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Crohn's DiseasePhase 3ADACALNCT01562951

Assessment of Mucosal Activity to Improve the Prognosis of Patients With Crohn's Disease Treated With Immunosuppressants

A Phase 3 study testing ADALIMUMAB in people with Crohn's Disease and Mucosal Inflammation, run by Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa at 30 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study will test that individualized treatment in patients with Crohn's Disease in remission or mild clinical activity under immunosuppressants may improve prognosis, rather than just treating flares. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Crohn's Disease, Mucosal Inflammation
What is being tested?
ADALIMUMAB
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
15 participants
Where
30 sitesin 3 countries
Study dates
Oct 2012to Mar 2014
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 9Show fewer
  • CDAI score ≤ 220.
  • Calprotectin > or = 250µg/g and/or hsCRP > or = 5mg/L.
  • Significant lesions seen during colonoscopy, as defined by CDEIS.

Who cannot join

  • 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
Show all 31Show fewer
  • 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:
  • Live vaccines.
  • 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.
  • Oral corticosteroids (eg., Prednisone, budesonide) should be discontinued for 3 months before study inclusion.
  • Antibiotics for CD. Only antibiotics used to treat a concurrent infection are allowed.
  • 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
  • Monoclonal antibodies or anti-TNF drugs.
  • 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:
  • Aspartate transaminase (AST) or alanine transaminase (ALT) > 2 x the upper limit of the reference range;
  • Total bilirubin ≥ 3 mg/dL (51 μmol/L);
  • 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

Trial locations and contacts

30 sites in 3 countries.

30 sites in 3 countries

France12 sites

  • CHU Amiens - Hospital Nord

    Amiens, Amiens, 80054

  • CHU Tours - Hospital Trousseau

    Chambray, Tours, 76031

  • Hospital Beaujon

    Clichy, Clichy, 92110

  • CHRU Lille - Hospital Claude Huriez

    Lille, Lille, 59037

  • CHU Lyon Sud

    Lyon, Lyon, 69495

  • CHU Nantes

    Nantes, Nantes, 44093

  • Hospital Saint Louis

    Paris, Paris, 75010

  • CHU Bordeaux - Hospital Haut-Leveque

    Pessac, Bordeaux, 33604

  • CHRU Reims - Hospital Robert Debre

    Reims, Reims, 51092

  • CHU Rouen - Hospital Charles Nicolle

    Rouen, Rouen, 76031

  • CH Saint Etienne - Hospital Nord

    Saint-Etienne, Saint Etienne, 42270

  • CHU Nancy - Hospital de Brabois Adultes

    Vandœuvre-lès-Nancy, Nancy, 54500

Other trials in France

Spain12 sites

  • Hospital Germans Trias i Pujol

    Badalona, Barcelona

  • Hospital Santa Creu i Sant Pau

    Barcelona, Barcelona, 08025

  • Hospital Universitario Reina Sofia

    Córdoba, Andalusia, 14004

  • Hospital Doctor Negrin

    Las Palmas de Gran Canarias, Canary Islands, 35010

  • Hospital Universitario La Princesa

    Madrid, Madrid, 28005

  • Hospital Gregorio Marañón

    Madrid, Madrid, 28007

  • Hospital Ramón y Cajal

    Madrid, Madrid, 28034

  • Hospital de Manises

    Manises, Valencia, 46940

  • Complejo Hospitalario Santiago de Compostela

    Santiago de Compostela, A coruña

  • Hospital Virgen del Rocío

    Seville, Sevilla, 41013

  • Hospital Clínico de Valencia

    Valencia, Valencia, 46010

  • Hospital Lozano Blesa

    Zaragoza, Zaragoza

Other trials in Spain

Belgium6 sites

  • Imeldaziekenhuis Bonheiden

    Bonheiden, Bonheiden, 2820

  • Hospital Erasme Bruxelles

    Brussels, Brussels Capital, 1070

  • Hospital Saint Luc Bruxelles

    Brussels, Brussels Capital, 1200

  • Hospital University Gent

    Ghent, Gent, 9000

  • Centre Hospitalier Universitaire de Liege

    Liège, Liege, 4000

  • Heiling Hartzieknhuis Roeselare

    Roeselare, Roeselare, 8800

Other trials in Belgium

About this study

Official title: 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

This study will test that individualized treatment in patients with Crohn's Disease in remission or mild clinical activity under immunosuppressants may improve prognosis, rather than just treating flares.

Read the detailed description

Patients will be prescreened for inclusion criteria one week before the start of screening at Visit 0 (Prescreening Visit). Patients must be on stable doses of azathioprine/mercaptopurine. Patients will be given a diary to record their CD symptoms for the seven days prior to Visit 1. At Visit 1 (Screening Visit 1), patients will have their CDAI score assessed based upon their diary information. Patients with CDAI ≤ 220 will then have both calprotectin and hsCRP testing done. Patients with calprotectin > or = 250µg/g and/or hsCRP > or = 5mg/L will be notified and told to schedule Visit 2 within three weeks. At Visit 2 (Screening Visit 2), patients will undergo a colonoscopy. A Crohn's Disease Endoscopic Index of Severity (CDEIS) will be used to determine the endoscopic activity. Patients with significant endoscopic lesions will be notified and asked to enroll in the study.

Patients will be randomized into the study at Visit 3 (Randomization Visit, same day of Visit 2 in results available). Due to the cost and invasiveness of the colonoscopy, the Screening Visit 2 colonoscopy will serve as the baseline for the study, should the patient be enrolled. Drug will also be dispensed at this visit. Eligible patients will be randomized in a 1:1 ratio to receive either adalimumab or placebo during the treatment period, along with continuing their current immunosuppressive maintenance treatment at a stable dose. Treatment in both arms will be induction at 160/80mg and maintenance on 40 mg every other week.

Patients will return for follow up visits every 12 weeks until the final follow-up visit at 48 weeks (Visit 7), where another colonoscopy will be performed. Patients who terminate early from the study for any reason will be asked to return for a follow-up visit, where Visit 7 procedures will be performed.

Before week 48, if a patient has an increase of more than 50% in either calprotectin and/or hsCRP over baseline and above the thresholds at any regular visit, a follow-up visit will be performed two weeks later. If the 50% increase is still observed another colonoscopy will be performed, within two weeks of the follow-up visit. If patients still have significant endoscopic lesions, study product will be intensified to 40 mg weekly. This will include patients on placebo in order to preserve the double-blind aspect of the study.

Being tested
ADALIMUMAB, Placebo
Keywords
Crohn's disease, mucosal inflammation, lesions
Medical subject headings
Crohn Disease, Mucositis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ADALIMUMABDrug

    Also called HUMIRA

    Adalimumab at 160/80 mg and maintained on 40 mg eow until next colonoscopy performed at week 48. If before week 48, an increase of more than 50% is observed in calprotectin and/or hsCRP from baseline, over two consecutive follow up visits 2 weeks apart, the colonoscopy will be performed earlier. If patients have still significant endoscopic lesions, adalimumab or adalimumab placebo will be intensified to 40 mg weekly.

  • PlaceboDrug

    PLACEBO at 160/80 mg and maintained on 40 mg eow until next colonoscopy performed at week 48. If before week 48, an increase of more than 50% is observed in calprotectin and/or hsCRP from baseline, over two consecutive follow up visits 2 weeks apart, the colonoscopy will be performed earlier. If patients have still significant endoscopic lesions, adalimumab or adalimumab placebo will be intensified to 40 mg weekly

Study groups in NCT01562951
Study groupRoleWhat they receive
PLACEBOPlacebo comparatorTreatment with placebo
Receives: Drug: Placebo
ADALIMUMABActive comparatorTreatment with Adalimumab
Receives: Drug: ADALIMUMAB

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    The therapeutic failure is defined as any of following cases:

    1. CDAI > 220 with at least 70-point increase from baseline over two consecutive visits 12 weeks apart or CDAI > 300 at any time point during the study;
    2. need of any change in therapy for CD except the ones planned per protocol in each group of the study;
    3. need of surgery related to CD or of stricture endoscopic dilatation.

