Clinical trial NCT01148225: A Study of the Long-term Safety and Efficacy of Adalimumab in Subjects With Intermediate-, Posterior-, or Pan-uveitis
Official title: A Multicenter Open-Label Study of the Long-term Safety and Efficacy of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects With Non-infectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Uveitis
Keywords: Intermediate-Uveitis
Non-infectious Uveitis
Posterior-Uveitis
Active Uveitis
Pan-uveitis
Uveitis
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2010-06-22
Enrollment: 424
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Baseline to Final Visit (up to 366 weeks)
measure: Hematology: Number of Participants With Potentially Clinically Significant (PCS) Values
timeFrame: Baseline to Final Visit (Up to 366 weeks)
measure: Chemistry: Number of Participants With PCS Values
timeFrame: Baseline to Final Visit (Up to 366 weeks)
measure: Pulse (Sitting): Mean Change (Beats Per Minute) From Baseline To Final Visit
timeFrame: Baseline to Final Visit (Up to 366 weeks)
measure: Respiratory Rate (Sitting): Mean Change (Respirations Per Minute) From Baseline To Final Visit
timeFrame: Baseline to Final Visit (Up to 366 weeks)
measure: Temperature (Sitting): Mean Change (Centigrade) From Baseline To Final Visit
timeFrame: Baseline to Final Visit (Up to 366 weeks)
measure: Diastolic and Systolic Blood Pressure (Sitting): Mean Change (mmHg) From Baseline To Final Visit
timeFrame: Baseline to Final Visit (Up to 366 weeks)
Secondary outcomes:
measure: Percentage of Participants in Quiescence Over Time
timeFrame: 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
measure: Percentage of Participants With Uveitis Flare Among Participants With Inactive Uveitis at Study Start
timeFrame: 366 Weeks
measure: Percentage of Participants With Uveitis Flare From Week 8 Through Last Visit Among Participants With Active Uveitis at Study Start
timeFrame: Weeks 8 to 246 (238 Weeks)
measure: 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
timeFrame: 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
measure: Percentage of Participants With Steroid-free Quiescence Over Time
timeFrame: 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
measure: 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
timeFrame: 366 Weeks
measure: 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
timeFrame: 366 Weeks
measure: Percentage of Participants Who Started Uveitis-related Systemic Corticosteroids During the Study
timeFrame: 366 Weeks
measure: Mean Daily Dose in Milligrams (mg) of Uveitis-related Systemic Corticosteroids in Participants With Active Uveitis Over Time
timeFrame: 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
measure: Mean Daily Dose (mg) of Uveitis-related Systemic Corticosteroids in Participants With Inactive Uveitis Over Time
timeFrame: 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
measure: 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
timeFrame: Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, and 198
measure: 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
timeFrame: 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
measure: Percentage of Participants Not Using Systemic Corticosteroids Over Time
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: Weeks 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246
measure: Mean of Both Eyes of the Logarithm of the Minimum Angle of Resolution (LogMAR) BCVA Over Time
timeFrame: 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
Other outcomes:
measure: Percent Change in Left Eye in Central Retinal Thickness (1 mm Subfield) From Baseline to Each Study Time Point Relative to Baseline for Participants Who Had Inactive Uveitis at Study Entry Over Time
timeFrame: Baseline (Week 0) and 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
measure: Percent Change in Right Eye in Central Retinal Thickness (1 mm Subfield) From Baseline to Each Study Time Point Relative to Baseline for Participants Who Had Inactive Uveitis at Study Entry Over Time
timeFrame: Baseline (Week 0) and 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
measure: Percent Change in Left Eye of Central Retinal Thickness (1 mm Subfield) at Each Study Time Point Relative to Week 8 for Participants Who Had Active Uveitis at Study Entry Over Time
timeFrame: Baseline (Week 8) and Weeks 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246
measure: Percent Change in Right Eye of Central Retinal Thickness (1 mm Subfield) at Each Study Time Point Relative to Week 8 for Participants Who Had Active Uveitis at Study Entry Over Time
timeFrame: Baseline (Week 8) and Weeks 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246
measure: Percentage of Participants With Grade ≤0.5+ in Anterior Chamber (AC) Cells in Both Eyes on Slit Lamp Exam According to Standardization of Uveitis Nomenclature (SUN) Criteria Over Time
timeFrame: 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
measure: Percentage of Participants Achieving a ≥50% Reduction in Immunosuppression Load Relative to Baseline Over Time Among Participants With Inactive Uveitis at Study Entry
timeFrame: Weeks 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, and 234
measure: Percentage of Participants Achieving a ≥50% Reduction in Immunosuppression Load Relative to Week 8 Over Time Among Participants With Active Uveitis at Study Entry
timeFrame: Weeks 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246
measure: Percentage of Participants With No New Active, Inflammatory Chorioretinal or Inflammatory Retinal Vascular Lesion in Both Eyes Relative to Baseline Over Time Among Participants With Inactive Uveitis at Study Entry
timeFrame: 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
measure: Percentage of Participants With No New Active, Inflammatory Chorioretinal or Inflammatory Retinal Vascular Lesion in Both Eyes Relative to Week 8 Over Time Among Participants With Active Uveitis at Study Entry
timeFrame: Weeks 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246
measure: Percentage of Participants With Grade ≤0.5+ in VH in Both Eyes on Indirect Ophthalmoscopy According to NEI/SUN Criteria Over Time
timeFrame: 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
measure: Change in National Eye Institute (NEI) Visual Functioning Questionnaire (VFQ-25) Score at Each Study Time Point Relative to Baseline for Participants Who Had Inactive Uveitis at Study Entry Over Time
timeFrame: Weeks 0, 8, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246
measure: Change in NEI VFQ-25 Score at Each Study Time Point Relative to Week 8 for Participants Who Had Active Uveitis at Study Entry Over Time
timeFrame: Weeks 0, 8, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246
Locations:
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: Suhler EB, Jaffe GJ, Fortin E, Lim LL, Merrill PT, Dick AD, Brezin AP, Nguyen QD, Thorne JE, Van Calster J, Cimino L, Adan A, Goto H, Kaburaki T, Kramer M, Vitale AT, Kron M, Song AP, Liu J, Pathai S, Douglas KM, Schlaen A, Muccioli C, Van Velthoven MEJ, Zierhut M, Rosenbaum JT. Long-Term Safety and Efficacy of Adalimumab in Patients with Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis. Ophthalmology. 2021 Jun;128(6):899-909. doi: 10.1016/j.ophtha.2020.10.036. Epub 2020 Nov 3.