Treatment of inflammation inside the eye caused by an overactive immune system (autoimmune uveitis) using adalimumab

The ASTUTE trial: Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness: a randomized controlled trial

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN31474800

Enrollment

174

Registered

2020-04-14

Start date

2020-12-01

Completion date

Unknown

Last updated

2026-05-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Autoimmune non-infectious uveitis Eye Diseases Autoimmune non-infectious uveitis

Interventions

Current interventions as of 25/03/2025: All participants start on open-label adalimumab for 16 weeks. Participants who respond to adalimumab are randomised to adalimumab or placebo for up to 128 week

Eligibility

Sex/Gender

All

Age

18 Years to 100 Years

Inclusion criteria

Inclusion criteria: Current inclusion criteria as of 21/11/2023: 1. Aged 18 years or over 2. Participant has: 2.1. Active sight-threatening ANIU (active inflammatory chorioretinal lesions OR abnormal central macular thickness (CMT) OR evidence of retinal vasculitis OR vitreous haze >0.5) and is being prescribed (already taking or being started on, if newly presenting with ANIU) oral prednisolone >5.0 mg/day; OR 2.2. Has controlled ANIU and is being prescribed oral prednisolone >5.0 mg/day. 3. Women must have a negative pregnancy test and be willing to use effective contraception for the duration of the participation in the trial and for 5 months after, or be surgically sterile or post-menopausal for >12 months 4. Able to provide informed consent Previous inclusion criteria: 1. Aged 18 years or over 2. Sight-threatening ANIU and is prescribed CS greater than 5.0 mg/day 3. Women must have a negative pregnancy test and be willing to use effective contraception for the duration of the participation in the trial and for 5 months after, or be surgically sterile or post-menopausal for >12 months 4. Able to provide informed consent

Exclusion criteria

Exclusion criteria: Current participant exclusion criteria as of 06/07/2022: 1. Participant has controlled ANIU and is maintained on oral prednisolone =5.0mg/day at the time of screening 2. Participant has systemic disease (whether associated with ANIU or not) that is being treated with steroids and requires >5mg/day oral prednisolone 3. Participant has untreated or active tuberculosis 4. Participant has severe infection, sepsis, or opportunistic infection 5. Participant has uncontrolled glaucoma 6. Participant has multiple sclerosis 7. Participant is HIV positive 8. Participant has hepatitis B or hepatitis C 9. Participant has syphilis 10. Participant has Lyme disease 11. Participant has Behcet’s disease 12. Participant has toxoplasmosis chorioretinitis 13. Participant has heart failure (NYHA III/IV) 14. Participant has been diagnosed with cancer <5 years ago 15. Participant is undergoing monitoring for recurrence of cancer/tumour growth where their oncologist has concern that a TNFalpha inhibitor would be contraindicated 16. Participant is taking another biologic drug 17. Participant has taken an anti-TNF drug within the previous 90 days (anakinra and abatacept are contraindicated); 18. Participant has had an Iluvien® implant within the previous 18 months and has controlled ANIU, or has had an Iluvien® implant within the previous 12 weeks regardless of whether ANIU is active or controlled 19. Participant has had an Ozurdex® implant, or an intravitreal steroid injection, or periocular steroid within the previous 12 weeks regardless of whether ANIU is active or controlled 20. Participant is pregnant 21. Participant has a known allergy or hypersensitivity to adalimumab or any of its excipients 22. Participant is taking part in another interventional study 23. Participant has an epiretinal membrane likely to prevent an eye meeting response criterion at 16 weeks of central macular thickness <320um Previous exclusion criteria as of 08/06/2020: 1. Participant has controlled ANIU and is maintained on CS =5.0mg/day at the time of screening 2. Participant has untreated or active tuberculosis 3. Participant has severe infection, sepsis or opportunistic infection 4. Participant has uncontrolled glaucoma 5. Participant has multiple sclerosis 6. Participant is HIV positive 7. Participant has hepatitis B or hepatitis C 8. Participant has syphilis 9. Participant has Lyme disease 10. Participant has Behcet's disease 11. Participant has heart failure (NYHA III/IV; 12. Participant has been diagnosed with cancer <5 years ago 13. Participant is undergoing monitoring for recurrence of cancer/tumour growth where their oncologist has concern that a TNFalpha inhibitor would be contraindicated 14. Participant is taking another biologic drug 15. Participant has taken an anti-TNF drug within the previous 90 days (anakinra and abatacept are contraindicated) 16. Participant has an ocular CS implant within the previous 12 months or an intravitreal steroid injection within the previous 3 months 17. Participant is pregnant 18. Participant has a known allergy or hypersensitivity to adalimumab or any of its excipients 19. Participant is taking part in another interventional study _____ Previous exclusion criteria: 1. Controlled ANIU and is maintained on CS less than or equal to 5.0 mg/day at the time of screening 2. Untreated or active tuberculosis 3. Severe infection, sepsis or opportunistic infection 4. Uncontrolled glaucoma 5. Multiple sclerosis 6. HIV positive 7. Hepatitis

Design outcomes

Primary

Measure	Time frame
Current primary outcome measure as of 25/03/2025: Time to the first treatment failure (TF) assessed at each visit after randomisation (12 weeks, 24 weeks, 36 weeks, 48 weeks, 64 weeks, 80 weeks, 96 weeks, 112 weeks, 128 weeks, 144 weeks and 160 weeks) i.e. TF may occur in either eye and may be triggered by incident ANIU in an eye that did not previously have ANIU. TF is defined as a composite of standard criteria reflecting clinical decision-making, including visual acuity and clinical signs of active inflammation, which have been used successfully in other ANIU trials. Participants will be assessed for TF at each visit after randomisation. Any of the following criteria in one or both eyes, where applicable, will constitute TF: 1. greater than or equal to 15 letter decrease in best-corrected visual acuity (BCVA), compared to BCVA measured by an optometrist masked to treatment allocation at the 16-week treatment run-in (TRI) visit 2. new active inflammatory chorioretinal lesions 3. greater than 20% increase in central macular thickness (CMT), compared to CMT at the 16-week TRI timepoint 4. onset or worsening of retinal vasculitis 5. 2-step worsening of vitreous haze cf. compared to best score at either the 8- or 16-week TRI visit vi. prescription by a masked clinician of greater than 5mg/day corticosteroids to maintain disease remission (i.e. to avert relapse before any of the above criteria for manifest active disease (i-v)) Previous primary outcome measures: Time to the first treatment failure (TF) assessed at each visit after randomisation (12 weeks, 24 weeks, 36 weeks, 48 weeks, 64 weeks, 80 weeks, 96 weeks, 112 weeks, and 128 weeks) i.e. TF may occur in either eye and may be triggered by incident ANIU in an eye that did not previously have ANIU. TF is defined as a composite of standard criteria reflecting clinical decision-making, including visual acuity and clinical signs of active inflammation, which have been used successfully in other ANIU trials. Partici	—

Measure

Time frame

Current primary outcome measure as of 25/03/2025: Time to the first treatment failure (TF) assessed at each visit after randomisation (12 weeks, 24 weeks, 36 weeks, 48 weeks, 64 weeks, 80 weeks, 96 weeks, 112 weeks, 128 weeks, 144 weeks and 160 weeks) i.e. TF may occur in either eye and may be triggered by incident ANIU in an eye that did not previously have ANIU. TF is defined as a composite of standard criteria reflecting clinical decision-making, including visual acuity and clinical signs of active inflammation, which have been used successfully in other ANIU trials. Participants will be assessed for TF at each visit after randomisation. Any of the following criteria in one or both eyes, where applicable, will constitute TF: 1. greater than or equal to 15 letter decrease in best-corrected visual acuity (BCVA), compared to BCVA measured by an optometrist masked to treatment allocation at the 16-week treatment run-in (TRI) visit 2. new active inflammatory chorioretinal lesions 3. greater than 20% increase in central macular thickness (CMT), compared to CMT at the 16-week TRI timepoint 4. onset or worsening of retinal vasculitis 5. 2-step worsening of vitreous haze cf. compared to best score at either the 8- or 16-week TRI visit vi. prescription by a masked clinician of greater than 5mg/day corticosteroids to maintain disease remission (i.e. to avert relapse before any of the above criteria for manifest active disease (i-v)) Previous primary outcome measures: Time to the first treatment failure (TF) assessed at each visit after randomisation (12 weeks, 24 weeks, 36 weeks, 48 weeks, 64 weeks, 80 weeks, 96 weeks, 112 weeks, and 128 weeks) i.e. TF may occur in either eye and may be triggered by incident ANIU in an eye that did not previously have ANIU. TF is defined as a composite of standard criteria reflecting clinical decision-making, including visual acuity and clinical signs of active inflammation, which have been used successfully in other ANIU trials. Partici

