Clinical trial NCT01291810: Clinical Efficacy of TNFa Kinoid in Crohn's Disease Patients
Official title: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Clinical Efficacy, Safety and Immunogenicity of Neovacs' TNFα-Kinoid in Adult Subjects With Crohn's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Crohn's Disease
Lead sponsor: Neovacs
Sponsor class: INDUSTRY
First posted: 2011-02-08
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The safety and immunogenicity of the TNFα-Kinoid (TNF-K) have been evaluated in a phase I-II clinical study conducted in subjects with Crohn's Disease (CD). Preliminary results of clinical efficacy are promising.

The principal aim of the present study is to confirm the clinical efficacy of the TNF-K in subjects with moderate to severe CD. Subjects with secondary resistance or intolerance to anti-TNFα monoclonal antibodies will be enrolled in this trial. In addition, the immune responses and the safety elicited by TNF-K will also be evaluated.


Eligibility criteria: Inclusion Criteria:

1. Male or female aged 18 to 65 years, inclusive.
2. Have had a diagnosis of Crohn's disease for at least 6 months.
3. Moderate to severe active Crohn's disease defined as a Crohn's Disease Activity Index (CDAI) score ≥ 220 and ≤ 450, and presence of colonic mucosal ulcerations in at least 2 segments, or ulcerations on ≥ 10% of the mucosal surface if only one segment is involved.
4. Have developed secondary resistance to anti-TNFα therapy.

Exclusion Criteria:

1. Primary non-response to a previously received treatment directed against TNFα Or Intolerance related to the primary pharmacological effect of anti-TNFα such as for instance, but not limited to, severe or opportunistic infections and demyelinating or autoimmune diseases.
2. History of severe systemic bacterial, fungal, viral, or parasitic infections within the 3 months prior to screening; or the occurrence of any acute infection within 2 weeks of the first administration of study drug.
3. Treatment with immunosuppressive or immunomodulatory drugs

Primary outcomes:
measure: Clinical remission, defined as a CDAI score ≤ 150 points at week 8.
timeFrame: Week 8
Secondary outcomes:
measure: Clinical responses, defined as a decrease of at least 70 points (CDAI-70) and at least 100 points (CDAI-100) in the CDAI score at week 8 vs baseline
timeFrame: week 8
measure: Endoscopic response, defined as a reduction of at least 50% in the Crohn's Disease Endoscopic Index of Severity (CDEIS) score or in the Simple Endoscopic Score for Crohn's Disease (SES-CD) at week 12 vs baseline
timeFrame: week 12
measure: Biological response as defined by a decrease or normalization of calprotectin levels in stools
timeFrame: Week 12
measure: Safety assessments will be conducted throughout the study and will include physical examinations, vital signs, 12-lead electrocardiograms (ECGs), clinical laboratory evaluations, and the recording of adverse events (AEs).
timeFrame: Week 28
measure: Immunogenicity: o Anti-TNFα antibodies by Enzyme-Linked Immunosorbent Assay (ELISA) o Anti-TNFα neutralizing antibody activity o Anti-KLH antibodies by ELISA
timeFrame: week 12
Other outcomes:
Locations:
city: Bonheiden
country: Belgium
facility: Imelda Clinic
city: Brussels
country: Belgium
facility: Cliniques Universitaires St Luc
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Katholiek Unversiteit van Leuven
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital St. Georgi
city: Sofia
country: Bulgaria
facility: Alexandrovska University Hospital
city: Sofia
country: Bulgaria
facility: Medical Institute- Ministry of Interior Clinic of Gastroenterology
city: Sofia
country: Bulgaria
facility: MMA Clinic of Gastroenterology
city: Sofia
country: Bulgaria
facility: UMHAT "St. Ivan Rilsky"
city: Sofia
country: Bulgaria
facility: UMHAT Queen Yoanna - ISUL
city: Varna
country: Bulgaria
facility: Clinic of Gastroenterology/ University Hospital Varna
city: Rijeka
country: Croatia
facility: Clinical Hospital Centre Rijeka
city: Zadar
country: Croatia
facility: General Hospital Zadar
city: Zagreb
country: Croatia
facility: Clinical Hospital Centre Zagreb,
city: Zagreb
country: Croatia
facility: University Hospital Dubrava
city: Hradec Králové
country: Czech Republic
facility: Faculty Hospital in Hradec Králové
city: Olomouc
country: Czech Republic
facility: Faculty Hospital Olomouc
city: Prague
country: Czech Republic
facility: IBD Clinical and Research Centre
city: Amiens
country: France
facility: CHU Hôpital Nord
city: Bordeaux
country: France
facility: Hôpital Haut-Lévêque
city: Caen
country: France
facility: CHU Caen
city: Caen
country: France
facility: CHU Côte de Nacre
city: Clichy
country: France
facility: Hopital Beaujon (APHP)
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital de Bicêtre
city: Lille
country: France
facility: Hôpital A Huriez CHRU Lille
city: Nancy
country: France
facility: CHU Nancy Hôpital Brabois
city: Nice
country: France
facility: CHU de Nice Hôpital de l'Archet
city: Paris
country: France
facility: Hôpital St Louis
city: Rouen
country: France
facility: CHU Rouen
city: Toulouse
country: France
facility: CHU Rangueil
city: Berlin
country: Germany
facility: Charité Campus Virchow-Klinikum
city: Berlin
country: Germany
facility: Gastroenterologische Spezialpraxis
city: Berlin
country: Germany
facility: Klinik mit Schwerpunkt Gastroenterologie, Campus Charité Mitte
city: Braunschweig
country: Germany
facility: Klinikum Braunschweig
city: Essen
country: Germany
facility: Klinik für Allg. Innere Medizin, Gastroenterologie und Diabetologie, Kliniken-Essen-Mitte/Evang. Huyssenstiftung
city: Halle
country: Germany
facility: Universitätsklinik und Poliklinik für Innere Medizin I
city: Hamburg
country: Germany
facility: Asklepios Westklinikum Hamburg
city: Hamburg
country: Germany
facility: Hamburgisches Forschungsinstitut für CED
city: Hamburg
country: Germany
facility: I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Herne
country: Germany
facility: Gastroenterologische Gemeinschaftspraxis im Ärztehaus am Ev. Krankenhaus Herne
city: Jena
country: Germany
facility: Klinik für Innere Medizin II Abteilung Gastroenterologie, Hepatologie, Infektiologie
city: Kiel
country: Germany
facility: Klinik für Innere Medizin I
city: Köln
country: Germany
facility: Abteilung Innere Medizin Evangelisches Krankenhaus Kalk gGmbH
city: Leipzig
country: Germany
facility: Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten
city: Mainz
country: Germany
facility: I. Med. Klinik und Poliklinik
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Budapest
country: Hungary
facility: Fővárosi Önkormányzat Péterfy Sándor utcai Kórháza
city: Budapest
country: Hungary
facility: Semmelweis Egyetem ÁOK
city: Debrecen
country: Hungary
facility: DE OEC
city: Amsterdam
country: Netherlands
facility: Academic Medical Center (AMC)
city: Amsterdam
country: Netherlands
facility: Free University Medical Centre in Amsterdam (VUMC)
city: Bucharest
country: Romania
facility: Colentina Clinical Hospital
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute
city: Bucharest
country: Romania
facility: Mediclass Sananova SRL
city: Timisoara
country: Romania
facility: Dr. Citu Outpatient Clinic
city: Timisoara
country: Romania
facility: Polyclinic Private Practice Algomed SRL
Study officials:
References: