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UveitisPhase 2RUBINCT02929251

Randomized Trial Comparing Efficacy of Adalimumab, Anakinra and Tocilizumab in Non-infectious Refractory Uveitis

A Phase 2 study testing Anakinra, Tocilizumab and Adalimumab in people with Uveitis and Biotherapy, run by Assistance Publique - Hôpitaux de Paris at 27 sites in France.

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

RUBI, is the first prospective randomized, head to head study, comparing Adalimumab to either anakinra, or tocilizumab in refractory Non Infectious Uveitis (NIU). There is no firm evidence or randomized controlled trials directly addressing the best biologic agent in severe and refractory NIU. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Uveitis, Biotherapy
What is being tested?
Anakinra, Tocilizumab and Adalimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
112 participants
Where
27 sitesFrance
Study dates
29 Jun 2017to 29 Jan 2022
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Provide written, informed consent prior to the performance of any study specific procedures
  • Diagnosis of non-infectious intermediate, posterior-, or pan-uveitis in at least one eye fulfilling the International Study Group Classification Criteria (Standardization of Uveitis Nomenclature [SUN] criteria) of posterior, or pan- uveitis confirmed by documented medical history
  • Currently uncontrolled uveitic disease. Uncontrolled uveitic disease is defined as fulfilling one of the two following criteria at Inclusion:
  • Active inflammatory chorioretinal and/or inflammatory retinal vascular lesions and/or macular edema (CRT ≥300 microns) OR
  • Vitreous haze grade ≥4 on the Miami 9-step scale (or VH >1+ according to SUN/NEI classification)
  • a. Patient who are receiving prednisone ≥10 mg/day and <80mg/day (or equivalent dose of another corticosteroid) at stable dose 30 days prior to the first study drug administration on Day 0 and who received at least 1 other systemic immunosuppressant (All systemic immunosuppressants must have been discontinued 30 days prior to the first study drug administration on Day 0), or, b. Patient who received IFN alpha (All systemic immunosuppressants must have been discontinued 30 days prior to the first study drug administration on Day 0), or, c. To be intolerant to immunosuppressant
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  • Best corrected visual acuity (BCVA) by ETDRS ≥ to 20/400 in either eye
  • Stable dose for two weeks prior to inclusion of topical corticosteroids and/or NSAIDs
  • Male or female , Age >= 18 years at Inclusion
  • Weight 40 - 120 kg (88.2 - 264 lbs) at Inclusion
  • Chest X-ray or thoracic CT scan results (postero-anterior and lateral) within 12 weeks prior to Inclusion with no evidence of active Tuberculosis, active infection, or malignancy
  • For female subjects of child-bearing age, a negative serum or urine pregnancy test
  • For subjects with reproductive potential, a willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study and 3 and 5 months after stopping therapy for roactemra and adalimumab, respectively. Birth control methods which may be considered as highly effective methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods (according to CTFG recommendations). Such methods include :
  • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation 1:
  • oral
  • intravaginal
  • transdermal
  • progestogen-only hormonal contraception associated with inhibition of ovulation 1:
  • oral
  • injectable
  • implantable
  • intrauterine device (IUD)
  • intrauterine hormone-releasing system ( IUS)
  • bilateral tubal occlusion
  • vasectomised partner
  • sexual abstinence (In the context of this guidance sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject).
  • A QuantiFERON®-Tuberculosis (TB) test within 6 months prior to Screening

Who cannot join

  • Infectious uveitis, masquerade syndromes (idiopathic uveitis is permitted)
  • Isolated anterior uveitis
  • Presence of cataract or posterior capsular opacification so severe that an assessment of the posterior segment of either eye is inadequate or impossible
  • Contraindication to mydriasis in either eye or presence of posterior synechiae in the study eye such that mydriasis is inadequate for posterior segment examination
  • Intraocular pressure ≥ 25 mmHg by Goldmann tonometry or advanced glaucoma in either eye
  • Monocular patient
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  • Active tuberculosis
  • Known positive syphilis serology, HIV antibody, hepatitis B surface antigen and/or anti-nucleocapsid antibody of hepatitis B virus and/or Hepatitis C virus, within 1 month prior to inclusion.
  • History of malignancy within 5 years prior to Inclusion other than carcinoma in situ of the cervix or adequately treated, non-metastatic squamous or basal cell carcinoma of the skin.
  • History of severe allergic or anaphylactic reactions to monoclonal antibodies
  • Infectious disease:
  • Fever or infection requiring treatment with antibiotics within 3 weeks prior to Inclusion
  • History of recurrent infection or predisposition to infection
  • Known immunodeficiency
  • History of multiple sclerosis and/or demyelinating disorder
  • Laboratory values assessed during Inclusion:
  • Hemoglobin < 8g/dL
  • White Blood Cell Count (WBC) < 2.0 x 10^3/mm3
  • Platelet count < 80 x 10^3/mm3
  • Glomerular filtration rates (GFR) <30ml/min.
  • Transaminases > 3 times upper normal value
  • Use of the following systemic treatments during the specified periods:
  • Any other previous systemic biologic therapy
  • Treatment with any systemic alkylating agents within 12 months prior to Inclusion or between Inclusion and Day 0 (e.g., cyclophosphamide, chlorambucil)
  • Any live (attenuated) vaccine within 3 months prior to Inclusion
  • Use of the following ocular treatments during the specified periods:
  • Previous anti Vascular Endothelial Growth Factor (VEGF) intravitreal therapy (applied to both eyes) within 3 months prior to Inclusion, or anticipated use during the study period
  • Treatment with dexamethasone intravitreal implant [Ozurdex®]) within 6 months prior to Inclusion
  • Intravitreal corticosteroids within 3 months prior to Inclusion. Previous Subtenon's corticosteroid injections are permitted if administered at least 2 months prior to Inclusion
  • Stage III and IV New York Heart Association (NYHA) cardiac insufficiency

Trial locations and contacts

27 sites in 1 country.

27 sites in 1 country

France27 sites

  • Hopital Avicenne - CRC

    Bobigny

  • Hopital Avicenne - Ophtalmologie

    Bobigny

  • Hopital Avicenne- Médecine interne

    Bobigny

  • Hopital Pellegrin

    Bordeaux

  • Hopital Saint André - Médecine interne

    Bordeaux

  • CHU Clermont-Ferrand - Hopital Gabriel Montpied - Médecine interne

    Clermont-Ferrand

  • CHU Clermont-Ferrand - Hopital Gabriel Montpied - Ophtalmologie

    Clermont-Ferrand

  • CHU Dijon Bourgogne -Ophtalmologie

    Dijon

  • CHU Dijon Bourgogne Médecine Interne et Maladies Systémiques - Médecine 2 / SOC 2

    Dijon

  • HCL - Hôpital de la Croix Rousse - Médecine interne

    Lyon

  • HCL - Hôpital de la Croix Rousse - Ophtalmologie

    Lyon

  • CHRU de Nancy - Médecine interne

    Nancy

  • CHRU de Nancy

    Nancy

  • Hopital la pitié salpetriere - Médecine interne 1

    Paris, paris, 75013

  • CHNO des Quinze Vingt - Médecine interne

    Paris

  • CHNO des Quinze Vingt - Ophtalmologie

    Paris

  • CHNO des Quinze Vingt

    Paris

  • Hopital Pitié Salpetriere

    Paris

  • Hopital Rotchild - Médecine interne

    Paris

  • Hopital Rotchild - Ophtalmologie

    Paris

  • Hôpital de la pitié salpêtrière - Ophtalmologie

    Paris

  • CHRU de Rennes Hopital Sud Médecine interne

    Rennes

  • CHU Rennes - Hopital Ponchaillou - Ophtalmologie

    Rennes

  • CHU Rouen - Hopital Charles Nicolle - Ophtalmologie

    Rouen

  • CHU Rouen - Hopital Charles Nicolle - Médecine interne

    Rougé

  • CHU TOULOUSE - HOPITAL PIERRE PAUL RIQUET - Ophtalmologie

    Toulouse

  • CHU Toulouse - Hopital Rangueil

    Toulouse

Other trials in France

About this study

Official title: Multicentre, Randomized, Multi-arm Trial Comparing the Efficacy and Safety of Adalimumab, Anakinra and Tocilizumab in Subjects With Non-infectious Refractory Uveitis RUBI: Refractory Uveitis BIotherapies

RUBI, is the first prospective randomized, head to head study, comparing Adalimumab to either anakinra, or tocilizumab in refractory Non Infectious Uveitis (NIU). There is no firm evidence or randomized controlled trials directly addressing the best biologic agent in severe and refractory NIU. NIU can cause devastating visual loss and up to 20% of legal blindness. Corticosteroids and immunosuppressants failed to demonstrate sustainable remission over 70 % of refractory/relapsing severe uveitis. The incidence of blindness in NIU has been dramatically reduced in the recent years with the use of biologics, raising the question of whether these compounds should be used earlier in the treatment of severe non infectious uveitis. Contrasting with immunosuppressors, biotherapies act rapidly and are highly effective in steroid's sparing thus preventing occurrence of cataract and/or glaucoma.

Despite a strong rationale, these compounds are not yet approved in uveitis, which guarantees the innovative nature of this study that aims selecting or dropping any arm when evidence of efficacy already exists.

Conditions
Uveitis, Biotherapy
Being tested
Anakinra, Tocilizumab, Adalimumab
Medical subject headings
Uveitis

What participants receive

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

  • AnakinraDrug

    Anakinra (100 mg/day subcutaneously) (n=40) for 16 weeks

  • TocilizumabDrug

    Tocilizumab (162 mg/7 days subcutaneously) (n=40) for 16 weeks.

  • AdalimumabDrug

    Adalimumab (40mg/14 days subcutaneously) (n=40) for 16 weeks

Study groups in NCT02929251
Study groupRoleWhat they receive
AdalimumabActive comparatorAdalimumab (40mg/14 days subcutaneously) (n=40) for 16 weeks
Receives: Drug: Adalimumab
AnakinraExperimentalAnakinra (100 mg/day subcutaneously) (n=40) for 16 weeks
Receives: Drug: Anakinra
TocilizumabExperimentalTocilizumab (162 mg/7 days subcutaneously) (n=40) for 16 weeks.
Receives: Drug: Tocilizumab

What is being measured

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

  1. Percentage of patients with at least 2-step reduction in Vitreous Haze (according to Miami 9-step Scale) and with a dose <= 0.1 mg/Kg/day of prednisone (or equivalent oral corticosteroid)

    Percentage of patients with at least 2-step reduction in Vitreous Haze (according to Miami 9-step Scale) and with a dose <= 0.1 mg/Kg/day of prednisone (or equivalent oral corticosteroid)

    Measured: Week 16

Secondary outcomes (17)

  1. Mean change from baseline in Vitreous Haze

    Mean change from baseline in Vitreous Haze

    Measured: Week 4, 8, 12, 16, 24

  2. Percentage of patients with anterior chamber score = 0 or at least 2-step reduction in score (Tyndall and flare according to the Standardization of Uveitis Nomenclature (SUN) classification)

    Measured: Week 4, 8, 12, 16, 24

  3. Mean change from baseline in BCVA (ETDRS letters score)

    Measured: Week 4, 8, 12, 16, 24

  4. Mean change from baseline in central retinal thickness measured with Optical Coherence Tomography (OCT)

    Measured: Week 4, 8, 12, 16, 24

  5. Percentage of patients with Central Retinal Thickness (CRT) <300 microns

    Measured: Week 4, 8, 12, 16, 24

  6. Percentage of patients without retinal vessel leakage on fluorescein angiography

    Measured: Week 4, 8, 12, 16, 24

  7. Percent meeting targets ≤ 0.1 mg/day prednisone

    Measured: week 16

  8. Mean change in prednisone dose

    Measured: Week 4, 8, 12, 16, 24

  9. Mean dose of prednisone

    Measured: week 16

  10. Cumulative dose of prednisone

    Measured: week 16

  11. Time to response onset

    Measured: week 16

  12. Time to relapse of uveitis

    Measured: week 30

  13. Number of relapse of uveitis

    Measured: week 30

  14. Underlying systemic disease

    Complete remission of extra opthalmologic sign of Behcet disease or sarcoidosis

    Measured: week 4, 8, 12, 16, 24

  15. Percentage of adverse event

    Measured: week 4, 8, 12, 16, 24

  16. Percentage of serious adverse event

    Measured: week 4, 8, 12, 16, 24

  17. time to treatment failure

    Measured: week 30

Timeline

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

  1. First posted11 Oct 2016 (estimated)
  2. Study start29 Jun 2017
  3. Primary completion29 Oct 2021
  4. Study completion29 Jan 2022

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
112 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02929251
Sponsor's protocol ID
P150945
Other IDs
2016-002284-34, 2016
Acronym
RUBI
Status last verified
Jun 2024
First submitted
7 Oct 2016
Last updated
16 Sep 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Saadoun D, Ghembaza A, Touhami S, Girszyn N, Bielefeld P, Seve P, Pugnet G, Andre M, Leclercq M, Rogier T, Ribeiro E, Hie M, Clavel G, Abad S, Stanescu-Segall D, Toutee A, Gueudry J, Bron A, Kodjikian L, Soler V, Chiambaretta F, Sene T, Titah SMC, Heron E, Moulana A, Trad S, Terrada C, Massamba N, Raked N, Resche-Rigon M, Domont F, Desbois AC, Maalouf G, Vautier M, Cacoub P, Desseaux K, Vieira M, Biard L, Bodaghi B. Adalimumab, Anakinra, and Tocilizumab in Patients With Noninfectious Uveitis: A Multicenter Randomized Controlled Trial. Am J Ophthalmol. 2026 May;285:202-212. doi: 10.1016/j.ajo.2026.01.037. Epub 2026 Feb 3.

    PubMed 41643758

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anakinra, Tocilizumab and Adalimumab in people with Uveitis and Biotherapy, run by Assistance Publique - Hôpitaux de Paris at 27 sites in France.

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 27 inclusion and 30 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 16 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Percentage of patients with at least 2-step reduction in Vitreous Haze (according to Miami 9-step Scale) and with a dose <= 0.1 mg/Kg/day of prednisone (or equivalent oral corticosteroid) (time frame: Week 16). 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 NCT02929251, 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 16 Sep 2025.

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