Clinical trial NCT01835015: Pharmacokinetics of CLG561 in Patients With Advanced Age-Related Macular Degeneration
Official title: A Multi-Center, Open-Label, Single Ascending Dose Study To Assess the Safety, Tolerability, and Serum Pharmacokinetics of Intravitreal CLG561 in Subjects With Advanced Age-Related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Age-related Macular Degeneration
Keywords: First in human
Safety
Tolerability
Serum PK
Intravitreal (IVT)
Age-related macular degeneration
AMD
Geographic Atrophy
Choroidal neovascularization
Lead sponsor: Alcon Research
Sponsor class: INDUSTRY
First posted: 2013-04-18
Enrollment: 50
Sex: ALL
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to evaluate the safety, tolerability, and serum pharmacokinetics of CLG561 in subjects with advanced age-related macular degeneration (AMD).

Detailed description: Subjects were divided into 5 cohorts, with the subjects in each cohort being administered a single IVT dose of CLG561 in 1 of 5 concentration levels A-E, where A=lowest and E=highest. All subjects received active CLG561. Progress from one cohort to the next was time-lagged to allow for safety review. Dosing was also time-lagged within each cohort. Only one eye (designated as the study eye) was dosed per subject. Post-dose safety assessments and ocular examination occurred immediately after the IVT injection and continued throughout the outpatient visits at pre-determined timepoints. Collection of post-injection blood samples began after the IVT injection at pre-determined timepoints. Subjects were followed for up to 84 days.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of age-related macular degeneration in study eye, as specified in protocol.
* Poor visual acuity in study eye, as specified in protocol.
* Willing to receive meningitis and pneumonia vaccinations at least 2 weeks prior to study treatment.
* Females must be post-menopausal and/or surgically sterile.
* Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

* Treatments to the study eye within 28 days prior to study treatment, as specified in protocol.
* Any disease or medication expected to cause systemic or ocular immunosuppression.
* Participation in another interventional clinical study or use of any experimental treatment for AMD within 12 weeks prior to study treatment.
* Other protocol-defined exclusion criteria may apply.

Primary outcomes:
measure: Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye
timeFrame: Baseline, Day 2, Day 4, Day 15, Day 29, Day 57, Day 85
measure: Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye
timeFrame: Baseline, Day 1, Day 2, Day 4, Day 15, Day 29, Day 57, Day 85
measure: Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment
timeFrame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 29, Day 57, Day 85
measure: Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment
timeFrame: Baseline, Day 2, Day 4, Day 8, Day 15, Day 29, Day 57, Day 85
Secondary outcomes:
measure: Area Under the Serum Concentration-time Curve (AUC) From Time Zero to All [AUC(0-all)]
timeFrame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
measure: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)]
timeFrame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
measure: Time to Reach the Maximum Serum Concentration After Drug Administration (Tmax)
timeFrame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
measure: Dose Normalized Observed Maximum Serum Concentration Following Drug Administration (Cmax/D)
timeFrame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
measure: Dose-normalized Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)/D]
timeFrame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
measure: Area Under the Serum Concentration-time Curve From Time Zero to Time "t" Where t is a Defined Time Point After Administration [AUC(0-t)]
timeFrame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
measure: Terminal Elimination Half-life (T½)
timeFrame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
measure: The Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration (Vz/F)
timeFrame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
measure: Apparent Systemic (or Total Body) Clearance From Serum Following Extravascular Administration (CL/F)
timeFrame: Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85
Other outcomes:
Locations:
Study officials:
affiliation: Alcon Research
name: Head of Clinical Sciences, CA CSI NS/Opth
role: STUDY_DIRECTOR
References: