A Phase 2a/b Study of the Efficacy and Safety of Subcutaneous Amlitelimab in Adults With Nonresponsive Celiac Disease
- Conditions
- Coeliac DiseaseCeliac Disease
- Interventions
- Registration Number
- NCT06557772
- Lead Sponsor
- Sanofi
- Brief Summary
This is a Phase 2a/b, randomized, double-blind, placebo-controlled, parallel-group, 6-arm study to evaluate the efficacy and safety of amlitelimab in adult participants with non-responsive celiac disease (NRCD) who are on a gluten free diet (GFD) with and without simulated inadvertent gluten exposure (SIGE).
The primary purpose of this study is to demonstrate the efficacy of subcutaneous (SC) amlitelimab in male and female participants (aged 18 to 75 years, inclusive) with NRCD. The study will assess the effect of amlitelimab when compared to placebo on gluten induced changes in the intestinal mucosa as measured by the villous height to crypt depth (Vh:Cd) ratio. The effect of amlitelimab on participant-reported celiac signs and symptoms along with the safety, tolerability, and pharmacokinetics of amlitelimab will also be studied.
Study details include:
The study duration will be up to 48 weeks (including a 16-week safety follow-up period) with 10 visits for participants who opt not to enter the optional long-term extension.
The study duration will be up to 172 weeks (including an 8-week safety follow-up period) with 22 visits for participants who enter the optional long-term extension.
The double-blind placebo-controlled treatment duration will be up to 28 weeks.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 204
- Participants must be 18 to 75 years of age inclusive, at the time of signing the informed consent.
- Participants with physician-diagnosed celiac disease with documented history of biopsy-proven celiac disease confirmed by medical records or physician statement.
- Participants who have self-reported attempt to maintain a GFD (and confirmed via questionnaire) for at least 12 consecutive months and must be willing to maintain their current diet for the duration of study participation.
- Participants have an adequate comprehension of a GFD as assessed by the Investigator.
- Participants willing to undergo all assessments in the protocol, including 2 esophagogastroduodenoscopies with duodenal biopsies.
- Participants who completed CDSD with ≥ 75% compliance from screening until randomization.
- During screening, participants must have at least one gastrointestinal symptom (i.e., diarrhea, abdominal pain, bloating, or nausea) of moderate or greater severity, as measured by the CDSD Gastrointestinal Domain, on at least 3 days out of any consecutive 7-day period considered by the investigator to be related to gluten exposure (i.e., due to celiac disease). The symptom can vary, but severity must be moderate or greater on three or more days. Participants must meet symptom criteria to undergo baseline esophagogastroduodenoscopy (EGD).
Participants are excluded from the study if any of the following criteria apply:
- A diagnosis of any severe complication of celiac disease, such as refractory celiac disease type 1 (RCD I) requiring immune suppressive medication, or type 2 (RCD II), enteropathy associated T-cell lymphoma (EATL), ulcerative jejunitis, or recent (within 12 months of screening) GI perforation.
- Presence of other active inflammatory GI disorders, including but not limited to the following: inflammatory bowel disease, eosinophilic esophagitis, diverticulitis, helicobacter infection, gastroenteritis or colitis, and microscopic colitis (requiring treatment) in the 6 months before screening. A history of treated erosive esophagitis is not an exclusion. Abnormalities found during baseline EGD or biopsy that are consistent with an inflammatory GI disorder other than celiac disease are exclusionary.
- Presence of other systemic autoimmune diseases including scleroderma, psoriatic or rheumatoid arthritis, and lupus. Participants with thyroid disease that has been well-controlled for at least 6 months, prior to screening, and participants with well-controlled type 1 diabetes (glycosylated hemoglobin < 9 % and no hospitalization or emergency room visit in the last 12 months for hyperglycemia or hypoglycemia) can be included per investigator judgement.
- Known or suspected severe enteric infection (viral, bacterial, or parasitic) within 6 months before screening. Severe enteric infection is defined as requiring a visit to the emergency room, hospitalization, or treatment with antibiotics or anti-infectives due to infection. Non-enteric viral infections, either resolved or well-controlled are not exclusionary.
- Any active or chronic infection including helminthic infection requiring systemic treatment within 4 weeks prior to screening (1 week in the event of superficial skin infections).
