Clinical trial NCT06557772: A Phase 2a/b Study of the Efficacy and Safety of Subcutaneous Amlitelimab in Adults With Nonresponsive Celiac Disease
Official title: A Phase 2a/b, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Investigate the Efficacy and Safety of Subcutaneous Amlitelimab in Adult Patients With Nonresponsive Celiac Disease as an Adjunct to a Gluten-free Diet
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Coeliac Disease
Celiac Disease
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2024-08-16
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

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.

Primary outcomes:
measure: Change in Villus Height to Crypt Depth Ratio (Vh:Cd) from baseline to Week 28
timeFrame: Baseline to Week 28
Secondary outcomes:
measure: Change in Celiac Disease Symptom Diary (CDSD) Gastrointestinal (GI) symptom severity score
timeFrame: Baseline to Week 28
measure: 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
timeFrame: Baseline to Week 168
measure: 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
timeFrame: Baseline to Week 168
measure: Percentage of participants discontinued from study treatment due to TEAEs during the placebo-controlled treatment period and the long-term extension
timeFrame: Baseline to Week 168
measure: Serum amlitelimab concentrations measured at prespecified timepoints
timeFrame: Baseline to Week 168
measure: Incidence of antidrug antibodies (ADAs) of amlitelimab
timeFrame: Baseline to Week 168
Other outcomes:
Locations:
city: Arcadia
country: United States
facility: FOMAT Medical Research - inSite Digestive Health Care - Arcadia- Site Number : 8400052
state: California
city: Camarillo
country: United States
facility: Ventura County Gastroenterology Medical Group- Site Number : 8400010
state: California
city: Lancaster
country: United States
facility: Om Research LLC- Site Number : 8400001
state: California
city: Los Alamitos
country: United States
facility: United Gastroenterologists - Los Alamitos- Site Number : 8400014
state: California
city: Denver
country: United States
facility: Advanced Research Institute - Denver- Site Number : 8400048
state: Colorado
city: Miami Lakes
country: United States
facility: Wellness Clinical Research - Miami Lakes- Site Number : 8400040
state: Florida
city: Orlando
country: United States
facility: Center for Digestive Health- Site Number : 8400013
state: Florida
city: Tampa
country: United States
facility: GCP Clinical Research- Site Number : 8400007
state: Florida
city: Boise
country: United States
facility: Treasure Valley Medical Research- Site Number : 8400006
state: Idaho
city: Hutchinson
country: United States
facility: Hutchinson Clinic- Site Number : 8400020
state: Kansas
city: Boston
country: United States
facility: Boston Specialists- Site Number : 8400051
state: Massachusetts
city: Pittsfield
country: United States
facility: Berkshire Medical Center, Inc.- Site Number : 8400017
state: Massachusetts
city: Wyoming
country: United States
facility: Gastroenterology Associates of Western Michigan - Wyoming- Site Number : 8400004
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Hospital Rochester- Site Number : 8400049
state: Minnesota
city: Reno
country: United States
facility: Advanced Research Institute- Site Number : 8400036
state: Nevada
city: East Orange
country: United States
facility: Sanmora Bespoke Clinical Research Solutions- Site Number : 8400015
state: New Jersey
city: Raleigh
country: United States
facility: M3 Wake Research- Site Number : 8400008
state: North Carolina
city: East Greenwich
country: United States
facility: Velocity Clinical Research - Providence- Site Number : 8400002
state: Rhode Island
city: Chattanooga
country: United States
facility: ClinSearch - Chattanooga - Shallowford Road- Site Number : 8400012
state: Tennessee
city: Nashville
country: United States
facility: Quality Medical Research- Site Number : 8400018
state: Tennessee
city: Houston
country: United States
facility: MedCare Pharma- Site Number : 8400016
state: Texas
city: Pearland
country: United States
facility: LinQ Research, LLC- Site Number : 8400028
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research - Tomball- Site Number : 8400042
state: Texas
city: Ogden
country: United States
facility: Advanced Research Institute - Odgen- Site Number : 8400044
state: Utah
city: West Jordan
country: United States
facility: Velocity Clinical Research - Salt Lake City- Site Number : 8400023
state: Utah
city: Richmond
country: United States
facility: Clinical Research Partners - Richmond - Forest Avenue- Site Number : 8400011
state: Virginia
city: Quilmes
country: Argentina
facility: Investigational Site Number : 0320010
state: Buenos Aires
city: San Isidro
country: Argentina
facility: Investigational Site Number : 0320008
state: Buenos Aires
city: Rosario
country: Argentina
facility: Investigational Site Number : 0320005
state: Santa Fe
city: San Miguel de Tucumán
country: Argentina
facility: Investigational Site Number : 0320002
state: Tucumán
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320007
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320012
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320001
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320009
city: Córdoba
country: Argentina
facility: Investigational Site Number : 0320003
city: Sydney
country: Australia
facility: Investigational Site Number : 0360002
state: New South Wales
city: Mackay
country: Australia
facility: Investigational Site Number : 0360001
state: Queensland
city: Melbourne
country: Australia
facility: Investigational Site Number : 0360005
state: Victoria