    Measured: Every 12 weeks up to Week 48

Secondary outcomes (17)

  1. The rate of therapeutic failure (see the definition of primary endpoint) up to week 24

    Measured: up to week 24

  2. Change in CDEIS from baseline to week 48

    CDEIS = Crohn's Disease Endoscopic Index of Severity.

    Measured: up to week 48

  3. The rate of mucosal healing (CDEIS=0) at week 48

    CDEIS = Crohn's Disease Endoscopic Index of Severity

    Measured: at week 48

  4. The rate of CDEIS remission (CDEIS<=3) at week 48

    CDEIS = Crohn's Disease Endoscopic Index of Severity

    Measured: at week 48

  5. The rate of CDEIS response, which is defined as a decrease of at least 4 points in CDEIS from baseline to week 48

    CDEIS = Crohn's Disease Endoscopic Index of Severity

    Measured: from baseline up to week 48

  6. Change in CDAI from baseline to week 12, 24, 36 and 48

    CDAI = Crohn's Disease Activity Index.

    Measured: from baseline to week 12, 24, 36 and 48

  7. Change in the global score based on IBDQ from baseline to week 12, 24, 36, and 48.

    IBDQ = Inflammatory Bowel Disease Questionnaire.

    Measured: from baseline to week 12, 24, 36, and 48.

  8. Area Under the Curve (AUC) over 48 weeks for CDAI

    Measured: 48 weeks

  9. The number of surgical interventions related to CD up to 24 and 48 weeks

    Measured: up to 24 and 48 weeks

  10. The rate of hospital admissions related to the disease, to the treatment side effects or other causes up to weeks 24 or 48

    Measured: up to weeks 24 or 48

  11. The rate of serious AEs between the two strategies up to 24 and 48 weeks

    Measured: up to 24 and 48 weeks

  12. The rate of serious AEs requiring the cessation of the ongoing treatment between the two strategies up to 24 and 48 weeks.

    Measured: up to 24 and 48 weeks

  13. The accuracy of calprotectin/hsCRP to predict therapeutic failure 12 weeks in advance

    Measured: 12 weeks

  14. The correlation between calprotectin, hsCRP and CDAI at any time points during the study.

    Pearson Product-Moment Correlation will be used to evaluate correlations between calprotectin, hsCRP and CDAI at all scheduled visits.

    Measured: 48 weeks

  15. The correlation between calprotectin/hsCRP and CDEIS or mucosal healing at Baseline and Week 48.

    Pearson Product-Moment Correlation will also be used to evaluate between calprotectin (and hsCRP) and CDEIS at Baseline and Week 48.

    Measured: at Baseline and Week 48.

  16. Change in the scores based on WPAI from baseline to week 12, 24, 36 and 48

    WPAI = Work Productivity and Activity Impairment Questionnaire

    Measured: from baseline to week 12, 24, 36 and 48

  17. The change in calprotectin and hsCRP from baseline to week 12, 24, 36, and 48

    Measured: from baseline to week 12, 24, 36, and 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Mar 2012 (estimated)
  2. Study startOct 2012
  3. Primary completionMar 2014
  4. Study completionMar 2014

Why it stopped: Not enough patient population according to selection criteria to complete the study

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01562951
Sponsor's protocol ID
A12-771
Acronym
ADACAL
Status last verified
May 2016
First submitted
13 Mar 2012
Last updated
4 May 2016
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ADALIMUMAB in people with Crohn's Disease and Mucosal Inflammation, run by Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa at 30 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in France, Spain, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Not enough patient population according to selection criteria to complete the study). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The primary efficacy endpoint is the rate of therapeutic failure up to week 48 (time frame: Every 12 weeks up to Week 48). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01562951.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2016.

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