“Randomized controlled multicenter study comparing efficacy and safety of adalimumab to that of mycophenolate mofetil in steroid dependent non-infectious uveitis” - FOCUS

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Eye Diseases [C11]

Trial duration

1 Jul 2024 → ongoing

Decision date (initial)

2023-10-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Direction Générale de l’Offre des Soins du Ministère de la santé et de la prévention

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The objective is to compare the efficacy of adalimumab (80mg at day 0, then 40mg/14 days from W1 to W35 subcutaneously) with that of standard of care (mycophenolate mofetil [2g/day orally] for 36 weeks) in recently active non-infectious intermediate, posterior uveitis, and pan-uveitis with steroid dependency.

Secondary objectives 9

1. Comparing adalimumab (80mg at day 0, then 40mg/14 days from W1 to W35 subcutaneously) to standard of care (mycophenolate mofetil [(2g/day orally)] for 36 weeks): -To evaluate the cumulative incidence of treatment failure up to W55 after inclusion
2. - To evaluate the change in best corrected visual acuity (BCVA, Snellen) from baseline to week W55 ;
3. - To evaluate the change in ocular inflammation in the anterior chamber and vitreous from baseline to week W55;
4. - To evaluate the change in other signs including vessel leakage, from baseline to week W36;
5. - To evaluate the presence of macular edema from baseline to week W55;
6. - To evaluate the quality of life related to uveitis, from inclusion to W55;
7. - To evaluate steroid sparing effect from baseline to W55;
8. - To evaluate the number and time to relapse of uveitis; and the characteristics of uveitis at worsening from baseline to W55;
9. - To evaluate the safety of adalimumab and mycophenolate mofetil (up to W55)

Conditions and MedDRA coding

recently active non-infectious intermediate, posterior, and pan-uveitis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. The eligibility criteria will be checked at the screening visit (which takes place four weeks maximum prior to inclusion visit) and at the inclusion/randomization visit. Adult patients meeting the following criteria may be included in the study: 1. Provide written, informed consent prior to the performance of any study specific procedures
2. 2. ≥18 years of age
3. 3. 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 intermediate, posterior, or pan- uveitis confirmed by documented medical history
4. 4. Recent activity of NIU as defined by the presence of at least 1 of the following parameters in either eye within the 3 months prior to inclusion visit despite >7mg/day of oral prednisone: a) Active chorioretinal or retinal vascular lesion b) Presence of macular edema by optical coherence. c) ≥ 2+ anterior chamber cells (Standardization of Uveitis Nomenclature [SUN] criteria) d) ≥ 2+ vitreous haze (National Eye Institute [NEI]/SUN criteria)
5. 5. Chest X-ray or CT-scanner results within 12 weeks prior to inclusion with no evidence of active Tuberculosis, active infection, or malignancy
6. 6. A potential subject with a positive interferon-gamma release assay (IGRA) (e.g., QuantiFERON®-TB Gold or T-spot TB® Test) obtained within 12 weeks prior to inclusion is eligible if: a. Her/his chest X-ray does not show evidence suggestive of active TB disease b. And there are no clinical signs and symptoms of pulmonary and/or extra-pulmonary TB disease. c. And these subjects with a latent TB infection who have not already received a prophylactic TB treatment must agree in advance to complete such a treatment course.
7. 7. For female subjects of child-bearing potential: a negative pregnancy test at inclusion
8. 8. 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 months and 5 months after stopping therapy for MMF and adalimumab, respectively, unless sterility is confirmed. The simultaneous use of two complementary methods of contraception is preferable. 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: For Female subjects : a. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation 1: ▪ oral ▪ intravaginal ▪ transdermal b. progestogen-only hormonal contraception associated with inhibition of ovulation: ▪ oral ▪ injectable ▪ implantable c. intrauterine device (IUD) d. intrauterine hormone-releasing system (IUS) e. bilateral tubal occlusion f. vasectomised partner g. 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). For male subjects : a. use of condoms b. vasectomy (with documentation of azoospermia) c. sexual abstinence
9. 9. Affiliated to a social security system

Exclusion criteria 15

1. Subjects will not be included in the study if they meet any of the following criteria: 1. Infectious uveitis, masquerade syndromes (idiopathic uveitis is permitted)
2. 2. Isolated anterior uveitis
3. 3. Monophtalmic patient
4. 4. Active tuberculosis
5. 5. Positive HIV serology or HCV HBs Ag test
6. 6. History of malignancy within 5 years prior to Inclusion other than carcinoma in situ of the cervix, non-metastatic squamous or basal cell carcinoma of the skin.
7. 7. History of severe allergic or anaphylactic reactions to monoclonal antibodies, mycophenolate mofetil, rifampicin, isoniazid or fluorescein
8. 8. Infection requiring treatment with intravenous antibiotics within 3 weeks prior to inclusion
9. 9. History of multiple sclerosis and/or demyelinating disorder
10. 10. Laboratory values assessed during inclusion: • Hemoglobin < 8g/dL • WBC < 2.0 x 103/mm3 • Platelet count < 80 x 103/mm3 • Glomerular filtration rates (GFR) <30ml/min. • Transaminases > 3 times upper normal value
11. 11. Use of the following systemic treatments during the specified periods: • Treatment with any systemic alkylating agents within 12 months prior to inclusion (e.g., cyclophosphamide, chlorambucil) • Any live (attenuated) vaccine within 4 weeks prior to inclusion.
12. 12. Stage III and IV New York Heart Association (NYHA) cardiac insufficiency
13. 13. Pregnancy or breastfeeding
14. 14. Under legal protection
15. 15. Participation in another interventional study involving human participants or in the exclusion period at the end of a previous study involving human participants, if applicable

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint is the treatment failure rate at 36 weeks. Treatment failure is defined by any of the following in at least one eye: new active, inflammatory chorioretinal or retinal vascular lesions; worsening of best corrected visual acuity (BCVA) by>3 lines; 2-step increase in anterior chamber cell grade and/or in vitreous haze relative to baseline ; absence of steroid discontinuation between week 13 and week 19 or any additional immunosuppressive drug or injectable steroids

Secondary endpoints 12

1. Time to treatment failure up to W55
2. Snellen BCVA in each eye, at W4, W8, W12, W16, W20, W24, W30, W36 and W55
3. Anterior chamber cell grade in each at W4, W8, W12, W16, W20, W24, W30, W36 and W55
4. Vitreous haze grade (SUN criteria) in each eye at W4, W8, W12, W16, W20, W24, W30, W36 and W55
5. Central retinal thickness in each eye from baseline at W4, W8, W12, W16, W20, W24, W30, W36 and W55
6. Proportion of patients with central macular thickness< 300 microns at W4, W8, W12, W16, W20, W24, W30, W36 and W55
7. Time to optical coherence tomographic (OCT) evidence of macular edema in at least one eye, up to W55
8. NEI Visual Functioning Questionaire-25 (VFQ-25) composite score, at W12, W24, and W36
9. Measures of corticosteroid sparing (e.g., percent meeting targets [<0.1 mg/kg/day prednisone], mean change, mean dose at week 55, and cumulative dose)
10. Cumulative incidence of relapse and number of relapses up to W55
11. Safety and tolerability of treatments as assessed by the frequency and severity of adverse events and treatment discontinuation from baseline to Week 55
12. - Percentage of patients without chorioretinal or vascular lesions on retinal angiography, up to w36

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr David SAADOUN

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Breno MELO

Locations

1 EU/EEA country · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications