Clinical Trials Register

Summary
EudraCT Number:	2022-001316-26
Sponsor's Protocol Code Number:	APHP200007
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2022-06-02
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2022-001316-26

A.3

Full title of the trial

Multicenter, randomized, prospective trial comparing the Efficacy and Safety of Adalimumab to that of Tocilizumab in severe uveitis of Behçet’s disease
UVB Study

Etude multicentrique, randomisée, prospective comparant l'efficacité et la tolérance de I’Adalimumab et du Tocilizumab chez les sujets présentant une uvéite sévère dans un contexte de maladie de Behçet
Etude UVB

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

UVB: treatment of UVeitis in Behçet’s diseases with biologics

A.3.2

Name or abbreviated title of the trial where available

UVB

A.4.1

Sponsor's protocol code number

APHP200007

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Assistance Publique Hôpitaux de Paris / DRCI
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	French Ministry of health
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Assistance Publique Hôpitaux de Paris / DRCI
B.5.2	Functional name of contact point	Elodie SOLER
B.5.3	Address:
B.5.3.1	Street Address	Hôpital Saint-Louis, 1 avenue Claude Vellefaux
B.5.3.2	Town/ city	PARIS
B.5.3.3	Post code	75010
B.5.3.4	Country	France
B.5.6	E-mail	elodie.soler@aphp.fr

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Humira 40mg, solution injectable en stylo prérempli
D.2.1.1.2	Name of the Marketing Authorisation holder	AbbVie
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection in pre-filled pen
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Adalimumab
D.3.9.1	CAS number	331731-18-1
D.3.9.4	EV Substance Code	SUB20016
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	RoActemra 162 mg solution injectable en seringue préremplie
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tocilizumab
D.3.9.1	CAS number	375823-41-9
D.3.9.4	EV Substance Code	SUB20313
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	162
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

severe uveitis of Behçet’s disease

E.1.1.1

Medical condition in easily understood language

severe uveitis of Behçet’s disease

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10071139
E.1.2	Term	Behcet's uveitis
E.1.2	System Organ Class	100000004866

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the benefit of tocilizumab comparatively to that of adalimumab in sight-threatening Behçet’s disease uveitis at week 16.

Évaluer le bénéfice du tocilizumab par rapport à celui de l'adalimumab dans l'uvéite sévère de la maladie de Behçet à la semaine 16.

E.2.2

Secondary objectives of the trial

• To estimate and compare the change in best corrected visual acuity (BCVA)
• To evaluate and compare the safety of Adalimumab and tocilizumab
• To evaluate and compare the change in macular edema
• To evaluate and compare the change in other signs of ocular inflammation
• To evaluate and compare the effect on retinal vessel leakage
• To evaluate and compare the effect of Adalimumab and tocilizumab on steroid sparing
• To evaluate and compare the change in ocular inflammation in the anterior chamber
• To evaluate and compare the number and time to relapse of uveitis and the characteristics of uveitis at worsening.
• To evaluate and compare the time to treatment failure
• To estimate and compare the effect on extra ophthalmologic manifestations of BD.
• To estimate and compare the mean change in SF-36 quality of life and Behçet’s Disease Quality of Life Measure
• To estimate and compare the changes in BD Current Activity Form and Behcet’s Syndrome Activity Score

•Évaluer et comparer l'évolution de la BCVA
•Évaluer et comparer la sécurité de l'adalimumab et du tocilizumab
•Évaluer et comparer l'évolution de l'œdème maculaire
•Évaluer et comparer l'évolution d'autres signes d'inflammation oculaire
•Évaluer et comparer l'effet sur la fuite des vaisseaux rétiniens
•Évaluer et comparer l'effet de l'adalimumab et du tocilizumab sur l'épargne des stéroïdes
•Évaluer et comparer l'évolution de l'inflammation oculaire dans la chambre antérieure
•Évaluer et comparer le nb et le délai de rechute des uvéites et les caractéristiques des uvéites à l'aggravation.
•Évaluer et comparer le délai jusqu'à l'échec du traitement
•Évaluer et comparer l'effet sur les manifestations extra ophtalmologiques de la MB.
•Évaluer et comparer le chgt moyen de la qualité de vie du SF-36 et la mesure de la qualité de vie de la MB
•Évaluer et comparer les chgts dans le formulaire d'activité actuelle de la MB et le score d'activité du syndrome de Behcet

