A Study of the Long-term Safety and Efficacy of Adalimumab in Subjects With Intermediate-, Posterior-, or Pan-uveitis

Phase 3

Completed

Conditions: Uveitis

Interventions: Drug: adalimumab

Registration Number: NCT01148225

Lead Sponsor: AbbVie

Brief Summary: The purpose of this study is to evaluate the long term efficacy and safety of adalimumab participants with non-infectious intermediate-, posterior- or pan-uveitis.

Detailed Description: This study was initially planned to run for 78 weeks but was extended for ethical reasons, to avoid leaving participants untreated who had responded well to adalimumab treatment, so that participants were allowed to remain in the study until regulatory and/or reimbursement approval for the treatment of uveitis in adults was obtained for their respective countries. Data were collected through Week 366 (maximum), but because of decreasing sample size that became too small toward the end of the study to allow for meaningful conclusion, data cut off for efficacy analyses (intent to treat \[ITT\] population) occurred at Week 246, as less than 10% of participants in the ITT set had visits beyond this timepoint.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 424

Inclusion Criteria

Participant must have successfully enrolled in either study M10-877 or M10-880 and either met the endpoint of "Treatment Failure" or completed the study

Exclusion Criteria

A participant will be excluded from this study if the participant discontinued from study M10-877 or M10-880 for any reasons other than having a Treatment Failure event
Participant with corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the trial
Participants with intraocular pressure of >= 25 mmHg and on >= 2 glaucoma medications or evidence of glaucomatous optic nerve injury
Participant with proliferative or severe non-proliferative diabetic retinopathy or clinically significant macular edema due to diabetic retinopathy
Participant with neovascular/wet age-related macular degeneration
Participant with abnormality of vitreo-retinal interface (i.e., vitreomacular traction, epiretinal membranes, etc.) with the potential for macular structural damage independent of the inflammatory process
Participant with a systemic inflammatory disease that requires therapy with a prohibited immunosuppressive agent at the time of study entry

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Adalimumab	adalimumab	Participants received open label (OL) adalimumab 40 mg by subcutaneous (SC) injection every other week (eow) until the final visit.

Primary Outcome Measures

Name	Time	Method
Hematology: Number of Participants With Potentially Clinically Significant (PCS) Values	Baseline to Final Visit (Up to 366 weeks)	PCS laboratory values were defined as Common Toxicity Criteria (CTC) according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) v3.0 ≥ Grade 3. Abbreviations used include g=grams; L=liters.
Respiratory Rate (Sitting): Mean Change (Respirations Per Minute) From Baseline To Final Visit	Baseline to Final Visit (Up to 366 weeks)	Respiratory rate (respirations per minute) was measured while the participant was sitting.
Number of Participants With Adverse Events	Baseline to Final Visit (up to 366 weeks)	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event with an onset date on or after the first dose of study drug and up to 70 days after the last dose. See the Adverse Event section for details.
Chemistry: Number of Participants With PCS Values	Baseline to Final Visit (Up to 366 weeks)	PCS laboratory values were defined as Common Toxicity Criteria (CTC) according to the National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) v3.0 ≥ Grade 3. Abbreviations include ALT/SGPT=alanine aminotransferase/serum glutamate pyruvate transaminase; AST/SGOT=aspartate aminotransferase/serum glutamate oxaloacetate transaminase; g/L=grams/liter; mmol/L=millimoles/liter; ULN=upper limit of normal.
Pulse (Sitting): Mean Change (Beats Per Minute) From Baseline To Final Visit	Baseline to Final Visit (Up to 366 weeks)	Heart rate (beats per minute) was measured while the participant was sitting.
Temperature (Sitting): Mean Change (Centigrade) From Baseline To Final Visit	Baseline to Final Visit (Up to 366 weeks)	Temperature was measured while the participant was sitting.
Diastolic and Systolic Blood Pressure (Sitting): Mean Change (mmHg) From Baseline To Final Visit	Baseline to Final Visit (Up to 366 weeks)	Blood pressure was measured while the participant was sitting. Abbreviations used include mmHg=millimeters of mercury.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants in Quiescence Over Time	Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246	Quiescence is defined as no active inflammatory lesions and anterior chamber (AC) cell grade ≤ 0.5+ and vitreous haze (VH) grade ≤0.5+. Participants with active uveitis at study entry could have been in quiescence at Week 0 because all participants were evaluated for uveitis status at the Final/Early Termination visit of the lead-in study and the Week 0 visit could have occurred up to 28 days later during which time the participant's disease status may have changed.
Percentage of Participants With Uveitis Flare Among Participants With Inactive Uveitis at Study Start	366 Weeks	Uveitis flare is defined as no quiescence (active inflammatory lesions and AC cell grade \> 0.5+ and/or VH grade \>0.5+).
Percentage of Participants With Uveitis Flare From Week 8 Through Last Visit Among Participants With Active Uveitis at Study Start	Weeks 8 to 246 (238 Weeks)	Uveitis flare is defined as no quiescence (active inflammatory lesions and AC cell grade \> 0.5+ and/or VH grade \>0.5+).
Percentage of Participants With New Active Inflammatory Lesions or Grade ≥2 in Anterior Chamber (AC) Cells or Grade ≥2 in Vitreous Haze (VH) Over Time	Weeks 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246	Dilated indirect ophthalmoscopy is performed to determine both vitreous haze grading and the absence/presence of inflammatory chorioretinal and/or inflammatory retinal vascular lesions. The number of AC cells observed within a 1 mm \* 1 mm slit beam was recorded for each eye and this number was used to determine the grade according to Standardization of Uveitis Nomenclature (SUN) criteria. Grading of VH was based on the National Eye Institute (NEI) publication which was adapted by the SUN working group. The percentage of participants with new active inflammatory lesions or grade ≥2 in AC cells or grade ≥2 in VH are presented.
Percentage of Participants With Steroid-free Quiescence Over Time	Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246	Steroid-free quiescence is defined as no active inflammatory lesions and AC cell grade ≤ 0.5+ and VH grade ≤0.5+ and no uveitis-related corticosteroids on the day of assessment.
Percentage of Participants in Non-quiescence (With/Without Change in Concomitant Medications Within 5 Days and With/Without Quiescence at Next Visit at Least 8 Weeks After Non-quiescence) Among Participants With Inactive Uveitis at Study Start	366 Weeks	Percentage of participants, without quiescence, with/without change in concomitant medications within 5 days after non-quiescence and with/without quiescence at next visit at least 8 weeks after non-quiescence among participants with inactive uveitis at study start. Quiescence is defined as no active inflammatory lesions and AC cell grade ≤ 0.5+ and VH grade ≤0.5+. Abbreviations used are as follows: CM=concomitant medications; NQ=non-quiescence.
Percentage of Participants in Non-quiescence (With/Without Change in Concomitant Medications Within 5 Days and With/Without Quiescence at Next Visit at Least 8 Weeks After Non-quiescence) Among Participants With Active Uveitis at Study Start	366 Weeks	Percentage of participants, without quiescence, with/without change in concomitant medications within 5 days after non-quiescence and with/without quiescence at next visit at least 8 weeks after non-quiescence, among participants with active uveitis at study start. Quiescence is defined as no active inflammatory lesions and AC cell grade ≤ 0.5+ and VH grade ≤0.5+. Abbreviations used include: CM=concomitant medications, NQ=non-quiescence.
Percentage of Participants Who Started Uveitis-related Systemic Corticosteroids During the Study	366 Weeks	Percentage of participants who started uveitis-related systemic corticosteroids during the study.
Mean Daily Dose in Milligrams (mg) of Uveitis-related Systemic Corticosteroids in Participants With Active Uveitis Over Time	Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246	Corticosteroid doses were converted into prednisone equivalents. Participants with uveitis-related systemic corticosteroid that could not be converted to prednisone equivalents were excluded. Individual mean daily doses were calculated within the respective visit windows. For Week 0, only uveitis-related systemic corticosteroids at Baseline (Day 1 for all participants) were considered. Baseline was defined as Week 0 for all participants.
Mean Daily Dose (mg) of Uveitis-related Systemic Corticosteroids in Participants With Inactive Uveitis Over Time	Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246	Corticosteroid doses were converted into prednisone equivalents. Participants with uveitis-related systemic corticosteroid that could not be converted to prednisone equivalents were excluded. Individual mean daily doses were calculated within the respective visit windows. For Week 0, only uveitis-related systemic corticosteroids at Baseline (Day 1 for all participants) were considered. Baseline was defined as Week 0 for all participants.
Percent Change in Mean Daily Dose of Uveitis-related Systemic Corticosteroids Relative to Week 0 in Participants With Inactive Uveitis Using Systemic Corticosteroids at Week 0 Over Time	Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, and 198	Corticosteroid doses were converted into prednisone equivalents. Participants with uveitis-related systemic corticosteroid that could not be converted to prednisone equivalents were excluded. Individual mean daily doses were calculated within the respective visit windows. For Week 0, only uveitis-related systemic corticosteroids at Baseline (Day 1 for all participants) were considered. Baseline was defined as Week 0 for all participants. Data not presented after Week 198 as no participants remained on study as of Week 198.
Percent Change in Mean Daily Dose of Uveitis-related Systemic Corticosteroids Relative to Week 0 in Participants With Active Uveitis Using Systemic Corticosteroids at Week 0 Over Time	Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246	Corticosteroid doses were converted into prednisone equivalents. Participants with uveitis-related systemic corticosteroid that could not be converted to prednisone equivalents were excluded. Individual mean daily doses were calculated within the respective visit windows. For Week 0, only uveitis-related systemic corticosteroids at Baseline (Day 1 for all participants) were considered. Baseline was defined as Week 0 for all participants.
Percentage of Participants Not Using Systemic Corticosteroids Over Time	Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246	Corticosteroid doses were converted into prednisone equivalents. Participants with uveitis-related systemic corticosteroid that could not be converted to prednisone equivalents were excluded. Individual mean daily doses were calculated within the respective visit windows. For Week 0, only uveitis-related systemic corticosteroids at Baseline (Day 1 for all participants) were considered. Baseline was defined as Week 0 for all participants. Data presented for participants not using systemic corticosteroids at each timepoint.
Percentage of Participants Without Worsening of Best Corrected Visual Acuity (BCVA) by ≥15 Letters on Early Treatment Diabetic Retinopathy Study (ETDRS) in Both Eyes Relative to Baseline Over Time Among Participants Who Had Inactive Uveitis at Study Entry	Weeks 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246	Percentage of participants at each study time point without a worsening of Best Corrected Visual Acuity (BCVA) by ≥15 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) in both eyes relative to Baseline for participants who had inactive uveitis when they entered the study.
Percentage of Participants Without Worsening of BCVA by ≥15 Letters on the ETDRS in Both Eyes Relative to Week 8 Over Time Among Participants With Active Uveitis at Study Entry	Weeks 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246	Percentage of participants at each study time point without a worsening of BCVA by ≥15 letters on the ETDRS in both eyes relative to Week 8 for participant who had active uveitis when they entered the study.
Mean of Both Eyes of the Logarithm of the Minimum Angle of Resolution (LogMAR) BCVA Over Time	Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246	Using corrective lenses based on that visit's refraction testing, participant's BCVA was measured using an ETDRS logMAR chart. On the logMAR scale, 0 is equivalent to 20/20 visual acuity, the range of normal vision is considered to be from -0.2 to 0.1; higher values indicate visual impairment. Data presented includes the mean of both eyes for all participants (active or inactive uveitis) for all study time points.