Type II Refractory Celiac Disease (RCD-II)Phase 2NCT02633020
Study to Evaluate the Efficacy and Safety of AMG 714 in Adult Patients With Type II Refractory Celiac Disease
A Phase 2 study testing AMG 714 in people with Type II Refractory Celiac Disease (RCD-II) and In-situ Small Bowel T-cell Lymphoma, run by Amgen at 6 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type II Refractory Celiac Disease (RCD-II), In-situ Small Bowel T-cell Lymphoma
- What is being tested?
- AMG 714
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 6 sitesin 5 countries
- Study dates
- 13 Apr 2016to 2 May 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Enteropathy-Associated T cell Lymphoma (EATL)
- Infections
- Immune suppression
- Clinically significant co-morbidities
Trial locations and contacts
6 sites in 5 countries.
6 sites in 5 countries
United States2 sites
Clinical Site
New York, New York
Clinical Site
San Diego, California
About this study
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
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.
- Being tested
- AMG 714, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 714Biological
Administered via a 120-minute IV infusion for a total of 7 times over 10 weeks.
PlaceboBiological
Administered via a 120-minute IV infusion for a total of 7 times over 10 weeks.
| Study group | Role | What they receive |
|---|---|---|
| AMG 714 | Experimental | Participants were administered 8 mg/kg AMG 714 via intravenous infusion on day 0, day 7 and every 2 weeks thereafter through week 10. Receives: Biological: AMG 714 |
| Placebo | Placebo comparator | Participants were administered placebo via intravenous infusion on day 0, day 7 and every 2 weeks thereafter through week 10. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in the Percentage of Aberrant Intestinal Intraepithelial Lymphocytes With Respect to All Intraepithelial Lymphocytes
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+).
Measured: Baseline and week 12
Secondary outcomes (8)
Percent Change From Baseline in the Percentage of Aberrant Intestinal Intraepithelial Lymphocytes With Respect to All Intestinal Epithelial Cells
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.
Measured: Baseline and week 12
Percent Change From Baseline in Villous Height to Crypt Depth (VH:CD) Ratio
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.
Measured: Baseline and week 12
Percentage of Participants With Improvement in Marsh Score at 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.
Measured: Baseline and week 12
Percent Change From Baseline in Total Intraepithelial Lymphocyte Count at 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.
Measured: Baseline and week 12
Number of Weekly Bowel Movements at 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.
Measured: Baseline and week 12
Percentage of Participants With Diarrhea at 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.
Measured: Baseline and week 12
Change From Baseline in Total Weekly Gastrointestinal Symptom Rating Scale (GSRS) Score at 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).
Measured: Baseline and week 12
Change From Baseline in Total Celiac Disease GSRS (CeD-GSRS) Score at 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).
Measured: Baseline and week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2015 (estimated)
- Study start13 Apr 2016
- Primary completion11 Apr 2017
- Study completion2 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type II Refractory Celiac Disease (RCD-II)Studies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Amgen, MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02633020
- Sponsor's protocol ID
- CELIM-RCD-002
- Other IDs
- 2015-004063-36, 2015
- Status last verified
- Nov 2019
- First submitted
- 28 Nov 2015
- Last updated
- 27 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Publication in peer-reviewed journals
- Expanded access
- Available
Publications
Cellier C, Bouma G, van Gils T, Khater S, Malamut G, Crespo L, Collin P, Green PHR, Crowe SE, Tsuji W, Butz E, Cerf-Bensussan N, Macintyre E, Parnes JR, Leon F, Hermine O, Mulder CJ; RCD-II Study Group Investigators. Safety and efficacy of AMG 714 in patients with type 2 refractory coeliac disease: a phase 2a, randomised, double-blind, placebo-controlled, parallel-group study. Lancet Gastroenterol Hepatol. 2019 Dec;4(12):960-970. doi: 10.1016/S2468-1253(19)30265-1. Epub 2019 Sep 4.
PubMed 31494097
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02633020
- Acronym / sponsor ID
- CELIM-RCD-002
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 13 Apr 2016 (actual)
- Primary completion
- 11 Apr 2017 (actual)
- Study completion
- 2 May 2017 (actual)
- First posted
- 17 Dec 2015 (estimated)
- Results
- Posted 27 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AMG 714 | Experimental | Biological: AMG 714Participants were administered 8 mg/kg AMG 714 via intravenous infusion on day 0, day 7 and every 2 weeks thereafter through week 10. |
| Placebo | Placebo comparator | Biological: PlaceboParticipants were administered placebo via intravenous infusion on day 0, day 7 and every 2 weeks thereafter through week 10. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- Enteropathy-Associated T cell Lymphoma (EATL)
- Infections
- Immune suppression
- Clinically significant co-morbidities
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMG 714Administered via a 120-minute IV infusion for a total of 7 times over 10 weeks. | Biological | AMG 714 |
| PlaceboAdministered via a 120-minute IV infusion for a total of 7 times over 10 weeks. | Biological | Placebo |
Primary outcome
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+).
8 secondary outcomes
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 Villous Height to Crypt Depth (VH:CD) Ratio
Time frame: Baseline and week 12
Percentage of Participants With Improvement in Marsh Score at Week 12
Time frame: Baseline and week 12
Percent Change From Baseline in Total Intraepithelial Lymphocyte Count at Week 12
Time frame: Baseline and week 12
Number of Weekly Bowel Movements at Baseline and Week 12
Time frame: Baseline and week 12
Percentage of Participants With Diarrhea at Baseline and Week 12
Time frame: Baseline and week 12
Change From Baseline in Total Weekly Gastrointestinal Symptom Rating Scale (GSRS) Score at Week 12
Time frame: Baseline and week 12
Change From Baseline in Total Celiac Disease GSRS (CeD-GSRS) Score at Week 12
Time frame: Baseline and week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31494097Cellier C, Bouma G, van Gils T, Khater S, Malamut G, Crespo L, Collin P, Green PHR, Crowe SE, Tsuji W, Butz E, Cerf-Bensussan N, Macintyre E, Parnes JR, Leon F, Hermine O, Mulder CJ; RCD-II Study Group Investigators. Safety and efficacy of AMG 714 in patients with type 2 refractory coeliac disease: a phase 2a, randomised, double-blind, placebo-controlled, parallel-group study. Lancet Gastroenterol Hepatol. 2019 Dec;4(12):960-970. doi: 10.1016/S2468-1253(19)30265-1. Epub 2019 Sep 4.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Publication in peer-reviewed journals
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amgen, MD study director
Amgen
6 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AMG 714 in people with Type II Refractory Celiac Disease (RCD-II) and In-situ Small Bowel T-cell Lymphoma, run by Amgen at 6 sites in 5 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 4 inclusion and 4 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: finished, as of the sponsor's last update on 27 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Finland, France, Netherlands, Spain. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percent Change From Baseline in the Percentage of Aberrant Intestinal Intraepithelial Lymphocytes With Respect to All Intraepithelial Lymphocytes (time frame: Baseline and week 12). 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 NCT02633020, which also lists 1 linked publication.
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 27 Dec 2019; AzTrials last refreshed its copy on 7 Nov 2026.