city: Brussels
country: Belgium
facility: Investigational Site Number : 0560002
city: Leuven
country: Belgium
facility: Investigational Site Number : 0560001
city: Salvador
country: Brazil
facility: Hospital Sao Rafael- Site Number : 0760005
state: Bahia
city: Salvador
country: Brazil
facility: Centro de Pesquisas da Clínica IBIS- Site Number : 0760006
state: Bahia
city: Brasília
country: Brazil
facility: Chronos Pesquisa Clínica- Site Number : 0760002
state: Distrito Federal
city: Porto Alegre
country: Brazil
facility: Hospital Moinhos de Vento- Site Number : 0760004
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas da PUCRS - Porto Alegre - Avenida Ipiranga- Site Number : 0760001
state: Rio Grande Do Sul
city: Santo Andre
country: Brazil
facility: Praxis Pesquisa Medica- Site Number : 0760008
state: São Paulo
city: Vancouver
country: Canada
facility: Investigational Site Number : 1240001
state: British Columbia
city: Victoria
country: Canada
facility: Investigational Site Number : 1240002
state: British Columbia
city: Concepción
country: Chile
facility: Investigational Site Number : 1520006
state: Biobío
city: Talcahuano
country: Chile
facility: Investigational Site Number : 1520005
state: Biobío
city: Santiago
country: Chile
facility: Investigational Site Number : 1520007
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520004
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520001
state: Reg Metropolitana De Santiago
city: Brno
country: Czechia
facility: Investigational Site Number : 2030002
city: Havířov
country: Czechia
facility: Investigational Site Number : 2030006
city: Klatovy
country: Czechia
facility: Investigational Site Number : 2030005
city: Prague
country: Czechia
facility: Investigational Site Number : 2030001
city: Prague
country: Czechia
facility: Investigational Site Number : 2030003
city: Helsinki
country: Finland
facility: Investigational Site Number : 2460002
city: Tampere
country: Finland
facility: Investigational Site Number : 2460003
city: Turku
country: Finland
facility: Investigational Site Number : 2460001
city: Nice
country: France
facility: Investigational Site Number : 2500002
city: Paris
country: France
facility: Investigational Site Number : 2500001
city: Berlin
country: Germany
facility: Investigational Site Number : 2760004
city: Halle
country: Germany
facility: Investigational Site Number : 2760001
city: Mainz
country: Germany
facility: Investigational Site Number : 2760002
city: Athens
country: Greece
facility: Investigational Site Number : 3000001
city: Athens
country: Greece
facility: Investigational Site Number : 3000002
city: Afula
country: Israel
facility: Investigational Site Number : 3760002
city: Be'er Sheva
country: Israel
facility: Investigational Site Number : 3760006
city: Jerusalem
country: Israel
facility: Investigational Site Number : 3760004
city: Petah Tikva
country: Israel
facility: Investigational Site Number : 3760003
city: Ramat Hasharon
country: Israel
facility: Investigational Site Number : 3760007
city: Rehovot
country: Israel
facility: Investigational Site Number : 3760001
city: Milan
country: Italy
facility: Ospedale Maggiore Policlinico Milano-Site Number : 3800002
state: Milano
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova-Site Number : 3800004
state: Veneto
city: Pisa
country: Italy
facility: Ospedale di Cisanello-Site Number : 3800003
city: Amsterdam
country: Netherlands
facility: Investigational Site Number : 5280001
city: Wroclaw
country: Poland
facility: Investigational Site Number : 6160005
state: Dolnoslaskie
city: Krakow
country: Poland
facility: Investigational Site Number : 6160001
state: Malopolskie
city: Warsaw
country: Poland
facility: Investigational Site Number : 6160002
state: Mazowieckie
city: Poznan
country: Poland
facility: Investigational Site Number : 6160004
state: Wielkopolskie
city: Košice
country: Slovakia
facility: Investigational Site Number : 7030001
city: Nitra
country: Slovakia
facility: Investigational Site Number : 7030003
city: Šahy
country: Slovakia
facility: Investigational Site Number : 7030004
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240006
state: Barcelona [Barcelona]
city: Chiclana de La Frontera
country: Spain
facility: Investigational Site Number : 7240009
state: Cádiz
city: Seville
country: Spain
facility: Investigational Site Number : 7240002
state: Sevilla
city: Madrid
country: Spain
facility: Investigational Site Number : 7240007
city: Madrid
country: Spain
facility: Investigational Site Number : 7240003
city: Málaga
country: Spain
facility: Investigational Site Number : 7240004
city: Sevilla
country: Spain
facility: Investigational Site Number : 7240008
city: Linköping
country: Sweden
facility: Investigational Site Number : 7522001
city: Mölndal
country: Sweden
facility: Investigational Site Number : 7521001
city: Stockholm
country: Sweden
facility: Investigational Site Number : 7520003
city: Uppsala
country: Sweden
facility: Investigational Site Number : 7520001
city: Akdeniz
country: Turkey
facility: Investigational Site Number : 7920001
city: Antalya
country: Turkey
facility: Investigational Site Number : 7920004
city: Gaziantep
country: Turkey
facility: Investigational Site Number : 7920003
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920006
city: Sanliurfa
country: Turkey
facility: Investigational Site Number : 7920005
city: Zonguldak
country: Turkey
facility: Investigational Site Number : 7920002
city: Oxford
country: United Kingdom
facility: Investigational Site Number : 8260001
state: Oxfordshire
city: Sheffield
country: United Kingdom
facility: Investigational Site Number : 8260002
Study officials:
References: