab 0.5 mg, every 4 weeks for 12 weeks

Drug: DS-7080a; Drug: Ranibizumab

Part 3 DS-7080a

EXPERIMENTAL

Specific dose of DS-7080a determined in Part 1, every 4 weeks for 12 weeks

Drug: DS-7080a

Part 3 ranibizumab

EXPERIMENTAL

Ranibizumab 0.3 mg, every 4 weeks for 12 weeks

Drug: Ranibizumab

Interventions

DS-7080a DRUG

1.0, 2.0, or 4.0 mg administered by a 50 μL intravitreal (IVT) injection of solution

Also known as: Investigational product

Part 1 DS-7080a dose escalation; Part 2 DS-7080a; Part 2 DS-7080a and ranibizumab; Part 3 DS-7080a

Ranibizumab DRUG

0.3 mg or 0.5 mg administered by a 50 μL IVT injection of solution

Also known as: Lucentis

Part 2 DS-7080a and ranibizumab; Part 2 ranibizumab; Part 3 ranibizumab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (12)

Unknown Facility

Phoenix, Arizona, 85014, United States

Location

Unknown Facility

Arcadia, California, 91007, United States

Location

Unknown Facility

Beverly Hills, California, 90211, United States

Location

Unknown Facility

Palm Desert, California, 92260, United States

Location

Unknown Facility

Fort Myers, Florida, 33912, United States

Location

Unknown Facility

Baltimore, Maryland, 21237, United States

Location

Unknown Facility

Boston, Massachusetts, 02114, United States

Location

Unknown Facility

Omaha, Nebraska, 68105, United States

Location

Unknown Facility

Abilene, Texas, 79606, United States

Location

Unknown Facility

Austin, Texas, 78705, United States

Location

Unknown Facility

San Antonio, Texas, 78240, United States

Location

Unknown Facility

Silverdale, Washington, 98383, United States

Location

MeSH Terms

Interventions

Ranibizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Study Design

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

Model Details: 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

Study Record Dates

• First Submitted: August 17, 2015
• First Posted: August 21, 2015
• Study Start: July 1, 2015
• Primary Completion: January 2, 2018
• Study Completion: January 2, 2018
• Last Updated: May 9, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Studies for which the medicine and indication have received EU and US marketing approval on or after 01 January 2014 or by the US or EU Health Authorities when regulatory submissions in both regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States and the European Union from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

US (12)