Clinical Trials Register

Summary
EudraCT Number:	2017-004700-22
Sponsor's Protocol Code Number:	1608185
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2018-01-17
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

2017-004700-22

A.3

Full title of the trial

Rotation or Change of Biotherapy After TNF blocker treatment failure for axial Spondyloarthritis: The ROC-SpA study

A.3.1

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

Rotation or Change of Biotherapy After TNF blocker treatment failure

A.4.1

Sponsor's protocol code number

1608185

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	CHU SAINT-Etienne
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	Ministère de la santé
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	CHU Saint-Etienne
B.5.2	Functional name of contact point	Project manager
B.5.3	Address:
B.5.3.1	Street Address	URCIP - Hôpital Nord - CHU Saint-Etienne
B.5.3.2	Town/ city	Saint-Etienne cedex 2
B.5.3.3	Post code	42055
B.5.3.4	Country	France
B.5.4	Telephone number	0477829458
B.5.5	Fax number	0477127820
B.5.6	E-mail	florence.rancon@chu-st-etienne.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	cosentyx
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Pharma
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
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	No
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.2.1.2	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.3.2	Product code	TNF Blocker
D.3.4	Pharmaceutical form
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INFLIXIMAB
D.3.9.1	CAS number	170277-31-3
D.3.9.2	Current sponsor code	infliximab
D.3.9.4	EV Substance Code	SUB02681MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ETANERCEPT
D.3.9.1	CAS number	185243-69-0
D.3.9.4	EV Substance Code	SUB01984MIG
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	50
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CERTOLIZUMAB PEGOL
D.3.9.1	CAS number	428863-50-7
D.3.9.4	EV Substance Code	SUB25423
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	400
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	GOLIMUMAB
D.3.9.1	CAS number	476181-74-5
D.3.9.4	EV Substance Code	SUB25638
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	50 to 100
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	No
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

axial Spondyloarthritis

E.1.1.1

Medical condition in easily understood language

Spondyloarthritis

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10071400
E.1.2	Term	Axial spondyloarthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Demonstrate that targeting IL-23/17 axis will provide a better clinical response at 24 weeks when compared to a second TNF blocker, after failure of a first TNF blocker in axSpA

E.2.2

Secondary objectives of the trial

1- Targeting IL-23/17 axis compared to a second TNF blocker will provide:
1.a- A better clinical response after failure of a first TNF blocker in axSpA at weeks 12 and 52.
1.b- A better maintenance of bDMARDs.
2- To compare tolerance of both strategies.
3- To compare the incremental cost-effectiveness ratio (ICER) of the IL23/17 strategy versus the 2nd TNF-blocker strategy.
4- To compare quality-adjusted life-year (QALY) between both strategies.
5- Investigating whether the pharmacokinetic parameters of TNF blockers (serum trough levels concentrations, specific antibody concentrations) measured at inclusion are predictive of a clinical response at W24.
6- Investigating whether the pharmacokinetic parameters of bDMARDs (serum trough levels concentrations, specific antibody concentrations) are associated with low disease activity.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Active axSPA with BASDAI>4 and ASDAS>3.5, who need change in TNF blocker treatment
• Aged over 18 years
• Inadequate response after at least 3 months to the 1st TNF blocker
• If non biologic DMARD treatment : stable dose for at least on month before inclusion
• If oral corticosteroids treatment : stable dose for at least on month before inclusion
• IfNSAIDs treatment : stable dose for at least on month before inclusion
• Ability to complete questionnaires
• Social security affiliation
• Informed written consent given

E.4

Principal exclusion criteria

• Any contra-indication to TNF blocker and/or secukinumab
• Inflammatory bowel diseases
• Existing pregnancy, lactation, or intended pregnancy within the next 15 months Active tuberculosis or other severe infections such as sepsis or opportunistic infections
• Active infections, including chronic or localised infections.
• Moderate to severe heart failure (NYHA classes III/IV)
• Impossibility to give informed consent
• Impossibility to be followed for 12 months

E.5 End points

E.5.1

Primary end point(s)

Proportion of axSpA patients with a clinical response ASAS40 at week 24.

The ASAS working group has proposed a measure that has been now used in several trials to measure the efficacy of new products on the symptoms of axSpA. The ASAS Response Criteria (ASAS 40) is defined as an improvement of at least 40% and absolute improvement of at least 10 units on a 0-100 mm scale in at least 3 of the following domains compared to values at inclusion:
• Patient global assessment measured on a VAS scale with extremes labelled “none” and “severe.”
• Pain assessment represented by the average of total and nocturnal pain scores, both measured on a VAS scale with extremes labelled “no pain” and “most severe pain.”
• Function represented by BASFI average of 10 questions regarding ability to perform specific tasks as measured by VAS with extremes labelled “easy” and “impossible.”
• Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI regarding morning stiffness as measured by VAS: one with extremes labelled “none” and “very severe”; the other marking duration of morning stiffness between “0” and “2 or more hours.”
Additionally, absence of deterioration (of at least 20% and absolute change of at least 10 units on a 0– 100 mm scale) in the remaining domain should be documented [29].

E.5.1.1

Timepoint(s) of evaluation of this end point

At week 24

E.5.2

Secondary end point(s)

1a/ Clinical response will also be assessed by the following criteria [22,30]:
- ASAS40 response rates at week 12 and 52;
- ASAS20 response rates at week 12, 24, and 52;
The ASAS20 response is based on the same principle with an improvement of at least 20%.
- Partial remission rates at week 12, 24, and 52;
Partial remission is defined by values lower than 20/100 in each 4 domains described above.
- ASDAS major improvement rates at week 12, 24, and 52;
ASDAS major improvement was defined by a variation of ASDAS-CRP≥2.

1b/ Maintenance rate of the bDMARDs will be compared in both strategies at week 12, 24, and 52.

2/ Tolerance of the treatment will be collected actively (specific questions on the different expected outcomes in the CRF) at each visit to the study with a focus on any kind of infection. Moreover, it will ask the patient to note on a booklet any side effects during the treatment to reduce the bias of memorisation.
3/ Medical direct and indirect costs will be compared in both strategies.
The incremental cost-effectiveness ratio (ICER) of the IL-23/17 strategy versus the 2nd TNF-blocker strategy is defined as follows :
Δ(CoûtIL23/17 – Coût2nd TNF) / Δ(Efficacité IL23/17 – Efficacité2nd TNF),
in which direct and indirect costs will be elicited from the payer (national health insurance) perspective, and effectiveness expressed in quality-adjusted life years (QALY) and derived from the EQ-5D-5L using French norms [31].

E.5.2.1

Timepoint(s) of evaluation of this end point

week 12, 24, and 52

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial 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:

250

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

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

300

F.4.2

For a multinational trial

F.4.2.1

In the EEA

300

F.4.2.2

In the whole clinical trial

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)

normal treatment of the condition

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

2018-02-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-02-19

P. End of Trial
P.	End of Trial Status	Ongoing

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