- Known history of or suspected significant current immunosuppression or hyposplenism, including history of invasive opportunistic or invasive helminthic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration.
- Any malignancies or history of malignancies prior to enrollment (except for non-melanoma skin cancer that has been excised and completely cured for more than 5 years prior to enrollment).
- History of solid organ or stem cell transplant.
- Ongoing use, or use in the 3 months before screening, of medications known to cause villus abnormalities (eg, mycophenolate mofetil, azathioprine, methotrexate, olmesartan (other angiotensin receptor blockers are allowed), CTLA4 inhibitors, and PD-1/PD-L1 inhibitors).
- Ongoing chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) of more than 2 doses per week, except acetylsalicylic acid/aspirin ≤100 mg daily for prophylactic use.
- Any ongoing treatment with systemic immunosuppressants, systemic corticosteroids, or use of oral budesonide in the 12 weeks before screening.
- Ongoing use of over-the-counter digestive enzymes or supplements, other than lactase, including those for gluten digestion and oral pharmaceutical probiotic supplements. Probiotics in foods (e.g., yogurt) are permitted.
- Concurrent participation in any other clinical study, including non-interventional studies.
- Prior administration of investigational agents to treat celiac disease within 5 half-lives of any agent, or one year from any tolerogenic agent.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Amlitelimab dose 1 + Gluten-free product (GFP) Gluten-free product (GFP) Amlitelimab SC as per protocol + GFP Amlitelimab dose 2 + GFP Amlitelimab Amlitelimab SC as per protocol + GFP Amlitelimab dose 2 + GFP Gluten-free product (GFP) Amlitelimab SC as per protocol + GFP Amlitelimab dose 3 + GFP Gluten-free product (GFP) Amlitelimab SC as per protocol + GFP Placebo + GFP Gluten-free product (GFP) Placebo SC as per protocol + GFP Placebo + SIGE Placebo Placebo SC as per protocol + SIGE Placebo + SIGE SIGE Placebo SC as per protocol + SIGE Amlitelimab dose 1 + SIGE SIGE Amlitelimab SC as per protocol + SIGE Placebo + GFP Placebo Placebo SC as per protocol + GFP Amlitelimab dose 1 + Gluten-free product (GFP) Amlitelimab Amlitelimab SC as per protocol + GFP Amlitelimab dose 3 + GFP Amlitelimab Amlitelimab SC as per protocol + GFP Amlitelimab dose 1 + SIGE Amlitelimab Amlitelimab SC as per protocol + SIGE
- Primary Outcome Measures
Name Time Method Change in Villus Height to Crypt Depth Ratio (Vh:Cd) from baseline to Week 28 Baseline to Week 28 Change in Vh:Cd ratio.
- Secondary Outcome Measures
Name Time Method Change in Celiac Disease Symptom Diary (CDSD) Gastrointestinal (GI) symptom severity score Baseline to Week 28 The CDSD is a patient report outcome instrument that assesses common celiac symptoms (abdominal pain, bloating, tiredness, nausea, and diarrhea). GI symptom severity score ranges from 0-20 with higher score indicating more severe disease.
Percentage of participants who experienced treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) and adverse events of special interest (AESI) during the placebo-controlled treatment period and the long-term extension Baseline to Week 168 Percentage of participants with potentially clinically significant abnormalities (PCSA) for vital signs and clinical laboratory assessments during the placebo-controlled treatment period and the long-term extension Baseline to Week 168 Percentage of participants discontinued from study treatment due to TEAEs during the placebo-controlled treatment period and the long-term extension Baseline to Week 168 Serum amlitelimab concentrations measured at prespecified timepoints Baseline to Week 168 Incidence of antidrug antibodies (ADAs) of amlitelimab Baseline to Week 168
Trial Locations
- Locations (101)
Investigational Site Number : 0320012
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 7920003
🇹🇷Gaziantep, Turkey
FOMAT Medical Research - inSite Digestive Health Care - Arcadia- Site Number : 8400052
🇺🇸Arcadia, California, United States
Ventura County Gastroenterology Medical Group- Site Number : 8400010
🇺🇸Camarillo, California, United States
Om Research LLC- Site Number : 8400001
🇺🇸Lancaster, California, United States
United Gastroenterologists - Los Alamitos- Site Number : 8400014
🇺🇸Los Alamitos, California, United States
Advanced Research Institute - Denver- Site Number : 8400048
🇺🇸Denver, Colorado, United States
Wellness Clinical Research - Miami Lakes- Site Number : 8400040
🇺🇸Miami Lakes, Florida, United States
Center for Digestive Health- Site Number : 8400013
🇺🇸Orlando, Florida, United States
GCP Clinical Research- Site Number : 8400007
🇺🇸Tampa, Florida, United States
Treasure Valley Medical Research- Site Number : 8400006
🇺🇸Boise, Idaho, United States
Hutchinson Clinic- Site Number : 8400020
🇺🇸Hutchinson, Kansas, United States
Boston Specialists- Site Number : 8400051
🇺🇸Boston, Massachusetts, United States
Berkshire Medical Center, Inc.- Site Number : 8400017
🇺🇸Pittsfield, Massachusetts, United States
Gastroenterology Associates of Western Michigan - Wyoming- Site Number : 8400004
🇺🇸Wyoming, Michigan, United States
Mayo Clinic Hospital Rochester- Site Number : 8400049
🇺🇸Rochester, Minnesota, United States
Advanced Research Institute- Site Number : 8400036
🇺🇸Reno, Nevada, United States
Sanmora Bespoke Clinical Research Solutions- Site Number : 8400015
🇺🇸East Orange, New Jersey, United States
M3 Wake Research- Site Number : 8400008
🇺🇸Raleigh, North Carolina, United States
Velocity Clinical Research - Providence- Site Number : 8400002
🇺🇸East Greenwich, Rhode Island, United States
ClinSearch - Chattanooga - Shallowford Road- Site Number : 8400012
🇺🇸Chattanooga, Tennessee, United States
Quality Medical Research- Site Number : 8400018
🇺🇸Nashville, Tennessee, United States
MedCare Pharma- Site Number : 8400016
🇺🇸Houston, Texas, United States
LinQ Research, LLC- Site Number : 8400028
🇺🇸Pearland, Texas, United States
DM Clinical Research - Tomball- Site Number : 8400042
🇺🇸Tomball, Texas, United States
Advanced Research Institute - Odgen- Site Number : 8400044
🇺🇸Ogden, Utah, United States
Velocity Clinical Research - Salt Lake City- Site Number : 8400023
🇺🇸West Jordan, Utah, United States
Clinical Research Partners - Richmond - Forest Avenue- Site Number : 8400011
🇺🇸Richmond, Virginia, United States
Investigational Site Number : 0320010
🇦🇷Quilmes, Buenos Aires, Argentina
Investigational Site Number : 0320008
🇦🇷San Isidro, Buenos Aires, Argentina
Investigational Site Number : 0320005
🇦🇷Rosario, Santa Fe, Argentina
Investigational Site Number : 0320002
🇦🇷San Miguel de Tucumán, Tucumán, Argentina
Investigational Site Number : 0320007
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 0320001
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 0320009
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 0320003
🇦🇷Córdoba, Argentina
Investigational Site Number : 0360002
🇦🇺Sydney, New South Wales, Australia
Investigational Site Number : 0360001
🇦🇺Mackay, Queensland, Australia
Investigational Site Number : 0360005
🇦🇺Melbourne, Victoria, Australia
Investigational Site Number : 0560002
🇧🇪Brussels, Belgium
Investigational Site Number : 0560001
🇧🇪Leuven, Belgium
Centro de Pesquisas da Clínica IBIS- Site Number : 0760006
🇧🇷Salvador, Bahia, Brazil
Chronos Pesquisa Clínica- Site Number : 0760002
🇧🇷Brasília, Distrito Federal, Brazil
Hospital São Lucas da PUCRS - Porto Alegre - Avenida Ipiranga- Site Number : 0760001
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Praxis Pesquisa Medica- Site Number : 0760008
🇧🇷Santo Andre, São Paulo, Brazil
Investigational Site Number : 1240001
🇨🇦Vancouver, British Columbia, Canada
Investigational Site Number : 1240002
🇨🇦Victoria, British Columbia, Canada
Investigational Site Number : 1520006
🇨🇱Concepción, Biobío, Chile
Investigational Site Number : 1520005
🇨🇱Talcahuano, Biobío, Chile
Investigational Site Number : 1520007
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1520004
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1520001
🇨🇱Santiago, Chile
Investigational Site Number : 2030002
🇨🇿Brno, Czechia
Investigational Site Number : 2030006
🇨🇿Havířov, Czechia
Investigational Site Number : 2030005
🇨🇿Klatovy, Czechia
Investigational Site Number : 2030001
🇨🇿Prague, Czechia
Investigational Site Number : 2030003
🇨🇿Prague, Czechia
Investigational Site Number : 2460002
🇫🇮Helsinki, Finland
Investigational Site Number : 2460003
🇫🇮Tampere, Finland
Investigational Site Number : 2460001
🇫🇮Turku, Finland
Investigational Site Number : 2500002
🇫🇷Nice, France
Investigational Site Number : 2500001
🇫🇷Paris, France
Investigational Site Number : 2760004
🇩🇪Berlin, Germany
Investigational Site Number : 2760001
🇩🇪Halle, Germany
Investigational Site Number : 2760002
🇩🇪Mainz, Germany
Investigational Site Number : 3000001
🇬🇷Athens, Greece
Investigational Site Number : 3000002
🇬🇷Athens, Greece
Investigational Site Number : 3760002
🇮🇱Afula, Israel
Investigational Site Number : 3760006
🇮🇱Be'er Sheva, Israel
Investigational Site Number : 3760004
🇮🇱Jerusalem, Israel
Investigational Site Number : 3760003
🇮🇱Petah Tikva, Israel
Investigational Site Number : 3760007
🇮🇱Ramat Hasharon, Israel
Investigational Site Number : 3760001
🇮🇱Rehovot, Israel
Ospedale Maggiore Policlinico Milano-Site Number : 3800002
🇮🇹Milan, Milano, Italy
Azienda Ospedaliera di Padova-Site Number : 3800004
🇮🇹Padova, Veneto, Italy
Ospedale di Cisanello-Site Number : 3800003
🇮🇹Pisa, Italy
Investigational Site Number : 6160005
🇵🇱Wroclaw, Dolnoslaskie, Poland
Investigational Site Number : 6160001
🇵🇱Krakow, Malopolskie, Poland
Investigational Site Number : 6160002
🇵🇱Warsaw, Mazowieckie, Poland
Investigational Site Number : 6160004
🇵🇱Poznan, Wielkopolskie, Poland
Investigational Site Number : 7030001
🇸🇰Košice, Slovakia
Investigational Site Number : 7030003
🇸🇰Nitra, Slovakia
Investigational Site Number : 7030004
🇸🇰Šahy, Slovakia
Investigational Site Number : 7240006
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number : 7240009
🇪🇸Chiclana de La Frontera, Cádiz, Spain
Investigational Site Number : 7240002
🇪🇸Seville, Sevilla, Spain
Investigational Site Number : 7240007
🇪🇸Madrid, Spain
Investigational Site Number : 7240003
🇪🇸Madrid, Spain
Investigational Site Number : 7240004
🇪🇸Málaga, Spain
Investigational Site Number : 7240008
🇪🇸Sevilla, Spain
Investigational Site Number : 7522001
🇸🇪Linköping, Sweden
Investigational Site Number : 7521001
🇸🇪Mölndal, Sweden
Investigational Site Number : 7520003
🇸🇪Stockholm, Sweden
Investigational Site Number : 7520001
🇸🇪Uppsala, Sweden
Investigational Site Number : 7920001
🇹🇷Akdeniz, Turkey
Investigational Site Number : 7920004
🇹🇷Antalya, Turkey
Investigational Site Number : 7920006
🇹🇷Istanbul, Turkey
Investigational Site Number : 7920005
🇹🇷Sanliurfa, Turkey
Investigational Site Number : 7920002
🇹🇷Zonguldak, Turkey
Investigational Site Number : 8260001
🇬🇧Oxford, Oxfordshire, United Kingdom
Investigational Site Number : 8260002
🇬🇧Sheffield, United Kingdom