Clinical trial NCT01226628: A Safety Study of CNTO 2476 in Patients With Age-Related Macular Degeneration
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Age-related Macular Degeneration
Keywords: Macular degeneration
Age-related macular degeneration
Cell therapy
CNTO 2476
Human umbilical tissue-derived cells
hUTC
Geographic Atrophy
Subretinal
Visual Acuity
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2010-10-22
Enrollment: 39
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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 (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; up to 4 years in the long-term safety follow-up period).

Eligibility 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

Primary outcomes:
measure: Number of eyes with serious ocular adverse events occurring over the first 12 months of the study
timeFrame: 12 months
Secondary outcomes:
measure: Change from baseline in antibody peak values
timeFrame: Baseline (Screening), up to 60 months
measure: Yearly rate of increase from baseline in area of Geographic Atrophy (GA)
timeFrame: Baseline (Screening), up to 60 months
measure: Changes from baseline in visual function
timeFrame: Baseline (Screening), up to 60 months
measure: Change from baseline in Visual Functioning Questionnaire (VFQ)-25
timeFrame: Baseline (Screening), up to 60 months
measure: Incidence of adverse events
timeFrame: up to 60 months
Other outcomes:
Locations:
city: Arcadia
country: United States
state: California
city: Philadelphia
country: United States
state: Pennsylvania
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: