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UveitisPhase 3VISUAL IIINCT01148225

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

A Phase 3 study testing adalimumab in people with Uveitis, run by AbbVie.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Uveitis
What is being tested?
adalimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
424 participants
Where
No sites listed yet
Study dates
23 Nov 2010to 21 May 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

About this study

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

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.

Read the 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.

Conditions
Uveitis
Being tested
adalimumab
Keywords
Intermediate-Uveitis, Non-infectious Uveitis, Posterior-Uveitis, Active Uveitis, Pan-uveitis, Uveitis
Medical subject headings
Uveitis, Uveitis, Intermediate, Uveitis, Posterior

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • adalimumabDrug

    Also called ABT-D2E7, Humira

    Adalimumab, pre-filled syringe, administered by SC injection

Study groups in NCT01148225
Study groupRoleWhat they receive
AdalimumabOtherParticipants received open label (OL) adalimumab 40 mg by subcutaneous (SC) injection every other week (eow) until the final visit.
Receives: Drug: adalimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Adverse Events

    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.

    Measured: Baseline to Final Visit (up to 366 weeks)

  2. Hematology: Number of Participants With Potentially Clinically Significant (PCS) Values

    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.

    Measured: Baseline to Final Visit (Up to 366 weeks)

  3. Chemistry: Number of Participants With PCS Values

    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.

    Measured: Baseline to Final Visit (Up to 366 weeks)

  4. Pulse (Sitting): Mean Change (Beats Per Minute) From Baseline To Final Visit

    Heart rate (beats per minute) was measured while the participant was sitting.

    Measured: Baseline to Final Visit (Up to 366 weeks)

  5. Respiratory Rate (Sitting): Mean Change (Respirations Per Minute) From Baseline To Final Visit

    Respiratory rate (respirations per minute) was measured while the participant was sitting.

    Measured: Baseline to Final Visit (Up to 366 weeks)

  6. Temperature (Sitting): Mean Change (Centigrade) From Baseline To Final Visit

    Temperature was measured while the participant was sitting.

    Measured: Baseline to Final Visit (Up to 366 weeks)

  7. Diastolic and Systolic Blood Pressure (Sitting): Mean Change (mmHg) From Baseline To Final Visit

    Blood pressure was measured while the participant was sitting. Abbreviations used include mmHg=millimeters of mercury.

    Measured: Baseline to Final Visit (Up to 366 weeks)

Secondary outcomes (16)
  1. Percentage of Participants in Quiescence Over Time

    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.

    Measured: 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

  2. Percentage of Participants With Uveitis Flare Among Participants With Inactive Uveitis at Study Start

    Uveitis flare is defined as no quiescence (active inflammatory lesions and AC cell grade > 0.5+ and/or VH grade >0.5+).

    Measured: 366 Weeks

  3. Percentage of Participants With Uveitis Flare From Week 8 Through Last Visit Among Participants With Active Uveitis at Study Start

    Uveitis flare is defined as no quiescence (active inflammatory lesions and AC cell grade > 0.5+ and/or VH grade >0.5+).

    Measured: Weeks 8 to 246 (238 Weeks)

  4. 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

    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.

    Measured: 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

  5. Percentage of Participants With Steroid-free Quiescence Over Time

    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.

    Measured: 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

  6. 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

    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.

    Measured: 366 Weeks

  7. 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

    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.

    Measured: 366 Weeks

  8. Percentage of Participants Who Started Uveitis-related Systemic Corticosteroids During the Study

    Percentage of participants who started uveitis-related systemic corticosteroids during the study.

    Measured: 366 Weeks

  9. Mean Daily Dose in Milligrams (mg) of Uveitis-related Systemic Corticosteroids in Participants With Active Uveitis Over Time

    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.

    Measured: 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

  10. Mean Daily Dose (mg) of Uveitis-related Systemic Corticosteroids in Participants With Inactive Uveitis Over Time

    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.

    Measured: 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

  11. 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

    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.

    Measured: Weeks 0, 2, 4, 8, 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, and 198

  12. 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

    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.

    Measured: 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

  13. Percentage of Participants Not Using Systemic Corticosteroids Over Time

    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.

    Measured: 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

  14. 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

    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.

    Measured: 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

  15. 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

    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.

    Measured: Weeks 12, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 222, 234, and 246

  16. Mean of Both Eyes of the Logarithm of the Minimum Angle of Resolution (LogMAR) BCVA Over Time

    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.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jun 2010 (estimated)
  2. Study start23 Nov 2010
  3. Primary completion21 May 2018
  4. Study completion21 May 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
424 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01148225
Sponsor's protocol ID
M11-327
Other IDs
2009-016196-29, 2009
Acronym
VISUAL III
Status last verified
Jul 2021
First submitted
14 May 2010
Last updated
12 Jul 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 33157077

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing adalimumab in people with Uveitis, run by AbbVie.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events (time frame: Baseline to Final Visit (up to 366 weeks)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01148225, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2021.

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