Treatment FOr Corticosteroid Dependent UveitiS

Non Infectious Uveitis Clinical Trial

— FOCUS  

Official title:

Randomized Controlled Multicenter Study Comparing Efficacy and Safety of Adalimumab to That of Mycophenolate Mofetil in Steroid Dependent Non-infectious Uveitis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06258915
• Other study ID #: APHP211032
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: March 1, 2024
• Est. completion date: November 1, 2027

Study information

• Verified date: January 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Bahram BODAGHI, Pr
• Phone: +33142163728
• Email: bahram.bodaghi[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

FOCUS is the first prospective randomized study comparing standard of care (mycophenolate mofetil) to adalimumab in recently active non infectious uveitis (NIU) with steroid dependency. There is no firm evidence or randomized trials that compared classical immunosuppressive compounds to biological agents; or identified the best treatment in this condition. The burden of NIU has been reduced with the use of immunosuppressive agents and biologics, raising the question of which of these compounds should be preferentially used in recently active NIU with steroid dependency.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: November 1, 2027
• Est. primary completion date: June 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

1. Provide written, informed consent prior to the performance of any study-specific procedures

2. =18 years of age

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 posterior, or pan- uveitis confirmed by documented medical history

4. Recent activity of Non Infectious Uveitis 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:

• Active chorioretinal or retinal vascular lesion
• Presence of macular edema by optical coherence.
• = 2+ anterior chamber cells (Standardization of Uveitis Nomenclature [SUN] criteria)
• = 2+ vitreous haze (National Eye Institute [NEI]/SUN criteria)

5. Chest X-ray (postero-anterior and lateral) or CT-scanner results within 12 weeks prior to inclusion with no evidence of active Tuberculosis, active infection, or malignancy

6. A potential subject with a positive interferon-gamma release assay (IGRA) (e.g.,

QuantiFERON®-TB Gold or T-spot TB® Test) at inclusion is eligible if:

1. Her/his chest X-ray does not show evidence suggestive of active tuberculosis disease

2. And there are no clinical signs and symptoms of pulmonary and/or extra-pulmonary tuberculosis disease.

3. And these subjects with a latent tuberculosis infection who have not already received a prophylactic tuberculosis treatment must agree in advance to complete such a treatment course.

7. For female subjects of child-bearing potential: a negative pregnancy test at inclusion

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 Mycophenolate mofetil (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 Clinical Trial Falicitation Group (CTFG) recommendations). Such methods include:

For Female subjects :

1. combined (estrogen and progestogen containing) hormonal contraception associated

with inhibition of ovulation 1:

• oral
• intravaginal
• transdermal

2. progestogen-only hormonal contraception associated with inhibition of ovulation:

• oral
• injectable
• implantable

3. intrauterine device (IUD)

4. intrauterine hormone-releasing system (IUS)

5. bilateral tubal occlusion

6. vasectomised partner

7. 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 :

1. use of condoms

2. vasectomy (with documentation of azoospermia)

3. sexual abstinence

9. Affiliated to a social security system

Exclusion Criteria:

1. Infectious uveitis, masquerade syndromes (idiopathic uveitis is permitted)

2. Isolated anterior uveitis

3. Monocular patient

4. Active tuberculosis

5. Positive HIV serology or Hepatitis C Virus (HCV) Hepatitis B Virus (HBV) Ag test

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. History of severe allergic or anaphylactic reactions to monoclonal antibodies, mycophenolate mofetil, rifampicin, isoniazid or fluorescein

8. Infection requiring treatment with intravenous antibiotics within 3 weeks prior to inclusion

9. History of multiple sclerosis and/or demyelinating disorder

10. Laboratory values assessed during inclusion:

• Hemoglobin < 8g/dL
• Whole Blood Count (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. 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. Stage III and IV New York Heart Association (NYHA) cardiac insufficiency

13. Pregnancy or breastfeeding

14. Under legal protection

15. Participation in another interventional study involving human participants or in the exclusion period

Related Conditions & MeSH terms

• Non Infectious Uveitis
• Uveitis

Intervention

Drug:
• Adalimumab
Adalimumab (80mg at day 0, then 40mg/14 days from W1 to W35 subcutaneously)
• Mycophenolate Mofetil
2 g/day orally for 36 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment failure rate	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; Score from 20/10 (best vision) to 20/2400 (worst vision).; 2- step increase in anterior chamber cell grade and/or in vitreous haze relative to baseline. Anterior chamber cells scored from 0 (None) to 4+ (intense: fibrin or plastic aquerous) and Vitreous haze Scored from 0 (<1 cell in field) to +4 (>100 cells in field); absence of steroid discontinuation between week 13 and week 19 (as per protocol); or any additional immunosuppressive drug or injectable steroids	At week 36
Secondary	Time to treatment failure		Up to week 55
Secondary	Best corrected visual acuity	Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).	At week 4
Secondary	Best corrected visual acuity	Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).	At week 8
Secondary	Best corrected visual acuity	Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).	At week 12
Secondary	Best corrected visual acuity	Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).	At week 16
Secondary	Best corrected visual acuity	Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).	At week 20
Secondary	Best corrected visual acuity	Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).	At week 24
Secondary	Best corrected visual acuity	Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).	At week 30
Secondary	Best corrected visual acuity	Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).	At week 36
Secondary	Best corrected visual acuity	Snellen score in each eye. Score from 20/10 (best vision) to 20/2400 (worst vision).	At week 55
Secondary	Anterior chamber cell grade in each eye	Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).	At week 4
Secondary	Anterior chamber cell grade in each eye	Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).	At week 8
Secondary	Anterior chamber cell grade in each eye	Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).	At week 12
Secondary	Anterior chamber cell grade in each eye	Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).	At week 16
Secondary	Anterior chamber cell grade in each eye	Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).	At week 20
Secondary	Anterior chamber cell grade in each eye	Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).	At week 24
Secondary	Anterior chamber cell grade in each eye	Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).	At week 30
Secondary	Anterior chamber cell grade in each eye	Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).	At week 36
Secondary	Anterior chamber cell grade in each eye	Score from 0 (None) to 4+ (intense: fibrin or plastic aqueous).	At week 55
Secondary	Vitreous haze grade in each eye.	Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)	At week 4
Secondary	Vitreous haze grade in each eye.	Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)	At week 8
Secondary	Vitreous haze grade in each eye.	Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)	At week 12
Secondary	Vitreous haze grade in each eye.	Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)	At week 16
Secondary	Vitreous haze grade in each eye.	Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)	At week 20
Secondary	Vitreous haze grade in each eye.	Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)	At week 24
Secondary	Vitreous haze grade in each eye.	Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)	At week 30
Secondary	Vitreous haze grade in each eye.	Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)	At week 36
Secondary	Vitreous haze grade in each eye.	Nussenblatt score, Score from 0 (<1 cell in field) to +4 (>100 cells in field)	At week 55
Secondary	Central retinal thickness in each eye from baseline		At week 4
Secondary	Central retinal thickness in each eye from baseline		At week 8
Secondary	Central retinal thickness in each eye from baseline		At week 12
Secondary	Central retinal thickness in each eye from baseline		At week 16
Secondary	Central retinal thickness in each eye from baseline		At week 20
Secondary	Central retinal thickness in each eye from baseline		At week 24
Secondary	Central retinal thickness in each eye from baseline		At week 30
Secondary	Central retinal thickness in each eye from baseline		At week 36
Secondary	Central retinal thickness in each eye from baseline		At week 55
Secondary	Proportion of patients with central macular thickness< 300 microns		At week 4
Secondary	Proportion of patients with central macular thickness< 300 microns		At week 8
Secondary	Proportion of patients with central macular thickness< 300 microns		At week 12
Secondary	Proportion of patients with central macular thickness< 300 microns		At week 16
Secondary	Proportion of patients with central macular thickness< 300 microns		At week 20
Secondary	Proportion of patients with central macular thickness< 300 microns		At week 24
Secondary	Proportion of patients with central macular thickness< 300 microns		At week 30
Secondary	Proportion of patients with central macular thickness< 300 microns		At week 36
Secondary	Proportion of patients with central macular thickness< 300 microns		At week 55
Secondary	Time to optical coherence tomographic (OCT) evidence of macular edema in at least one eye		Up to week 55
Secondary	National Eye Institute Visual Functioning Questionaire-25 (VFQ-25) composite score	Note after responses converted: 100=Best, 0=Worst possible score	At week 12
Secondary	National Eye Institute Visual Functioning Questionaire-25 (VFQ-25) composite score	Note after responses converted: 100=Best, 0=Worst possible score	At week 24
Secondary	National Eye Institute Visual Functioning Questionaire-25 (VFQ-25) composite score	Note after responses converted: 100=Best, 0=Worst possible score	At week 36
Secondary	Measures of corticosteroid sparing	Percent meeting targets [<0.1 mg/kg/day prednisone], mean change, mean dose at week 55, and cumulative dose	Up to week 55
Secondary	Cumulative incidence of relapse		Up to week 55
Secondary	Number of relapses		Up to week 55
Secondary	Number of clinical manifestations of underlying disease	Depending on the underlying disease	Up to week 55
Secondary	Frequency and severity of adverse events		Up to week 55
Secondary	Treatment discontinuation		Up to week 55