A Phase 2a Trial to Characterize the Efficacy and Safety of TEV-53408 in Adults with Celiac Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Teva Branded Pharmaceutical Products R&D LLC

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 Aug 2025 → ongoing

Decision date (initial)

2025-04-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Teva Branded Pharmaceutical Products R&D LLC

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary efficacy objective of the trial is to assess the ability of a single dose of TEV-53408 administered sc to attenuate gluten-induced enteropathy in adults with celiac disease.
The primary safety objective of the trial is to assess the safety of a single dose of TEV-53408 administered sc in adults with celiac disease up to week 28.

Secondary objectives 1

1. To further assess the efficacy of a single dose of TEV-53408 administered sc in adults with celiac disease.

Conditions and MedDRA coding

Celiac Disease

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to patient level data and related study documents including the study protocol and the statistical analysis plan. Requests will be reviewed for scientific merit, product approval status, and conflicts of interest. Patient level data will be de-identified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Please visit www.clinicalstudydatarequest.com to make your request.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. a. Male or female (assigned sex at birth) ≥18 to <65 years of age, inclusive, at the time of signing the informed consent.
2. b. Diagnosis of celiac disease at least 12 months prior to screening (documentation required at screening): − Participant has documentation of EGD confirming celiac disease and positive antibodies, or − If the participant is <30 years of age and a biopsy was not performed at the time of the celiac diagnosis, the participant had met the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) criteria for diagnosis.
3. c. On a gluten-free diet for at least 12 months prior to screening, as determined by the investigator through participant interview.
4. d. tTg IgA <2 U/mL at screening.
5. e. Minimal enteropathy as determined by Vh:Cd ≥2.0 on a duodenal biopsy (EGD) performed during screening period.
6. f. No moderate or severe gastrointestinal symptoms attributable to celiac disease at Screening (visit 1) based on the Symptom Screening Tool.
7. g. Positive at screening for HLA DQ2 or HLA DQ8.
8. h. Body mass index >18.5 to 40 kg/m2 (inclusive).
9. i. Women of non-childbearing potential should be: − congenitally or surgically sterile (documented hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) as assessed by a physician, or − 1-year postmenopausal (no menses for at least 12 months without an alternative medical cause, plus either a concentration of follicle-stimulating hormone [FSH] within the postmenopausal range [an increased concentration of FSH of more than 35 IU/L] in women not using hormonal contraception/hormonal replacement therapy [HRT], or medical documentation of menopause for women on HRT).
10. j. Women of childbearing potential (WOCBP) must have a negative β-human chorionic gonadotropin (HCG) test result and practice a highly effective method of birth control prior to IMP administration and for the duration of trial participation, or for 5 half-lives of TEV-53408 (28 weeks) after IMP administration, whichever is longer.
11. k. Women must not be pregnant, lactating, breastfeeding, or planning pregnancy during the trial period.
12. l. Male participants (including vasectomized) with WOCBP partners (whether pregnant or not) must use condoms and also agree not to donate sperm after IMP administration and for the duration of trial participation, or for 5 half-lives of TEV-53408 (28 weeks) after IMP administration, whichever is longer.
13. m. Participants should be capable of giving signed informed consent, and willing and able to comply with trial procedures, including duodenal biopsy both during screening and at week 8, maintaining the gluten challenge, and other restrictions.

