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UveitisPhase 3Co-THEIANCT04798755

Efficacy, Safety and Costs of Methotrexate, Adalimumab, or Their Combination in Non-infectious Non-anterior Uveitis

A Phase 3 study testing Methotrexate, Adalimumab and Adalimumab+Methotrexate in people with Uveitis, run by Hospital San Carlos, Madrid at 14 sites in Spain.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Introduction: Non-infectious uveitis (NIUs) include a heterogeneous group of sight-threatening conditions. NIUs can be highly disabling and be associated with a profound impact in the quality-of-life (QoL) and wellbeing. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Uveitis
What is being tested?
Methotrexate, Adalimumab and Adalimumab+Methotrexate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
192 participants
Where
14 sitesSpain
Study dates
12 Jan 2022to 1 Oct 2025
Phase
Phase 3
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

  • Subjects diagnosed with non-infectious intermediate-, posterior-, or pan-uveitis in at least one eye;
  • Adult patients (≥18 years);
  • Subjects with at least one flare of active eye inflammation in the previous 180 days before Baseline visit, defined by the presence of at least 1 of the following parameters in either eye:
  • Active chorioretinal or retinal vascular lesion, AND/OR
  • Presence of macular edema by optical coherence tomography (OCT:thickness >350 μm AND cysts or intraretinal fluid), AND/OR
  • ≥ 2+ anterior chamber cells (ACC; SUN criteria4) , AND/OR
Show all 25Show fewer
  • ≥ 2+ vitreous haze (National Eye Institute [NEI]113/SUN criteria4).
  • Subjects with active eye inflammation at Baseline visit, defined by the presence of at least 1 of the following parameters in either eye:
  • Active chorioretinal or retinal vascular lesion, AND/OR
  • Presence of macular edema by OCT (thickness >350 μm AND cysts or intraretinal fluid), AND/OR
  • ≥ 1+ ACC, AND/OR
  • ≥ 1+ vitreous haze.
  • Subjects meeting at least ONE of the following criteria:
  • Subjects with known chronic condition necessitating GCs-sparing immunosuppressive treatment: Behçet's disease with posterior segment involvement, multifocal choroiditis with panuveitis, serpiginous choroidopathy, birdshot retinochoroidopathy, diffuse retinal vasculitis, Vogt-Koyanagi-Harada with bullous serous retinal and/or choroidal detachments, sympathetic ophthalmia. No prior therapy is required for these patients. AND/OR
  • Subjects with registered local/systemic corticosteroid refractory uveitis in the previous 180 months before Baseline visit, defined as:
  • Presence of active inflammation after 4 weeks of high-dose (1mg/kg prednisone equivalent) corticosteroid treatment, resulting in an incomplete response (there was an amelioration, but there is still inflammation); AND/OR, Presence of active inflammation 4 weeks after a regional corticosteroid injection; AND/OR,
  • Treatment with oral corticosteroids resulting in a reduction of inflammation, followed by relapse [increase in ≥1 grade in ACC or vitreous haze or a change of non-active to active lesions (including chorioretinal or retinal vascular lesion and/or macular edema)] when GCs was tapered; AND/OR,
  • Presence of active inflammation after a long-acting corticosteroid intramuscular injection administered between 4 weeks to 180 days before the Baseline visit); AND/OR, Active inflammation after treatment with >10mg/day oral prednisone for at least the past 90 days before Baseline.
  • If female, subject is:
  • Not of childbearing potential: at least 1 year or more since the final menstrual period or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy);
  • Of childbearing potential and willing to use an acceptable method of contraception during the study period (i.e. pharmacologics, devices, barrier methods) or abstinence, and for 150 days after the last dose of study drugs;
  • Not pregnant or breastfeeding
  • Subject has a negative tuberculosis skin test (PPD test or equivalent) and nonpathological Chest X-ray (CXR; Posterior-anterior and lateral view) at Screening or in the previous 90 days before Baseline visit. If the subject has a positive PPD test (or equivalent), has had a past ulcerative reaction to PPD placement and/or a CXR consistent with prior tuberculosis (TB) exposure, the subject must initiate, be currently receiving or have documented completion of a course of prophylactic anti-TB therapy
  • Subjects able and willing to provide written informed consent and to comply with the study protocol.
  • Do not participate in another clinical trial.

Who cannot join

  • Subjects with confirmed or suspected infectious uveitis, including ocular histoplasmosis syndrome
  • Subjects with previous intolerability, safety issues according to investigator criteria, AND/OR previous failure to control ocular or other inflammation with MTX
  • Subjects with previous exposure to any biological therapy at any time (excluding intravitreal anti-vascular endothelial growth factor [anti-VEGF] therapy and denosumab), including those with that have a potential or known association with progressive multifocal leukoencephalopathy (i.e. natalizumab, rituximab or efalizumab);
  • Subjects with previous exposure to synthetic immunosuppressive therapy (such as mycophenolate or cyclosporine) other than corticosteroids in the past 6 months before Baseline;
  • Subjects with chronic structural eye damage considered by the Site's
  • Investigator to:
  • Interfere with the measurement of any of the study outcomes, AND/OR b. Cause eye damage regardless of the inflammatory process, AND/OR c. Prevent the normalization of the eye structures; 6. Chronic hypotony (IOP < 5 mm Hg for in the last 3 months and/or in the baseline visit) in both eyes; 7. Subjects receiving local GCs 8. Subjects receiving intravitreal anti-VEGF therapy 9. Subjects with a history of prior intraocular surgery within 30 days prior to the Baseline visit, AND/OR any planned eye surgery within the next 52 weeks from Baseline Visit 10. Subjects with best spectacle-corrected visual acuity (BCVA) worse than 20/400 (ETDRS logMAR > 1.34) in the better eye during the screening or at Baseline visit 11. Subjects with active malignancy considered by the Site's Investigator, including lymphoma, leukemia, non-melanoma skin cancer, and confirmed or suspected ocular masquerade syndromes 12. Subjects with systemic autoimmune disease or ocular condition (besides uveitis) anticipated to dictate treatment course, as considered by the Site's Investigator 14. Subjects with systemic active or chronic recurring infections, such as active TB, syphilis, or hepatitis B or C, at Screening visit or in the previous 90 days before Baseline visit; AND/OR a history of invasive infection (e.g., listeriosisand histoplasmosis); 15. Subjects with history of moderate to severe congestive heart failure (NYHA class III or IV), recent cerebrovascular accident (6 months) and any other condition which, in the opinion of the Site's Investigator, would put the subject at risk by participation in the study 16. Subjects with clinically significant abnormal screening laboratory results as evaluated by the Site's Investigator (at screening/baseline or in the previous4 weeks).
  • 17. Central nervous system demyelinating disease

Trial locations and contacts

14 sites in 1 country.

Luis Rodriguez Rodriguez contact

+0034-91330300 ext. 7560

lrrodriguez@salud.madrid.org

14 sites in 1 country

Spain14 sites, 14 recruiting

  • Complejo Hospitalario Universitario A Coruña

    A Coruña

    JOSE A PINTO TASENDE

    Not yet recruiting

  • Hospital General Universitario de Alicante

    Alicante

    MARIA DE LA VEGA JOVANI CASANO

    Recruiting

  • Hospital Universitario Cruces

    Barakaldo

    ALEJANDRO FONOLLOSA CALDUCH

    Recruiting

  • Hospital Universitario de Gran Canaria Doctor Negrín

    Las Palmas de Gran Canaria

    FELIX M FRANCISCO HERNANDEZ

    Not yet recruiting

  • Complejo Asistencial Universitario de León

    León

    MIGUEL CORDERO COMA

    Not yet recruiting

  • Hospital Clínico San Carlos

    Madrid

    Luis Rodriguez Rodriguez

    Recruiting

  • Hospital Universitario 12 de Octubre

    Madrid

    ALFREDO JAVIER GARCIA GONZALEZ

    Not yet recruiting

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid

    ESTER CARREÑO SALAS

    Recruiting

  • Hospital Universitario Infanta Leonor

    Madrid

    LETICIA LOJO OLIVEIRA

    Recruiting

  • Hospital Universitario La Paz

    Madrid

    MARIA DIANA PEITEADO LOPEZ

    Recruiting

  • Hospital Universitario Infanta Sofía

    San Sebastián de los Reyes

    SANTIAGO MUÑOZ FERNANDEZ

    Not yet recruiting

  • Complejo Hospitalario Universitario de Canarias

    Santa Cruz de Tenerife

    MARIA BEATRIZ RODRIGUEZ LOZANO

    Not yet recruiting

  • Hospital Universitario Doctor Peset

    Valencia

    LUCIA MARTINEZ-COSTA PEREZ

    Recruiting

  • Instituto Universitario de Oftalmología Aplicada

    Valladolid

    LIDIA COCHO ARCHILES

    Not yet recruiting

Other trials in Spain

About this study

Official title: Efficacy, Safety and Cost-effectiveness of Methotrexate, Adalimumab, or Their Combination in Non-infectious Non-anterior Uveitis: a Randomized, Parallel 3 Arms, Active-controlled, Phase 3 Open Label With Blinded Outcome Assessment Study

Introduction: Non-infectious uveitis (NIUs) include a heterogeneous group of sight-threatening conditions. NIUs can be highly disabling and be associated with a profound impact in the quality-of-life (QoL) and wellbeing. Their correct management sometimes requires the use of immunosuppressive drugs (ISDs), which can be prescribed in monotherapy or in combination. Several observational studies have provided evidence that the use of ISDs in combination could be more effective than and as safe as their use in monotherapy. However, a direct comparison between these two treatment strategies has not been carried out yet.

Methods and analysis: The Combination THerapy with mEthotrexate and adalImumAb for uveitis (CoTHEIA) study is a phase III, multicenter, prospective, randomized, single-blinded with masked outcome assessment, parallel three arms with 1:1:1 allocation, active-controlled, superiority study design, comparing the efficacy, safety and cost-effectiveness of methotrexate (MTX), adalimumab (ADA), or their combination in non-infectious non-anterior uveitis. The duration of the treatment and follow-up will last up to 52 weeks. The complete and maintained resolution of the ocular inflammation will be assessed by masked evaluators (primary outcome). In addition to other secundray measures of efficacy (QoL, visual acuity, costs) and safety, we will identify subjects' subgroups with different treatment responses by developing prediction models based on machine learning techniques using genetic and proteomic biomarkers.

Conditions
Uveitis
Being tested
Methotrexate, Adalimumab, Adalimumab+Methotrexate
Medical subject headings
Uveitis

What participants receive

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

  • MethotrexateDrug

    Inicial dose 15mg/week increasing up to 25 mg/week

  • AdalimumabDrug

    At the Baselin visit adalimumab 80 mg subcutaneous loading dose followed a week later by 40 mg every-other-week starting at Week 1.

  • Adalimumab+MethotrexateDrug

    Adalimumab: at the Baseline visit 80 mg subcutaneous loading dose followed a week later by 40 mg every-other-week starting at Week 1.

    Methotrexate:Inicial dose 15mg/week increasing up to 25 mg/week

Study groups in NCT04798755
Study groupRoleWhat they receive
AdalimumabActive comparatorNot described
Receives: Drug: Adalimumab
MethotrexateActive comparatorNot described
Receives: Drug: Methotrexate
Adalimumab+MethotrexateExperimentalNot described
Receives: Drug: Adalimumab+Methotrexate

What is being measured

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

  1. Good Clinical Response

    Complete resolution of the ocular inflammatory signs, achieved within the first 16 weeks of the study, and maintained until week 52; no treatment failure due to safety or intolerability.

    Measured: 52 weeks

Secondary outcomes (10)

  1. Good Clinical Response

    Complete resolution of the ocular inflammatory signs, achieved within the first 16 weeks of the study, and maintained until week 52; no treatment failure due to safety or intolerability.

    Measured: week 16

  2. EuroQol-5D at each study visit

    We will use the EuroQol-5D (0-100, the higher the better quality of life) to compare the change in health-related quality of life between treatment strategies.

    Measured: Baseline, weeks 16 and 52.

  3. Visual Functioning Questionnaire-25 (VFQ-25)

    We will use the VFQ-25 (0-100, the higher the better quality of life) to compare the change in visual-related quality of life between treatment strategies

    Measured: Baseline, weeks 16 and 52.

  4. Hospital Anxiety and Depression Scale; HADS

    We will use the HADS (0-21 for either anxiety or depression, the higher the more severe anxiety/depression symptoms) to compare the change in anxiety and depression sympthoms between treatment strategies quality of life, anxiety and depression) between treatment strategies

    Measured: Baseline, weeks 16 and 52.

  5. Clinical components of the Good Clinical Response variable

    Presence of non active chorioretinal lesions; active retinal vascular inflammation; macular edema; ACC; vitreous haze; and loss of CVA secondary to inflammation

    Measured: Baseline, weeks 16 and 52.

  6. Time to inflammatory relapse.

    time from visit 16 weeks until end of the study, loss of follow-up or appearance of at least one ocular inflammatory manifestation, in those individuals achieving a Good Clinical Response.

    Measured: week 16.

  7. Best corrected visual acuity (BCVA)

    We will use the BCVA between treatment strategies

    Measured: Baseline, weeks 16 and 52.

  8. Anti-ADA antibodies (AAA).

    Presence of anti-ADA antibodies (AAA) in subjects receiving this study drug.

    Measured: Weeks 15, 27 and 51.

  9. Cost-efficacy

    Direct and indirect cost, and Incremental Cost Effectiveness Ratios

    Measured: Week 52.

  10. Safety: adverse events.

    Ocurrence of adverse events.

    Measured: Baseline, weeks 16 and 52.

Timeline

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

  1. First posted15 Mar 2021
  2. Study start12 Jan 2022
  3. Primary completion1 Oct 2024 (estimated)
  4. Study completion1 Oct 2025 (estimated)

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
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
192 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04798755
Sponsor's protocol ID
Co-THEIA
Acronym
Co-THEIA
Status last verified
Sep 2023
First submitted
9 Mar 2021
Last updated
21 Sep 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Data obtained through this study may be provided to qualified researchers with academic interest in uveitis. Data or samples shared will be coded, and donated to a Registered Biobank and made available under legal requirement. Approval of the request and execution of all applicable agreements are prerequisites to the sharing of data with the requesting party. Regarding dissemination, in order to communicate the clinical trial progress and findings to a broad group of stakeholders, we will elaborate a Dissemination plan which will include production of materials adapted to scientific meetings, scientific publications, patients, and other stakeholders. A summary of the final version of the study protocol will be made available through the Spanish Clinical Trial Registry (REEC) and Clinicaltrials.gov database. The promoter will be the only with access to the participant-level data, following the regulation on data protection.

Publications

  • Rivas AB, Lopez-Picado A, Calamia V, Carreno E, Cocho L, Cordero-Coma M, Fonollosa A, Francisco Hernandez FM, Garcia-Aparicio A, Garcia-Gonzalez J, Mondejar JJ, Lojo-Oliveira L, Martinez-Costa L, Munoz S, Peiteado D, Pinto JA, Rodriguez-Lozano B, Pato E, Diaz-Valle D, Molina E, Tebar LA, Rodriguez-Rodriguez L; CoTHEIA Study Group. Efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis: a protocol for a multicentre, randomised, parallel three arms, active-controlled, phase III open label with blinded outcome assessment study. BMJ Open. 2022 Mar 22;12(3):e051378. doi: 10.1136/bmjopen-2021-051378.

    PubMed 35318229

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Methotrexate, Adalimumab and Adalimumab+Methotrexate in people with Uveitis, run by Hospital San Carlos, Madrid at 14 sites in Spain.

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 25 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Spain. 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 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?

Results are not available in the source record.

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

Contact Luis Rodriguez Rodriguez (+0034-91330300 ext. 7560, lrrodriguez@salud.madrid.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Good Clinical Response (time frame: 52 weeks). 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 NCT04798755, 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 21 Sep 2023.

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