A Safety Study of CNTO 2476 in Patients With Age-Related Macular Degeneration

This study has suspended participant recruitment.
(Study on hold due to the review of a study related procedure)
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01226628
First received: October 21, 2010
Last updated: January 22, 2014
Last verified: January 2014
  Purpose

The main purpose of this study to evaluate the safety and tolerability of CNTO 2476 administered subretinally (beneath the retina) using the iTrack Model 275 micro catheter in patients with visual acuity (acuteness or clearness of vision) impairment associated with the geographic atrophy (GA: partial or complete wasting away of retinal layer below the retina) manifestation of age-related macular degeneration (AMD: medical condition which usually affects older adults and results in a loss of vision in the center of the visual field [the macula] because of damage to the retina).


Condition Intervention Phase
Age-related Macular Degeneration
Biological: CNTO 2476
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1/2a, Multicenter, Randomized, Dose Escalation, Fellow-Eye Controlled, Study Evaluating the Safety and Clinical Response of a Single, Subretinal Administration of Human Umbilical Tissue-Derived Cells (CNTO 2476) in Subjects With Visual Acuity Impairment Associated With Geographic Atrophy Secondary to Age-related Macular Degeneration

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Number of eyes with serious ocular adverse events occurring over the first 12 months of the study [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    This number will be summarized descriptively for treated and fellow eyes within each dose level included in Phase 1 and Phase 2a portions of the study


Secondary Outcome Measures:
  • Change from baseline in antibody peak values [ Time Frame: Baseline (Screening), up to 60 months ] [ Designated as safety issue: No ]
  • Yearly rate of increase from baseline in area of Geographic Atrophy (GA) [ Time Frame: Baseline (Screening), up to 60 months ] [ Designated as safety issue: No ]
  • Changes from baseline in visual function [ Time Frame: Baseline (Screening), up to 60 months ] [ Designated as safety issue: No ]
    Changes from baseline in visual function is measured as changes in best corrected visual acuity [BCVA], low luminance BCVA, low luminance deficit, reading speed, contrast threshold, visual field and retinal thickness measured by spectral-domain optical coherence tomography (SD-OCT) at registered sections of the macula that include the geographic atrophy and adjacent retina

  • Change from baseline in Visual Functioning Questionnaire (VFQ)-25 [ Time Frame: Baseline (Screening), up to 60 months ] [ Designated as safety issue: No ]
    The VFQ-25 is a reliable and validated 25-item version of the larger 51-item National Eye Institute Visual Function Questionnaire. The questionnaire must be administered by the study staff and must not be self-administered. Analysis of VFQ-25 questionnaire data will be based on the thirteen sub-scales and a composite score.

  • Incidence of adverse events [ Time Frame: up to 60 months ] [ Designated as safety issue: Yes ]
    Incidence of adverse events will be assessed in both Phases (Phase 1 and Phase 2a)


Estimated Enrollment: 68
Study Start Date: September 2010
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A
Phase 1: 3 patients will receive 60,000 human umbilical tissue-derived cells (hUTC)
Biological: CNTO 2476
Other Name: Human umbilical tissue-derived cells (hUTC)
Experimental: Cohort B
Phase 1: 3 patients will receive 120,000 hUTC
Biological: CNTO 2476
Other Name: Human umbilical tissue-derived cells (hUTC)
Experimental: Cohort C
Phase 1: 3 patients will receive 300,000 hUTC
Biological: CNTO 2476
Other Name: Human umbilical tissue-derived cells (hUTC)
Experimental: Cohort D
Phase 1: 3 patients will receive 560,000 hUTC
Biological: CNTO 2476
Other Name: Human umbilical tissue-derived cells (hUTC)
Experimental: Cohort E
Phase 1: 6 patients will receive 300,000 hUTC
Biological: CNTO 2476
Other Name: Human umbilical tissue-derived cells (hUTC)
Experimental: Cohort F
Phase 1: 6 patients will receive either 60,000 or 300,000 hUTC
Biological: CNTO 2476
Other Name: Human umbilical tissue-derived cells (hUTC)
Experimental: Cohort G
Phase 1: 6 patients will receive either 60,000 or 300,000 hUTC
Biological: CNTO 2476
Other Name: Human umbilical tissue-derived cells (hUTC)
Experimental: Phase 2a
Up to 38 patients will receive one of two optimal doses as selected from the Phase 1 portion of the study
Biological: CNTO 2476
Other Name: Human umbilical tissue-derived cells (hUTC)

Detailed Description:

The study is a Phase 1/2a, multicenter, randomized (the study medication is assigned by chance), single dose, dose escalation, fellow-eye controlled study evaluating the safety and clinical response of a single, subretinal administration of CNTO 2476 in patients with visual acuity impairment associated with GA secondary to AMD. The study will consist of screening (up to 21 days prior to treatment) period, treatment (Day 1) period and follow up period. The study will be conducted in 2 portions: the Phase 1 portion will include dose escalation and the Phase 2 portion will enroll additional patients randomized to one of the 2 optimal doses selected from the Phase 1 portion (with an acceptable safety profile seen in Phase 1). For Phase 1, the treatment eye will be the eye with worse visual acuity or the one chosen by the investigator, however, the treatment eye cannot have a visual acuity no better than 20/200. For Phase 2a, the treatment eye will be the eye with worse visual acuity, and cannot have a visual acuity better than 20/80. Approximately 30 patients will participate in the Phase 1 dose escalation portion, and 38 patients will be enrolled in the Phase 2a portion (19 patients receiving optimal dose level X from Phase 1 and 19 receiving optimal dose level Y from Phase 1). In the Phase 1 portion, treatment will be assigned 5 sequential cohorts, with 3 patients per cohort in each of the first 4 cohorts and 6 patients in the fifth cohort. Cohort A patients will be treated first, followed by Cohort B patients. All patients in a given cohort must have completed at least 4 weeks of post-treatment follow-up before patients in the next cohort may be treated. Follow-up will include postoperative follow-up period of 12 months (Day 2, Day 7, Day 15, Week 3, Week 4, Months 2, 3, 6, and 12) and long-term safety follow-up period of 4 years (patients will be evaluated every 6 months for safety assessments). Safety assessments will include vital signs, AEs, and concomitant medications and routine 12-lead electrocardiograms (ECG). The anticipated study duration will be approximately 5 years (1 year in the 12-month postoperative follow-up period; 4 years in the long-term safety follow-up period).

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women must be incapable of childbearing
  • Patient must be a suitable candidate for ophthalmologic surgery, is willing and able to comply with the surgical procedure, scheduled visits, treatment plan, laboratory tests and other study procedures
  • Confirmed diagnosis of bilateral geographic atrophy (GA) of the macula bilaterally caused by age-related macular degeneration

Exclusion Criteria:

  • Evidence of exudative ("wet") age -related macular degeneration in either eye
  • Evidence of other significant ophthalmologic disease (eg, glaucoma)
  • Ocular hypertension
  • Previous cell therapy other than blood components
  • Previous treatment for age-related macular degeneration (AMD) other than antioxidant or zinc supplements or other oral vitamin supplements
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01226628

Locations
United States, California
Arcadia, California, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01226628     History of Changes
Other Study ID Numbers: CR017548, CNTO2476MDG1002
Study First Received: October 21, 2010
Last Updated: January 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:
Macular degeneration
Age-related macular degeneration
Cell therapy
CNTO 2476
Human umbilical tissue-derived cells
hUTC
Geographic Atrophy
Subretinal
Visual Acuity

Additional relevant MeSH terms:
Macular Degeneration
Geographic Atrophy
Retinal Degeneration
Retinal Diseases
Eye Diseases

ClinicalTrials.gov processed this record on September 30, 2014