Clinical Trials Register

Summary
EudraCT Number:	2011-003966-34
Sponsor's Protocol Code Number:	A12-771
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-10-11
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2011-003966-34

A.3

Full title of the trial

The ADACAL Study: cAlprotectin and hsCRP as markers of a new Diagnostic-therapeutic strAtegy that assesses muCosal Activity to individuaLize treatment and improve the prognosis of patients with Crohn’s disease treated with immunosuppressants

A.3.1

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

Biomarkers in diagnosis & treatment of patients with Crohn’s disease treated with immunosuppressants

A.4.1

Sponsor's protocol code number

A12-771

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	Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU)
B.1.3.4	Country	Spain
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	Abbott Laboratories
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Grupo Español Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU)
B.5.2	Functional name of contact point	President GETECCU
B.5.3	Address:
B.5.3.1	Street Address	Gran Vía nº 81 - 5º Dpto. 10
B.5.3.2	Town/ city	Bilbao
B.5.3.3	Post code	48011
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34944278855
B.5.5	Fax number	+34944278808
B.5.6	E-mail	fgomollon@gmail.com

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
D.2.1.1.2	Name of the Marketing Authorisation holder	Abbott Laboratories Ltd
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	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	range
D.3.10.3	Concentration number	40 to 160
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection in pre-filled syringe
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Crohn's disease (CD) is an inflammatory disease of the intestines that primarily causes abdominal pain, diarrhea, vomiting, or weight loss.

E.1.1.1

Medical condition in easily understood language

Crohn’s disease is an inflammatory disease of the digestive tract.

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the effect of individualized treatment according to a new calprotectin/ high-sensitivity C-reactive protein (hsCRP)-based diagnostic-therapeutic strategy on the mid-term outcome in Crohn’s Disease (CD) patients.

E.2.2

Secondary objectives of the trial

- To assess the effect of an individualized treatment according to a new calprotectin and hsCRP based diagnostic-therapeutic strategy on mucosal healing, quality of life, work productivity, number of hospital admissions, and surgical interventions.
- To determine the value of calprotectin and hsCRP in predicting therapeutic failure, and mucosal healing.
- To correlate hsCRP with calprotectin.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Age 18-75 years old.
• Patients with CD diagnosis confirmed by colonoscopy.
• Patients with inflammatory CD of terminal ileal, colonic or ileocolonic location.
• Maintenance treatment with at least 2 mg/kg/day for azathioprine/ 1 mg/kg/day for mercaptopurine or the highest dosage tolerated in patients who could not tolerate this dosage, at least 6 months.
• Willingness to sign informed consent.
• If female of childbearing age, be post-menopausal, surgically sterile, or willing to use a reliable form of birth control for the duration of the study (such as physical barrier [patient and partner], contraceptive pill or patch, spermicide and barrier, or intrauterine device) and for at least five months after the last adalimumab treatment.
• Able to comply with the requirements of the study.
• CDAI score ≤ 220.
• Calprotectin ≥ 250µg/g and/or hsCRP ≥ 5mg/L.
• Significant lesions seen during colonoscopy, as defined by CDEIS.

