A Phase 2a/b Study of the Efficacy and Safety of Subcutaneous Amlitelimab in Adults With Nonresponsive Celiac Disease

NCT06557772 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: DRI179632024-511213-38U1111-1298-7193
• Study Type: interventional
• Target: 229
• Locations: 21 countries
• Sites: 118

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.

Conditions

Coeliac Disease; Celiac Disease

Outcome Measures

Primary Outcomes (1)

• Change in Villus Height to Crypt Depth Ratio (Vh:Cd) from baseline to Week 28

  Change in Vh:Cd ratio.

  Baseline to Week 28

Secondary Outcomes (6)

• Change in Celiac Disease Symptom Diary (CDSD) Gastrointestinal (GI) symptom severity score

  Baseline to Week 28

• 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

Study Arms (6)

Amlitelimab dose 1 + Gluten-free product (GFP)

EXPERIMENTAL

Amlitelimab SC as per protocol + GFP

Drug: Amlitelimab; Dietary Supplement: Gluten-free product (GFP)

Amlitelimab dose 2 + GFP

EXPERIMENTAL

Amlitelimab SC as per protocol + GFP

Drug: Amlitelimab; Dietary Supplement: Gluten-free product (GFP)

Amlitelimab dose 3 + GFP

EXPERIMENTAL

Amlitelimab SC as per protocol + GFP

Drug: Amlitelimab; Dietary Supplement: Gluten-free product (GFP)

Amlitelimab dose 1 + SIGE

EXPERIMENTAL

Amlitelimab SC as per protocol + SIGE

Drug: Amlitelimab; Dietary Supplement: SIGE

Placebo + GFP

PLACEBO COMPARATOR

Placebo SC as per protocol + GFP

Drug: Placebo; Dietary Supplement: Gluten-free product (GFP)

Placebo + SIGE

PLACEBO COMPARATOR

Placebo SC as per protocol + SIGE

Drug: Placebo; Dietary Supplement: SIGE

Interventions

Gluten-free product (GFP) DIETARY_SUPPLEMENT

Pharmaceutical form: Capsule Route of administration: Oral

Amlitelimab dose 1 + Gluten-free product (GFP); Amlitelimab dose 2 + GFP; Amlitelimab dose 3 + GFP; Placebo + GFP

Amlitelimab DRUG

Pharmaceutical form: Injection solution Route of administration: SC injection

Also known as: SAR445229

Amlitelimab dose 1 + Gluten-free product (GFP); Amlitelimab dose 1 + SIGE; Amlitelimab dose 2 + GFP; Amlitelimab dose 3 + GFP

Placebo DRUG

Pharmaceutical form: Injection solution Route of administration: SC injection

Placebo + GFP; Placebo + SIGE

SIGE DIETARY_SUPPLEMENT

Pharmaceutical form: Capsule Route of administration: Oral

Amlitelimab dose 1 + SIGE; Placebo + SIGE

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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 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.
• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (118)

One of a Kind Clinical Research Center - Scottsdale- Site Number : 8400055

Scottsdale, Arizona, 85253, United States

Location

FOMAT Medical Research - inSite Digestive Health Care - Arcadia- Site Number : 8400052

Arcadia, California, 91006, United States

Location

Om Research- Site Number : 8400001

Lancaster, California, 93534, United States

Location

United Medical Doctors - Los Alamitos- Site Number : 8400014

Los Alamitos, California, 90720, United States

Location

Om Research- Site Number : 8400010

Oxnard, California, 93030, United States

Location

Advanced Research Institute - Denver- Site Number : 8400048

Denver, Colorado, 80218, United States

Location

Wellness Clinical Research - Miami Lakes - 8181 Northwest 154th Street- Site Number : 8400040

Miami Lakes, Florida, 33016, United States

Location

Center for Digestive Health- Site Number : 8400013

Orlando, Florida, 32803, United States

Location

GCP Clinical Research- Site Number : 8400007

Tampa, Florida, 33609, United States

Location

Treasure Valley Medical Research- Site Number : 8400006

Boise, Idaho, 83706, United States

Location

Hutchinson Clinic- Site Number : 8400020

Hutchinson, Kansas, 67502, United States

Location

University of Kansas Medical Center- Site Number : 8400041

Kansas City, Kansas, 66160, United States

Location

Boston Specialists- Site Number : 8400051

Boston, Massachusetts, 02111, United States

Location

Berkshire Medical Center- Site Number : 8400017

Pittsfield, Massachusetts, 01201, United States

Location

Gastroenterology Associates of Western Michigan - Wyoming- Site Number : 8400004

Wyoming, Michigan, 49519, United States

Location

Mayo Clinic in Rochester - Minnesota- Site Number : 8400049

Rochester, Minnesota, 55905, United States

Location

Washington University- Site Number : 8400025

St Louis, Missouri, 63110, United States

Location

Advanced Research Institute - Reno- Site Number : 8400036

Reno, Nevada, 89511, United States

Location

Sanmora Bespoke Clinical Research Solutions- Site Number : 8400015

East Orange, New Jersey, 07018, United States

Location

Allied Digestive Health - Middlesex Monmouth Gastroenterology- Site Number : 8400053

Freehold, New Jersey, 07728, United States

Location

M3 Wake Research- Site Number : 8400008

Raleigh, North Carolina, 27612, United States

Location

Thomas Jefferson University Hospital- Site Number : 8400056

Philadelphia, Pennsylvania, 19107, United States

Location

Velocity Clinical Research - Providence- Site Number : 8400002

East Greenwich, Rhode Island, 02818, United States

Location

M3 Wake Research - Chattanooga- Site Number : 8400012

Chattanooga, Tennessee, 37421, United States

Location

Quality Medical Research- Site Number : 8400018

Nashville, Tennessee, 37211, United States

Location

Texas Digestive Disease Consultants - Cedar Park- Site Number : 8400030

Cedar Park, Texas, 78613, United States

Location

MedCare Pharma - Houston - Cypress Creek Parkway- Site Number : 8400016

Houston, Texas, 77090, United States

Location

LinQ Research - Smith Ranch Road- Site Number : 8400028

Pearland, Texas, 77584, United States

Location

DM Clinical Research - Tomball- Site Number : 8400042

Tomball, Texas, 77375, United States

Location

Advanced Research Institute - Odgen- Site Number : 8400044

Ogden, Utah, 84405, United States

Location

Advanced Research Institute - Sandy - South 1300 East- Site Number : 8400046

Sandy City, Utah, 84094, United States

Location

Velocity Clinical Research - Salt Lake City- Site Number : 8400023

West Jordan, Utah, 84088, United States

Location

Gastroenterology Associates of Central Virginia- Site Number : 8400057

Lynchburg, Virginia, 24502, United States

Location

Clinical Research Partners - Richmond - Forest Avenue- Site Number : 8400011

Richmond, Virginia, 23220, United States

Location

GI Alliance - Tacoma- Site Number : 8400033

Tacoma, Washington, 98405, United States

Location

Investigational Site Number : 0320010

Quilmes, Buenos Aires, 1878, Argentina

Location

Investigational Site Number : 0320008

San Isidro, Buenos Aires, 1642, Argentina

Location

Investigational Site Number : 0320012

Buenos Aires, Buenos Aires F.D., 1061, Argentina

Location

Investigational Site Number : 0320005

Rosario, Santa Fe Province, 2000, Argentina

Location

Investigational Site Number : 0320002

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

Investigational Site Number : 0320007

Buenos Aires, 1006, Argentina

Location

Investigational Site Number : 0320009

Buenos Aires, 1119, Argentina

Location

Investigational Site Number : 0320001

Buenos Aires, 1128, Argentina

Location

Investigational Site Number : 0320003

Córdoba, 5000, Argentina

Location

Investigational Site Number : 0360002

Sydney, New South Wales, 2560, Australia

Location

Investigational Site Number : 0360001

Mackay, Queensland, 4740, Australia

Location

Investigational Site Number : 0360005

Melbourne, Victoria, 3128, Australia

Location

Investigational Site Number : 0560002

Brussels, 1200, Belgium

Location

Investigational Site Number : 0560001

Leuven, 3000, Belgium

Location

Hospital Sao Rafael- Site Number : 0760005

Salvador, Estado de Bahia, 41253-190, Brazil

Location

Centro de Pesquisas da Clínica IBIS- Site Number : 0760006

Salvador, Estado de Bahia, 41820-020, Brazil

Location

Chronos Pesquisa Clínica- Site Number : 0760002

Brasília, Federal District, 72145-450, Brazil

Location

Hospital Moinhos de Vento- Site Number : 0760004

Porto Alegre, Rio Grande do Sul, 90035-902, Brazil

Location

Hospital São Lucas da PUCRS - Porto Alegre - Avenida Ipiranga- Site Number : 0760001

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Praxis Pesquisas Medicas- Site Number : 0760008

