A Phase 2a/b study of the efficacy and safety of subcutaneous amlitelimab in adults with non-responsive celiac disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

15 Oct 2024 → ongoing

Decision date (initial)

2024-09-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-511213-38-00

WHO UTN

U1111-1298-7193

ClinicalTrials.gov

NCT06557772

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Dose response, Pharmacokinetic

To evaluate the efficacy of amlitelimab vs placebo to improve or attenuate gluten-induced changes in intestinal mucosa in participants with non-responsive celiac disease (NRCD) in two independent conditions, as an adjunct to a gluten-free diet (gluten-free product population) and with background gluten exposure (SIGE population)

Secondary objectives 4

1. To evaluate the effect of amlitelimab vs placebo to control the severity of symptoms of celiac disease in participants with NRCD
2. To assess the safety and tolerability of amlitelimab treatment in participants with NRCD
3. To characterize the pharmacokinetic (PK) profile of amlitelimab administered by subcutaneous (SC) injection in participants with NRCD
4. To characterize immunogenicity of amlitelimab administered by SC injection in participants with NRCD

Conditions and MedDRA coding

Coeliac disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Participants must be 18 to 75 years of age inclusive, at the time of signing the informed consent.
2. Participants with physician-diagnosed celiac disease with documented history of biopsy-proven celiac disease confirmed by medical records or physician statement.
3. 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.
4. Participants have an adequate comprehension of a GFD as assessed by the Investigator.
5. Participants willing to undergo all assessments in the protocol, including 2 esophagogastroduodenoscopies with duodenal biopsies.
6. Participants who completed CDSD with ≥ 75% compliance from screening until randomization.
7. 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 14

1. 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.
2. 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.
3. 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.
4. 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.
5. 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).
6. 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.
7. 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).
8. History of solid organ or stem cell transplant.
9. 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).
10. 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.
11. Any ongoing treatment with systemic immunosuppressants, systemic corticosteroids, or use of oral budesonide in the 12 weeks before screening.
12. 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.
13. Concurrent participation in any other clinical study, including non-interventional studies.
14. Prior administration of investigational agents to treat celiac disease within 5 half-lives of any agent, or one year from any tolerogenic agent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 6

1. Change in Celiac Disease Symptom Diary (CDSD) Gastrointestinal (GI) symptom severity score
2. 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
3. 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
4. Percentage of participants discontinued from study treatment due to TEAEs during the placebo-controlled treatment period and the long-term extension
5. Serum amlitelimab concentrations measured at prespecified timepoints
6. Incidence of anti-drug antibodies (ADAs) of amlitelimab

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 26

Locations

12 EU/EEA countries · 45 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 348 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

15 submissions — initial application plus substantial / non-substantial modifications