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

NCT02929251 | Completed Phase 2 DMC

• 2 other identifiers: P1509452016-002284-34
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 27

Brief 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. 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

Outcome Measures

Primary Outcomes (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)

  Week 16

Secondary Outcomes (17)

• Mean change from baseline in Vitreous Haze

  Week 4, 8, 12, 16, 24

• 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)

  Week 4, 8, 12, 16, 24

• Mean change from baseline in BCVA (ETDRS letters score)

  Week 4, 8, 12, 16, 24

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

  Week 4, 8, 12, 16, 24

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

  Week 4, 8, 12, 16, 24

Study Arms (3)

Adalimumab

ACTIVE COMPARATOR

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

Drug: Adalimumab

Anakinra

EXPERIMENTAL

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

Drug: Anakinra

Tocilizumab

EXPERIMENTAL

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

Drug: Tocilizumab

Interventions

Anakinra DRUG

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

Anakinra

Tocilizumab DRUG

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

Tocilizumab

Adalimumab DRUG

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

Adalimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• Best corrected visual acuity (BCVA) by ETDRS ≥ to 20/400 in either eye
• 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

You may not qualify if:

• 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
• Active tuberculosis
• History of severe allergic or anaphylactic reactions to monoclonal antibodies
• Infectious disease:
• History of recurrent infection or predisposition to infection
• Known immunodeficiency
• History of multiple sclerosis and/or demyelinating disorder
• Hemoglobin \< 8g/dL
• White Blood Cell Count (WBC) \< 2.0 x 10\^3/mm3
• Platelet count \< 80 x 10\^3/mm3

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (27)

Hopital la pitié salpetriere - Médecine interne 1

Paris, paris, 75013, France

Location

Hopital Avicenne - CRC

Bobigny, France

Location

Hopital Avicenne - Ophtalmologie

Bobigny, France

Location

Hopital Avicenne- Médecine interne

Bobigny, France

Location

Hopital Pellegrin

Bordeaux, France

Location

Hopital Saint André - Médecine interne

Bordeaux, France

Location

CHU Clermont-Ferrand - Hopital Gabriel Montpied - Médecine interne

Clermont-Ferrand, France

Location

CHU Clermont-Ferrand - Hopital Gabriel Montpied - Ophtalmologie

Clermont-Ferrand, France

Location

CHU Dijon Bourgogne -Ophtalmologie

Dijon, France

Location

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

Dijon, France

Location

HCL - Hôpital de la Croix Rousse - Médecine interne

Lyon, France

Location

HCL - Hôpital de la Croix Rousse - Ophtalmologie

Lyon, France

Location

CHRU de Nancy - Médecine interne

Nancy, France

Location

CHRU de Nancy

Nancy, France

Location

CHNO des Quinze Vingt - Médecine interne

Paris, France

Location

CHNO des Quinze Vingt - Ophtalmologie

Paris, France

Location

CHNO des Quinze Vingt

Paris, France

Location

Hopital Pitié Salpetriere

Paris, France

Location

Hopital Rotchild - Médecine interne

Paris, France

Location

Hopital Rotchild - Ophtalmologie

Paris, France

Location

Hôpital de la pitié salpêtrière - Ophtalmologie

Paris, France

Location

CHRU de Rennes Hopital Sud Médecine interne

Rennes, France

Location

CHU Rennes - Hopital Ponchaillou - Ophtalmologie

Rennes, France

Location

CHU Rouen - Hopital Charles Nicolle - Ophtalmologie

Rouen, France

Location

CHU Rouen - Hopital Charles Nicolle - Médecine interne

Rougé, France

Location

CHU TOULOUSE - HOPITAL PIERRE PAUL RIQUET - Ophtalmologie

Toulouse, France

Location

CHU Toulouse - Hopital Rangueil

Toulouse, France

Location

MeSH Terms

Conditions

Uveitis

Interventions

Interleukin 1 Receptor Antagonist Protein; tocilizumab; Adalimumab

Condition Hierarchy (Ancestors)

Uveal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Study Officials

• David Saadoun, MD PHD

  APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2016
• First Posted: October 11, 2016
• Study Start: June 29, 2017
• Primary Completion: October 29, 2021
• Study Completion: January 29, 2022
• Last Updated: September 16, 2025

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (27)