Santo André, São Paulo, 09090-790, Brazil

Location

Investigational Site Number : 1240001

Vancouver, British Columbia, V6Z 2K5, Canada

Location

Investigational Site Number : 1240002

Victoria, British Columbia, V8V 3M9, Canada

Location

Investigational Site Number : 1520007

Santiago, Reg Metropolitana de Santiago, 7510086, Chile

Location

Investigational Site Number : 1520004

Santiago, Reg Metropolitana de Santiago, 7620001, Chile

Location

Investigational Site Number : 1520001

Santiago, Reg Metropolitana de Santiago, 8330034, Chile

Location

Investigational Site Number : 1520008

Santiago, Reg Metropolitana de Santiago, 8331143, Chile

Location

Investigational Site Number : 1520006

Concepción, Región del Biobío, 4070038, Chile

Location

Investigational Site Number : 1520005

Talcahuano, Región del Biobío, 2687000, Chile

Location

Investigational Site Number : 2030002

Brno, 636 00, Czechia

Location

Investigational Site Number : 2030006

Havířov, 736 01, Czechia

Location

Investigational Site Number : 2030005

Klatovy, 339 01, Czechia

Location

Investigational Site Number : 2030001

Prague, 118 33, Czechia

Location

Investigational Site Number : 2030003

Prague, 150 06, Czechia

Location

Investigational Site Number : 2460002

Helsinki, 00180, Finland

Location

Investigational Site Number : 2460003

Helsinki, 00270, Finland

Location

Investigational Site Number : 2460001

Turku, 20520, Finland

Location

Investigational Site Number : 2500002

Nice, 06202, France

Location

Investigational Site Number : 2500001

Paris, 75015, France

Location

Investigational Site Number : 2760006

Berlin, 10117, Germany

Location

Investigational Site Number : 2760004

Berlin, 12203, Germany

Location

Investigational Site Number : 2760001

Halle, 06108, Germany

Location

Investigational Site Number : 2760002

Mainz, 55131, Germany

Location

Investigational Site Number : 3000001

Athens, 106 76, Greece

Location

Investigational Site Number : 3000002

Athens, 115 27, Greece

Location

Investigational Site Number : 3760002

Afula, 1834111, Israel

Location

Investigational Site Number : 3760006

Beersheba, 8457108, Israel

Location

Investigational Site Number : 3760004

Jerusalem, 9103102, Israel

Location

Investigational Site Number : 3760003

Petah Tikva, 4941492, Israel

Location

Investigational Site Number : 3760007

Ramat HaSharon, 4731001, Israel

Location

Investigational Site Number : 3760001

Rehovot, 7610001, Israel

Location

Ospedale Maggiore Policlinico Milano-Site Number : 3800002

Milan, Milano, 20122, Italy

Location

Azienda Ospedaliera di Padova-Site Number : 3800004

Padua, Padova, 35128, Italy

Location

Ospedale di Cisanello-Site Number : 3800003

Pisa, 56124, Italy

Location

Investigational Site Number : 5280001

Amsterdam, 1081 HV, Netherlands

Location

Investigational Site Number : 5280002

Arnhem, 6815 AD, Netherlands

Location

Investigational Site Number : 6160004

Poznan, Greater Poland Voivodeship, 60-529, Poland

Location

Investigational Site Number : 6160001

Krakow, Lesser Poland Voivodeship, 31-501, Poland

Location

Investigational Site Number : 6160005

Wroclaw, Lower Silesian Voivodeship, 50-088, Poland

Location

Investigational Site Number : 6160002

Warsaw, Masovian Voivodeship, 02-507, Poland

Location

Investigational Site Number : 7030001

Košice, 040 13, Slovakia

Location

Investigational Site Number : 7030003

Nitra, 950 01, Slovakia

Location

Investigational Site Number : 7030004

Šahy, 936 01, Slovakia

Location

Investigational Site Number : 7240006

Barcelona, Barcelona [Barcelona], 08035, Spain

Location

Investigational Site Number : 7240009

Chiclana de la Frontera, Cádiz, 11139, Spain

Location

Investigational Site Number : 7240011

Las Palmas de Gran Canaria, Las Palmas, 35010, Spain

Location

Investigational Site Number : 7240002

Seville, Sevilla, 41013, Spain

Location

Investigational Site Number : 7240007

Madrid, 28003, Spain

Location

Investigational Site Number : 7240003

Madrid, 28034, Spain

Location

Investigational Site Number : 7240004

Málaga, 29010, Spain

Location

Investigational Site Number : 7240008

Seville, 41012, Spain

Location

Investigational Site Number : 7240010

Seville, 41012, Spain

Location

Investigational Site Number : 7522001

Linköping, 582 16, Sweden

Location

Investigational Site Number : 7521001

Mölndal, 431 53, Sweden

Location

Investigational Site Number : 7520003

Stockholm, 116 91, Sweden

Location

Investigational Site Number : 7520001

Uppsala, 752 37, Sweden

Location

Investigational Site Number : 7920004

Antalya, 07100, Turkey (Türkiye)

Location

Investigational Site Number : 7920003

Gaziantep, 27310, Turkey (Türkiye)

Location

Investigational Site Number : 7920006

Istanbul, 34899, Turkey (Türkiye)

Location

Investigational Site Number : 7920007

Izmir, 35100, Turkey (Türkiye)

Location

Investigational Site Number : 7920001

Mersin, 33070, Turkey (Türkiye)

Location

Investigational Site Number : 7920005

Sanliurfa, 63290, Turkey (Türkiye)

Location

Investigational Site Number : 8260001

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

Investigational Site Number : 8260002

Sheffield, S5 7AU, United Kingdom

Location

Related Links

• DRI17963 Plain Language Results Summary

MeSH Terms

Conditions

Celiac Disease

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2024
• First Posted: August 16, 2024
• Study Start: August 29, 2024
• Primary Completion (Estimated): August 5, 2026
• Study Completion (Estimated): April 10, 2029
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

CL (6); CZ (5); GR (2); US (35); FR (2); NL (2); AU (3); CA (2); SL (3); BR (6); TU (6); PL (4); DE (4); IL (6); BE (2); FI (3); AR (9); GB (2); IT (3); SE (4); ES (9)