Pharmacokinetics of CLG561 in Patients With Advanced Age-Related Macular Degeneration

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

CLG561

About this trial

This is an interventional basic science trial for Age-related Macular Degeneration focused on measuring First in human, Safety, Tolerability, Serum PK, Intravitreal (IVT), Age-related macular degeneration, AMD, Geographic Atrophy, Choroidal neovascularization

Eligibility Criteria

55 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

CLG561, Concentration Level A

CLG561, Concentration Level B

CLG561, Concentration Level C

CLG561, Concentration Level D

CLG561, Concentration Level E

Arm Description

Single 50 μL intravitreal injection of CLG561, Dose Level A

Single 50 μL intravitreal injection of CLG561, Dose Level B

Single 50 μL intravitreal injection of CLG561, Dose Level C

Single 50 μL intravitreal injection of CLG561, Dose Level D

Single 100 μL intravitreal injection of CLG561, Dose Level E

Outcomes

Primary Outcome Measures

Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye

BCVA (with spectacles or other visual corrective devices) using Early Treatment Diabetic Retinopathy Study (ETDRS) testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis.

Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye

IOP was measured by Goldmann applanation tonometry or tonopen, at the discretion of the Investigator, and reported in mmHg (millimeters of mercury). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) contributed to the analysis.

Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment

A dilated fundus examination was performed to evaluate the health of the retina, macula, choroid, and optic nerve. Subjects having a normal baseline evaluation were examined at subsequent visits, and any change from normal to abnormal was recorded. Criteria for reclassifying from normal to abnormal were left to the opinion of the investigators. One eye (study eye) contributed to the analysis. None of the abnormalities were deemed related to the study medication.

Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment

A slit-lamp biomicroscopy examination was performed to evaluate the anterior segment of the eye. Subjects having a normal baseline evaluation were examined at subsequent visits, and any change from normal to abnormal was recorded. Criteria for reclassifying from normal to abnormal were left to the opinion of the investigators. One eye (study eye) contributed to the analysis. None of the abnormalities were deemed related to the study medication.

Secondary Outcome Measures

Area Under the Serum Concentration-time Curve (AUC) From Time Zero to All [AUC(0-all)]

Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.

Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)]

Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental PK method.

Time to Reach the Maximum Serum Concentration After Drug Administration (Tmax)

Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental PK method.

Dose Normalized Observed Maximum Serum Concentration Following Drug Administration (Cmax/D)

Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental PK method.

Dose-normalized Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)/D]

Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental PK method.

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)]

Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method.

Terminal Elimination Half-life (T½)

Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method.

The Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration (Vz/F)

Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method.

Apparent Systemic (or Total Body) Clearance From Serum Following Extravascular Administration (CL/F)

Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method.

Full Information

NCT ID

NCT01835015

First Posted

April 16, 2013

Last Updated

February 24, 2016

Sponsor

Alcon Research

1. Study Identification

Unique Protocol Identification Number

NCT01835015

Brief Title

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

2. Study Status

Record Verification Date

February 2016

Overall Recruitment Status

Completed

Study Start Date

May 2013 (undefined)

Primary Completion Date

November 2014 (Actual)

Study Completion Date

November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Alcon Research

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Age-related Macular Degeneration

Keywords

First in human, Safety, Tolerability, Serum PK, Intravitreal (IVT), Age-related macular degeneration, AMD, Geographic Atrophy, Choroidal neovascularization

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

50 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CLG561, Concentration Level A

Arm Type

Experimental

Arm Description

Single 50 μL intravitreal injection of CLG561, Dose Level A

Arm Title

CLG561, Concentration Level B

Arm Type

Experimental

Arm Description

Single 50 μL intravitreal injection of CLG561, Dose Level B

Arm Title

CLG561, Concentration Level C

Arm Type

Experimental

Arm Description

Single 50 μL intravitreal injection of CLG561, Dose Level C

Arm Title

CLG561, Concentration Level D

Arm Type

Experimental

Arm Description

Single 50 μL intravitreal injection of CLG561, Dose Level D

Arm Title

CLG561, Concentration Level E

Arm Type

Experimental

Arm Description

Single 100 μL intravitreal injection of CLG561, Dose Level E

Intervention Type

Drug

Intervention Name(s)

CLG561

Intervention Description

Administered by intravitreal injection, Day 1

Primary Outcome Measure Information:

Title

Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye

Description

BCVA (with spectacles or other visual corrective devices) using Early Treatment Diabetic Retinopathy Study (ETDRS) testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis.

Time Frame

Baseline, Day 2, Day 4, Day 15, Day 29, Day 57, Day 85

Title

Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye

Description

IOP was measured by Goldmann applanation tonometry or tonopen, at the discretion of the Investigator, and reported in mmHg (millimeters of mercury). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) contributed to the analysis.

Time Frame

Baseline, Day 1, Day 2, Day 4, Day 15, Day 29, Day 57, Day 85

Title

Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment

Description

A dilated fundus examination was performed to evaluate the health of the retina, macula, choroid, and optic nerve. Subjects having a normal baseline evaluation were examined at subsequent visits, and any change from normal to abnormal was recorded. Criteria for reclassifying from normal to abnormal were left to the opinion of the investigators. One eye (study eye) contributed to the analysis. None of the abnormalities were deemed related to the study medication.

Time Frame

Baseline, Day 2, Day 4, Day 8, Day 15, Day 29, Day 57, Day 85

Title

Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment

Description

A slit-lamp biomicroscopy examination was performed to evaluate the anterior segment of the eye. Subjects having a normal baseline evaluation were examined at subsequent visits, and any change from normal to abnormal was recorded. Criteria for reclassifying from normal to abnormal were left to the opinion of the investigators. One eye (study eye) contributed to the analysis. None of the abnormalities were deemed related to the study medication.

Time Frame

Baseline, Day 2, Day 4, Day 8, Day 15, Day 29, Day 57, Day 85

Secondary Outcome Measure Information:

Title

Area Under the Serum Concentration-time Curve (AUC) From Time Zero to All [AUC(0-all)]

Description

Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.

Time Frame