Trial Outcomes & Findings for Infliximab, Sirolimus and Daclizumab to Treat Age-Related Macular Degeneration (NCT NCT00304954)

NCT ID: NCT00304954

Last Updated: 2016-11-29

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

24 Weeks

Results posted on

2016-11-29

Participant Flow

The study was conducted at the Clinical Center, NIH. A total of 13 participants met the eligibility criteria for the study and were enrolled from September 2006 to May 2008.

Participant milestones

Participant milestones
Measure	Intravenous Daclizumab Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study.	Intravenous Infliximab Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months.	Oral Rapamycin Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months.	Observation Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography.
Overall Study STARTED	4	3	3	3
Overall Study COMPLETED	3	3	2	3
Overall Study NOT COMPLETED	1	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Intravenous Daclizumab Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study.	Intravenous Infliximab Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months.	Oral Rapamycin Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months.	Observation Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography.
Overall Study Withdrawal by Subject	0	0	1	0
Overall Study Adverse Event	1	0	0	0

Baseline Characteristics

Infliximab, Sirolimus and Daclizumab to Treat Age-Related Macular Degeneration

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intravenous Daclizumab n=4 Participants Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study.	Intravenous Infliximab n=3 Participants Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months.	Oral Rapamycin n=3 Participants Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months.	Observation n=3 Participants Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography.	Total n=13 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	12 Participants n=21 Participants
Age, Continuous	79 years STANDARD_DEVIATION 13 • n=5 Participants	77 years STANDARD_DEVIATION 8 • n=7 Participants	78 years STANDARD_DEVIATION 7 • n=5 Participants	87 years STANDARD_DEVIATION 4 • n=4 Participants	80 years STANDARD_DEVIATION 9 • n=21 Participants
Gender Female	4 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	12 Participants n=21 Participants
Gender Male	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment United States	4 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	3 participants n=4 Participants	13 participants n=21 Participants

PRIMARY outcome

Timeframe: 24 Weeks

Outcome measures

Outcome measures
Measure	Intravenous Daclizumab n=4 Participants Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study.	Intravenous Infliximab n=3 Participants Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months.	Oral Rapamycin n=3 Participants Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months.	Observation n=3 Participants Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography.
Monthly Rates of Anti-VEGF (Vascular Endothelial Growth Factor) Injections	0.42 Injections per Month Interval 0.34 to 0.83	0.83 Injections per Month Interval 0.5 to 1.0	0.34 Injections per Month Interval 0.29 to 0.5	0.83 Injections per Month Interval 0.5 to 1.0

SECONDARY outcome

Timeframe: Baseline and 6 months (24 weeks) - Baseline and 3.5 months for Patient 7

The values in the table represent the denominator for the visual acuity in feet. A value of 20 represents "normal" 20/20 vision while increasing values for the denominator represent worsening vision.

Outcome measures

Outcome measures
Measure	Intravenous Daclizumab n=13 Participants Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study.	Intravenous Infliximab n=13 Participants Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months.	Oral Rapamycin n=13 Participants Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months.	Observation n=13 Participants Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography.
Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks Rapamycin Patient 1	40 Feet	25 Feet	400 Feet	640 Feet
Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks Rapamycin Patient 7 (Baseline and 3.5 months)	63 Feet	50 Feet	640 Feet	640 Feet
Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks Rapamycin Patient 12t	32 Feet	32 Feet	32 Feet	32 Feet
Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks Daclizumab Patient 3	40 Feet	40 Feet	40 Feet	32 Feet
Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks Daclizumab Patient 8	32 Feet	32 Feet	32 Feet	32 Feet
Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks Daclizumab Patient 9	250 Feet	250 Feet	63 Feet	40 Feet
Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks Daclizumab Patient 13	50 Feet	40 Feet	25 Feet	20 Feet
Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks Infliximab Patient 2	40 Feet	32 Feet	63 Feet	125 Feet
Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks Infliximab Patient 6	250 Feet	800 Feet	63 Feet	80 Feet
Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks Infliximab Patient 10	50 Feet	32 Feet	125 Feet	125 Feet
Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks Observation Patient 4	63 Feet	63 Feet	40 Feet	25 Feet
Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks Observation Patient 5	50 Feet	25 Feet	NA Feet Vision too low to arrive at value. Counting fingers used instead.	NA Feet Vision too low to arrive at value. Counting fingers used instead.
Changes in Best-corrected Visual Acuity (BCVA) as Measured by the Standard Early Treatment Diabetic Retinopathy Study (ETDRS) Protocol From Baseline to 24 Weeks Observation Patient 11	32 Feet	50 Feet	200 Feet	63 Feet

SECONDARY outcome

Timeframe: Baseline and 6 months (24 weeks) - Baseline and 3.5 months for Patient 7

Outcome measures

Outcome measures
Measure	Intravenous Daclizumab n=13 Participants Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study.	Intravenous Infliximab n=13 Participants Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months.	Oral Rapamycin n=13 Participants Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months.	Observation n=13 Participants Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography.
Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks Daclizumab Patient 3	216 Microns	189 Microns	352 Microns	206 Microns
Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks Daclizumab Patient 8	185 Microns	208 Microns	218 Microns	149 Microns
Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks Observation Patient 5	426 Microns	225 Microns	270 Microns	213 Microns
Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks Observation Patient 11	318 Microns	305 Microns	158 Microns	169 Microns
Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks Rapamycin Patient 1	234 Microns	230 Microns	211 Microns	203 Microns
Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks Rapamycin Patient 7 (Baseline and 3.5 months)	361 Microns	239 Microns	242 Microns	186 Microns
Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks Rapamycin Patient 12t	327 Microns	264 Microns	226 Microns	205 Microns
Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks Daclizumab Patient 9	297 Microns	196 Microns	215 Microns	210 Microns
Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks Daclizumab Patient 13	329 Microns	344 Microns	305 Microns	317 Microns
Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks Infliximab Patient 2	205 Microns	177 Microns	190 Microns	181 Microns
Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks Infliximab Patient 6	290 Microns	243 Microns	262 Microns	252 Microns
Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks Infliximab Patient 10	291 Microns	288 Microns	453 Microns	347 Microns
Changes in Retinal Thickness as Measured by Optical Coherence Tomography (OCT) From Baseline to 24 Weeks Observation Patient 4	229 Microns	196 Microns	189 Microns	171 Microns

Adverse Events

Intravenous Daclizumab

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Intravenous Infliximab

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Oral Rapamycin

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Observation

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Intravenous Daclizumab n=4 participants at risk Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study.	Intravenous Infliximab n=3 participants at risk Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months.	Oral Rapamycin n=3 participants at risk Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months.	Observation n=3 participants at risk Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography.
Nervous system disorders Episode of right sided numbness	25.0% 1/4 • Number of events 1 • February 14, 2006 through December 30, 2009	0.00% 0/3 • February 14, 2006 through December 30, 2009	0.00% 0/3 • February 14, 2006 through December 30, 2009	0.00% 0/3 • February 14, 2006 through December 30, 2009

Other adverse events

Additional Information

Dr. Robert Nussenblatt, MD, MPH

NEI

Phone: 301-496-3123

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place