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Secondary

Measure	Time frame
Current primary outcome measure as of 25/03/2025: At 12 weeks, 24 weeks, 36 weeks, 48 weeks, 64 weeks, 80 weeks, 96 weeks, 112 weeks, 128 weeks, 144 weeks and 160 weeks, unless otherwise noted. 1. Individual treatment failure (TF) components, assessed at each trial visit 2. Retinal morphology (OCT; macular and retinal nerve fibre layer), assessed at each trial visit 3. Adverse events, assessed at each trial visit 4. Health-related quality of life measured using the EQ-5D-5L questionnaire at the start of treatment run-in (TRI), at 16 weeks immediately before randomisation, then 12-weekly after randomisation up to week 48 and 16-weekly thereafter 5. Patient-reported symptoms of side-effects at each trial visit after starting the TRI and at any interim attendance prompted by an adverse event 6. Patient-reported visual function at the start of TRI, at 16 weeks immediately before randomisation, 12-weekly up to week 48 and 16 weekly thereafter 7. Best corrected visual acuity (BCVA) assessed at each trial visit 8. Employment status at the start of TRI, at 16 weeks immediately before randomisation, 12-weekly up to week 48 and 16 weekly thereafter 9. Resource use during follow-up after randomisation, at the start of TRI, at 16 weeks immediately before randomisation, 12-weekly up to week 48 and 16 weekly thereafter Previous secondary outcome measures as of 13/12/2023 to 25/03/2025: At 12 weeks, 24 weeks, 36 weeks, 48 weeks, 64 weeks, 80 weeks, 96 weeks, 112 weeks, and 128 weeks unless otherwise noted. 1. Individual treatment failure (TF) components, assessed at each trial visit 2. Retinal morphology (OCT; macular and retinal nerve fibre layer), assessed at each trial visit 3. Adverse events, assessed at each trial visit 4. Health-related quality of life measured using the EQ-5D-5L questionnaire at the start of treatment run-in (TRI), at 16 weeks immediately before randomisation, then 12-weekly after randomisation up to week 48 and 16-weekly thereafter 5. Patient-reported sy	—

Measure

Time frame

Current primary outcome measure as of 25/03/2025: At 12 weeks, 24 weeks, 36 weeks, 48 weeks, 64 weeks, 80 weeks, 96 weeks, 112 weeks, 128 weeks, 144 weeks and 160 weeks, unless otherwise noted. 1. Individual treatment failure (TF) components, assessed at each trial visit 2. Retinal morphology (OCT; macular and retinal nerve fibre layer), assessed at each trial visit 3. Adverse events, assessed at each trial visit 4. Health-related quality of life measured using the EQ-5D-5L questionnaire at the start of treatment run-in (TRI), at 16 weeks immediately before randomisation, then 12-weekly after randomisation up to week 48 and 16-weekly thereafter 5. Patient-reported symptoms of side-effects at each trial visit after starting the TRI and at any interim attendance prompted by an adverse event 6. Patient-reported visual function at the start of TRI, at 16 weeks immediately before randomisation, 12-weekly up to week 48 and 16 weekly thereafter 7. Best corrected visual acuity (BCVA) assessed at each trial visit 8. Employment status at the start of TRI, at 16 weeks immediately before randomisation, 12-weekly up to week 48 and 16 weekly thereafter 9. Resource use during follow-up after randomisation, at the start of TRI, at 16 weeks immediately before randomisation, 12-weekly up to week 48 and 16 weekly thereafter Previous secondary outcome measures as of 13/12/2023 to 25/03/2025: At 12 weeks, 24 weeks, 36 weeks, 48 weeks, 64 weeks, 80 weeks, 96 weeks, 112 weeks, and 128 weeks unless otherwise noted. 1. Individual treatment failure (TF) components, assessed at each trial visit 2. Retinal morphology (OCT; macular and retinal nerve fibre layer), assessed at each trial visit 3. Adverse events, assessed at each trial visit 4. Health-related quality of life measured using the EQ-5D-5L questionnaire at the start of treatment run-in (TRI), at 16 weeks immediately before randomisation, then 12-weekly after randomisation up to week 48 and 16-weekly thereafter 5. Patient-reported sy

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Countries

England, United Kingdom

Contacts

Public ContactKirsty Lanyon

astute-trial@bristol.ac.uk+44 (0)117 455 1343

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: May 16, 2026