Exclusion criteria 29

1. a. A diagnosis or suspicion of refractory celiac disease.
2. j. The participant has a history of chronic alcohol or substance abuse disorder within the previous 2 years.
3. k. The participant has an active infection(s) requiring treatment with intravenous (iv) anti-infectives (antibiotics, antivirals, antifungals) within 30 days prior to screening or oral anti-infectives (antibiotics, antivirals, antifungals) within 14 days prior to screening.
4. l. Received or intends to receive any live vaccine within 4 weeks or any non-live vaccine 2 weeks prior to IMP administration. Live vaccines include, but are not limited to, measles, mumps, rubella (MMR combined vaccine), rotavirus, smallpox, chickenpox, yellow fever, and oral polio vaccine.
5. m. An active infection with EBV or CMV, with a confirmed EBV or CMV PCR-based viral DNA level of ≥10000 IU/mL obtained at screening. Note: “Confirmed” is defined by a repeat positive test within 7 days of the reporting of the initial finding.
6. n. A clinically active infection of HPV, VZV, or HSV 1/2 at screening or baseline.
7. o. Active tuberculosis (TB) (as determined by the QuantiFERON® TB Gold Test) or history of untreated latent or active TB. Note: If the QuantiFERON ® TB Gold Test is indeterminate, a second test should be performed through the central laboratory or local. If the second test is positive, the participant is considered to be positive. If the second test is negative, the participant is considered to be negative.
8. p. Positive viral serology at screening: − Hepatitis B: hepatitis B surface antigen (HBsAg) positive or detected sensitivity on the HBV-DNA PCR qualitative test for hepatitis B core total antibody (HBcAb)/hepatitis B surface antibody (HBsAb) positive participants − Hepatitis C: HCV ribonucleic acid (RNA) detectable in any participant with positive anti-HCV antibody (HCVAb) − Human immunodeficiency virus (HIV) Types 1 or 2 Ab (confirmed positive serology test, according to 4th generation serology testing)
9. q. Participant has a history of opportunistic or serious infection that makes the participant an unsuitable candidate for the trial (if the infection is oral herpes simplex or palmoplantar warts, then the participant will be allowed).
10. r. Participant has a known genetic or acquired immune deficiency.
11. s. Participant has a history of disseminated herpes simplex, multidermatomal, ophthalmic, recurrent herpes zoster, or herpes encephalitis.
12. b. History of severe celiac-related symptoms following gluten exposure that require acute medical care or intervention of a health care professional (either inpatient or outpatient) for management, dermatitis herpetiformis, or history of neurological symptoms including ataxia after gluten exposure.
13. t. Any participant that has a chronic or recurrent infection that the investigator believes does not fit any of the above exclusion criteria should be discussed with the medical monitor prior to enrollment in the trial.
14. u. Prior treatment with systemic immune suppressants or modulators including biological agents within the past 2 years for any condition (a brief course of 7 days or less of oral or parenteral corticosteroids for an emergent transient medical condition is allowed if use was >4 weeks prior to screening; up to 2 treatment courses per year).
15. v. Use of angiotensin II receptor blockers (eg, losartan, olmesartan, valsartan) within 4 weeks prior to screening.
16. w. Use of probiotic supplements within 4 weeks prior to randomization (probiotics in food [eg, yogurt] are allowed).
17. x. The participant has any of the following values from laboratory testing at screening (abnormal laboratory tests at the screening visit may be repeated once during the screening period): − aspartate aminotransferase (AST) >3 × upper limit of normal (ULN) − alanine aminotransferase (ALT) >3 × ULN − total bilirubin >1.5 × ULN (unless it is known to be secondary to Gilbert’s syndrome per the participant’s medical history) − creatine phosphokinase (CPK) >2.5 × ULN − lymphocyte count <1000 cells/μL − NK cell percentage below 4% of total lymphocytes. NK cell percentage is calculated as the ratio of CD56+ cells divided by the total lymphocyte count (CD45+ cells from T cell, B cell, and natural killer cell [TBNK] cell assay). If the total lymphocyte count is below the normal range, the denominator for the calculation will be the LLN for the lymphocyte count.
18. y. The participant has any other laboratory or physical examination findings or clinically significant electrocardiogram (ECG) result that might place the participant at an unacceptable risk for participation in this trial in the opinion of the investigator.
19. c. Any other gastrointestinal disease or condition that may interfere with the assessment of celiac disease, such as irritable bowel syndrome, lactose intolerance, uncontrolled gastroesophageal reflux disease, ulcerative colitis, Crohn’s disease, or microscopic colitis. In addition, participants who have evidence on screening endoscopy of greater than Grade A esophagitis, eosinophilic esophagitis, or active peptic ulcer are excluded.
20. d. Current or history of malignancy or treatment of malignancy in the last 5 years, excluding treated basal cell carcinoma.
21. e. Pregnant or lactating woman, or plans to become pregnant during the trial; any man who is considering fathering a child or donating sperm during the trial.
22. f. The participant is currently participating in, or has participated in another trial of an IMP (or a medical device) within the previous 30 days or 5 half-lives of the IMP (whichever is longer).
23. g. The participant has previously been randomized within this trial or has participated previously in a trial with TEV-53408 or another anti–IL-15 therapy. In addition, participants who received any other immunotherapy for celiac disease within 2 years prior to screening are excluded.
24. h. Known hypersensitivity or idiosyncratic reaction to the IMP, its related compounds, or to any metabolites or any compound listed as being present in a trial formulation or other IMP; history of anaphylactic reactions to protein therapeutics or known hypersensitivity to any ingredients listed in the label of the daily gluten dose that is to be consumed during the gluten challenge in this trial.
25. i. Donated or received any blood or blood products (eg, WBCs, platelets) within the 60 days prior to screening or has donated blood or blood products on 2 or more occasions within the 6 months prior to IMP administration, or donated plasma within 7 days before the screening visit or has planned donations during the trial. The minimum reference volume of whole blood lost or donated is 500 mL.
26. z. The participant is an employee of the sponsor or the site or a relative of an employee at the site conducting the trial.
27. aa. Prisoners or participants who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious disease) illness.
28. bb. Legal or mental incapacitation, or inability to understand and comply with the requirements of the trial.
29. cc. Participants incapable of giving written informed consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Change from baseline in villous atrophy, as assessed by Vh:Cd, at week 8.
2. Incidence of treatment-emergent adverse events up to week 28.
3. Incidence of serious adverse events up to week 28.
4. Incidence of PDAESIs up to week 28.
5. Incidence of early discontinuations during the treatment period (up to week 28) due to an adverse event.

Secondary endpoints 2

1. Change from baseline in IEL density at week 8.
2. Change from baseline in a composite measure of VCIEL at week 8.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Teva Branded Pharmaceutical Products R&D LLC

Sponsor organisation

Teva Branded Pharmaceutical Products R&D LLC

Address

145 Brandywine Parkway

City

West Chester

Postcode

19380-4245

Country

United States

Scientific contact point

Organisation

Teva Branded Pharmaceutical Products R&D LLC

Contact name

Medical Information

Public contact point

Organisation

Teva Branded Pharmaceutical Products R&D LLC

Contact name

Medical Information

Third parties 1

Locations

1 EU/EEA country · 2 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 14 files

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

Application history

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