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Study to Evaluate the Efficacy and Safety of AMG 714 in Adult Patients With Type II Refractory Celiac Disease

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ClinicalTrials.gov Identifier: NCT02633020
Recruitment Status : Completed
First Posted : December 17, 2015
Results First Posted : December 27, 2019
Last Update Posted : December 27, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
Protocol CELIM-RCD-002 is designed to evaluate the efficacy and safety of AMG 714 for the treatment of adult patients with type II refractory celiac disease (RCD-II), an in-situ small bowel T-cell lymphoma.

Condition or disease Intervention/treatment Phase
Type II Refractory Celiac Disease (RCD-II) In-situ Small Bowel T-cell Lymphoma Biological: AMG 714 Biological: Placebo Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of AMG 714 in Adult Patients With Type II Refractory Celiac Disease, an In Situ Small Bowel T Cell Lymphoma
Actual Study Start Date : April 13, 2016
Actual Primary Completion Date : April 11, 2017
Actual Study Completion Date : May 2, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: AMG 714
Participants were administered 8 mg/kg AMG 714 via intravenous infusion on day 0, day 7 and every 2 weeks thereafter through week 10.
Biological: AMG 714
Administered via a 120-minute IV infusion for a total of 7 times over 10 weeks.

Placebo Comparator: Placebo
Participants were administered placebo via intravenous infusion on day 0, day 7 and every 2 weeks thereafter through week 10.
Biological: Placebo
Administered via a 120-minute IV infusion for a total of 7 times over 10 weeks.




Primary Outcome Measures :
  1. Percent Change From Baseline in the Percentage of Aberrant Intestinal Intraepithelial Lymphocytes With Respect to All Intraepithelial Lymphocytes [ Time Frame: Baseline and week 12 ]

    The primary endpoint in this study was the change form baseline in the percentage of aberrant intestinal intraepithelial lymphocytes (IELs) with respect to total IELs, as assessed by flow cytometry (Immunological Response 1).

    Intraepithelial lymphocytes (IELS) are white blood cells interspersed between epithelial cells of the small and large intestine where they function to preserve the integrity of the mucosal barrier by protecting the epithelium against pathogen or immune-induced pathology. In refractory coeliac disease type 2, aberrant intraepithelial lymphocytes make up 20% or more of total intraepithelial lymphocytes. Aberrant IELs were defined by flow cytometry as surface cluster of differentiation (CD)3-negative, intracellular CD3-positive IELs (sCD3-, icCD3+).



Secondary Outcome Measures :
  1. Percent Change From Baseline in the Percentage of Aberrant Intestinal Intraepithelial Lymphocytes With Respect to All Intestinal Epithelial Cells [ Time Frame: Baseline and week 12 ]
    Percent change from baseline in the percentage of aberrant intestinal IELs with respect to intestinal epithelial cells (Immunological Response 2) is a composite endpoint calculated by multiplying the percent of aberrant IEL versus total IELs (per flow cytometry) by the percent of total IEL versus intestinal epithelial cells as assessed by immunohistochemistry.

  2. Percent Change From Baseline in Villous Height to Crypt Depth (VH:CD) Ratio [ Time Frame: Baseline and week 12 ]

    Villi are the small fingerlike projections that line the small intestine and promote nutrient absorption and are often shortened in patients with celiac disease. Crypts are grooves between the villi that are often elongated in patients with celiac disease. A decreased VH:CD ratio indicates worsening disease and increases in the VH:CD ratio indicate an improvement in the histology of intestinal mucosa (Histological Response).

    Small bowel biopsies were performed at baseline and week 12; histological assessments were performed by a blinded central pathologist.


  3. Percentage of Participants With Improvement in Marsh Score at Week 12 [ Time Frame: Baseline and week 12 ]

    The Marsh classification system describes the stages of damage in the small intestine as seen under a microscope, with possible values of 0, 1, 2, 3a, 3b, or 3c. A score of 0 (best score) indicates that the intestinal lining is normal and celiac disease highly unlikely, a score of 3c (worst score) indicates increased intraepithelial lymphocytes, increased crypt hyperplasia and complete villi atrophy.

    Improvement is defined as a lower grade on the Marsh score scale compared to baseline.


  4. Percent Change From Baseline in Total Intraepithelial Lymphocyte Count at Week 12 [ Time Frame: Baseline and week 12 ]
    Small bowel biopsies were performed at baseline and week 12; histological assessments were performed by a blinded central pathologist. The total IEL count is the density of IELs vs intestinal epithelial cells measured by immunohistochemistry.

  5. Number of Weekly Bowel Movements at Baseline and Week 12 [ Time Frame: Baseline and week 12 ]
    Participants were asked to record every bowel movement during the study using an electronic diary. If no bowel movements were experienced by the participant on any given day, the participant was required to document this in the diary.

  6. Percentage of Participants With Diarrhea at Baseline and Week 12 [ Time Frame: Baseline and week 12 ]

    The Bristol Stool Form Scale (BSFS) is a pictorial aid to help participants identify the shape and consistency of their bowel movements. Participants were asked to complete this form daily using an electronic diary at the time of each bowel movement. The BSFS categorizes bowel movements into 7 types, from Type 1 (separate hard lumps, like nuts; hard to pass) to Type 7 (watery, no solid pieces, entirely liquid).

    Diarrhoea was defined at least one BSFS score >= 6 for the given week.


  7. Change From Baseline in Total Weekly Gastrointestinal Symptom Rating Scale (GSRS) Score at Week 12 [ Time Frame: Baseline and week 12 ]

    The GSRS is a 15-question 7-scale questionnaire used to assess 5 dimensions of gastrointestinal syndromes: diarrhea, indigestion, constipation, abdominal pain and reflux. Questions are scored between 1 (no discomfort at all) and 7 (very severe discomfort).

    The total GSRS score is calculated as the sum of the scores of all 15 questions, and ranges from 15 (no discomfort at all) to 105 (very severe discomfort in all 5 dimensions of gastrointestinal syndromes).


  8. Change From Baseline in Total Celiac Disease GSRS (CeD-GSRS) Score at Week 12 [ Time Frame: Baseline and week 12 ]

    The CeD-GSRS score is derived from a subset of 10 questions from the GSRS questionnaire (questions 1, 4-9, 11, 12 and 14), which are each assessed on a scale of 1 (no discomfort at all) to 7 (very severe discomfort).

    The total CeD-GSRS score ranges from 10 (no discomfort at all) to 70 (very severe discomfort in all celiac syndromes).




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of refractory celiac disease Type II (RCD-II)
  • Greater than 20% aberrant intraepithelial lymphocytes (IEL) as assessed by flow cytometry
  • On a gluten-free diet for at least 6 months
  • Avoid pregnancy

Exclusion Criteria:

  • Enteropathy-Associated T cell Lymphoma (EATL)
  • Infections
  • Immune suppression
  • Clinically significant co-morbidities

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02633020


Locations
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United States, California
Clinical Site
San Diego, California, United States
United States, New York
Clinical Site
New York, New York, United States
Finland
Clinical Site
Tampere, Finland
France
Clinical Site
Paris, France
Netherlands
Clinical Site
Amsterdam, Netherlands
Spain
Clinical Site
Madrid, Spain
Sponsors and Collaborators
Amgen
Investigators
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Study Director: Amgen, MD Amgen
  Study Documents (Full-Text)

Documents provided by Amgen:
Study Protocol  [PDF] July 11, 2016
Statistical Analysis Plan  [PDF] June 16, 2017

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02633020    
Other Study ID Numbers: CELIM-RCD-002
2015-004063-36 ( EudraCT Number )
First Posted: December 17, 2015    Key Record Dates
Results First Posted: December 27, 2019
Last Update Posted: December 27, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Publication in peer-reviewed journals

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, T-Cell
Celiac Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Metabolic Diseases