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age  18 at Inclusion
2. Provide written, informed consent prior to the performance of any study specific procedures
3. Diagnosis of Behçet’s disease according to the International Criteria for Behçet's Disease (ICBD) (see appendix 1) or history of aphtosis.
4. 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
5. Sight threatening uveitis defined according to the validated international definition as 2 lines of drop in visual acuity on a 10/10 scale, and/or retinal inflammation (macular oedema and/or retinal vasculitis).
6. 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
7. For female subjects of child-bearing potential, a negative pregnancy test (plasmatic or urinary)
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 and 5 months after stopping therapy for tocilizumab 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 :
 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).
9. A potential subject with a positive interferon-gamma release assay (IGRA) (e.g., QuantiFERON®-TB Gold or T-spot TB® Test) obtained within 6 months prior to inclusion is eligible if her/his chest X-ray does not show evidence suggestive of active TB disease and there are no clinical signs and symptoms of pulmonary and/or extra-pulmonary TB disease. 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. The treatment should be started at the latest at inclusion.
10. Affiliation to a social security system

E.4

Principal exclusion criteria

1. Infectious uveitis, masquerade syndromes, or uveitis due to causes other than BD uveitis
2. Active tuberculosis or history of untreated tuberculosis and/or severe infection
3. Positive HIV antibody and/or positive hepatitis B surface antigen and/or positive hepatitis C RNA, results obtained within 1 month prior to inclusion
4. 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.
5. History of severe allergic or anaphylactic reactions to monoclonal antibodies
6. History of multiple sclerosis and/or demyelinating disorder
7. Laboratory values assessed during Inclusion:
a. Neutrophil < 1.0  103/mm3
b. Platelet count < 80 103/mm3
c. ASAT or ALAT > 5 ULN
8. Treatment with anti-TNF and/or Tocilizumab therapy within 1 month prior to inclusion
9. if on azathioprine, mycophenolate mofetil, or methotrexate at the time of inclusion, these drugs must be withdrawn prior to receiving the tocilizumab or adalimumab dose on Day 0.
10. Stage III and IV New York Heart Association (NYHA) cardiac insufficiency
11. Severe renal (Glomerular filtration rates (GFR) <30ml/min) or liver insufficiency (prothrombin <50% without other causes)
12. Any live (attenuated) vaccine within 30 days prior to inclusion;

E.5 End points

E.5.1

Primary end point(s)

Efficacy will be defined by a complete remission of ocular involvement with prednisone lower or equal to 5 mg/day at week 16 after randomization.
Ocular involvement response to treatment will be evaluated according to the Standardization of Uveitis Nomenclature (SUN) Workgroup criteria.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 16

E.5.2

Secondary end point(s)

- Measures of corticosteroid sparing (e.g., percent meeting targets [lower than 0.1 mg/day/kg of prednisone], mean dose at week 16, and cumulative dose).
- Time to response onset,
- Measures of acute-phase reactants (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], at week 4, 8, 12, 16, 24, 36 and 48
- Rate and Time to occurrence of relapse or worsening while on study. (Relapse will be defined as the reappearance of clinical and/or paraclinical features of active disease or by the occurrence of new lesions or progression of preexisting lesions).
- Changes in Behcet’s Disease Current Activity Form and Behcet’s Syndrome Activity Score at week 8, 16 and 24
- Changes in other organs involved by BD at week 4, 8, 12, 16, 24, 36 and 48
- Changes in quality of life (QOL) (SF36v2 TM Health Survey) and Behcet’s Disease Quality of Life Measure at week 16 and 24
- Safety and tolerability of treatments in BD patients as assessed by frequency and severity of adverse clinical events at week 4, 8, 12, 16, 24, 36 and 48
- Changes in Tyndall, flare and Vitreous Haze at week 8, 16, 24, 36 and 48
- Changes in Best corrected visual acuity (ETDRS letters score) at week 8, 16, 24, 36 and 48
- Changes in central retinal thickness measured with Optical Coherence Tomography (OCT) at week 8, 16, 24, 36 and 48.
- Percentage of patients with central retinal thickness <300 microns at week 8, 16, 24, 36 and 48.
- Percentage of patients without retinal vessel leakage on retinal angiography at week 16, and at week 24, 36 and 48, in case of retinal vasculitis

E.5.2.1

Timepoint(s) of evaluation of this end point

Weeks 4, 8, 12, 16, 24, 36 and 48

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Expected normal treatment of that condition

Traitement habituel pour cette pathologie

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-09-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-09-12

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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