E.4

Principal exclusion criteria

• Patients with an ostomy, or ileoanal pouch (subject with previous ileo-rectal anastomosis are not excluded), draining fistula, abscess.
• Patients who had intestinal resection within one year.
• Symptomatic stricture either diagnosed by colonoscopy or clinically suspected and confirmed by imaging techniques.
• Prior treatment with any anti-tumor necrosis factor (TNF) drug.
• Patients receiving rectal treatment 1 month before inclusion.
• Signs of active infection.
• Previous history of active untreated or inadequately treated tuberculosis (TB) or latent TB. Patients should be screened for latent TB as per local guidelines or clinical practice in the country of study conduct. Patients with latent TB should be treated with standard antimycobacterial therapy (for at least 4 weeks) before initiating biologic therapy and have a negative CRX for active TB at screening.
• Subjects with a poorly controlled medical condition such as: uncontrolled diabetes with documented history of recurrent infections, unstable ischemic heart disease, moderate to severe congestive heart failure (New York Heart Association [NYHA] class III or IV), recent cerebrovascular accident, or any other condition which, in the opinion of the Investigator or the sponsor, would put the subject at risk by participation in the protocol.
• Signs of colon cancer or dysplasia.
• Signs of severe or unstable renal, hepatic, gastrointestinal, cardiovascular, respiratory, neurological, psychiatric, or hematological disease.
• Signs of cancer in the past five years, except for localized and treated basal cell skin cancer or cervical cancer.
• Patients who are pregnant or nursing.
• Concomitant treatment with:
o Live vaccines.
o 5-ASA compounds:
 Rectal 5-ASA should be discontinued at least 4 weeks before study inclusion.
 Oral 5-ASA must be at a stable dose for at least 4 weeks before study inclusion. If oral 5-ASA has recently been discontinued, 4 weeks should pass before study inclusion.
o Oral corticosteroids (eg., Prednisone, budesonide) should be discontinued for 3 months before study inclusion.
o Antibiotics for CD. Only antibiotics used to treat a concurrent infection are allowed.
o Immunomodulators:
Patients receiving therapy with azathioprine/mercaptopurine must have been on a stable dose for at least 12 weeks before inclusion and must continue with the same dose during the study.
 No treatment with other known immunomodulators (eg., methotrexate, 6-thioguanine [6-TG], cyclosporine, tacrolimus, sirolimus, ustekinumab, pentoxifylline, or mycophenolate mofetil) or experimental drugs (eg., factor colony stimulating granulocyte macrophage [GM-CSF]) within 6 months.
o Monoclonal antibodies or anti-TNF drugs.
o Aspirin or Non-steroidal anti-inflammatory drugs (NSAIDs). Treatment with aspirin and/or NSAIDS should not occur for more than 15 consecutive days before collecting of the stool sample for Calprotectin and performing the colonoscopy.
• Screening laboratory and other analyses show any of the following abnormal results:
o Aspartate transaminase (AST) or alanine transaminase (ALT) > 2 x the upper limit of the reference range;
o Total bilirubin ≥ 3 mg/dL (51 μmol/L);
o Serum creatinine > 1.6 mg/dL (144 μmol/L).
• History of any drug or alcohol abuse in the past 2 years.
• Receipt of other study product within 3 months of inclusion in this study.
• Patients employed by the sponsor or in any relationship of dependence with the sponsor and/or investigator.
• Staff at the study center.
• Hypersensitivity to the active substance or to any of the excipients

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the rate of therapeutic failure up to week 48.

E.5.1.1

Timepoint(s) of evaluation of this end point

Data will be evaluated in combination after last patient last visit.

E.5.2

Secondary end point(s)

• The rate of therapeutic failure up to week 24.
• Change in CDEIS from baseline to week 48.
• The rate of mucosal healing (CDEIS=0) at week 48.
• The rate of CDEIS remission (CDEIS<=3) at week 48.
• The rate of CDEIS response, which is defined as a decrease of at least 4 points in CDEIS from baseline to week 48.
• Change in CDAI from baseline to week 12, 24, 36 and 48.
• Change in the global score based on IBDQ from baseline to week 12, 24, 36, and 48.
• Change in the scores based on WPAI from baseline to week 12, 24, 36 and 48.
• Area Under the Curve (AUC) over 48 weeks for CDAI.
• The number of surgical interventions related to CD up to 24 and 48 weeks.
• The rate of hospital admissions related to the disease, to the treatment side effects or other causes up to weeks 24 or 48.
• Calprotectin levels based on PhiCal tests;
• hsCRP levels

E.5.2.1

Timepoint(s) of evaluation of this end point

Data will be evaluated in combination after last patient last visit.

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

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)

Yes

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

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)

E.8.2.2

Placebo

Yes

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

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

End of trial is last patient last visit.

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:

180

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

180

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

Yes

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.4.2

For a multinational trial

F.4.2.1

In the EEA

180

F.4.2.2

In the whole clinical trial

180

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 standard of care will resume after the end of trial.

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

2011-11-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-12-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-02-12

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials