Clinical trial NCT05660109: A Study to Assess the Safety of TPM502 in Adults With Celiac Disease
Official title: A Double-blind, Randomized, Placebo-controlled, Phase 2a Study to Evaluate the Safety, Tolerability, and Pharmacodynamic (PD) Effects of Two Infusions of Escalating Doses of TPM502 in Adults Diagnosed With Celiac Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Celiac Disease
Keywords: celiac disease
tolerance
Lead sponsor: Topas Therapeutics GmbH
Sponsor class: INDUSTRY
First posted: 2022-12-21
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn about the safety and the pharmacodynamic (PD) effects of TPM502 in adults with celiac disease. The main questions it aims to answer are:

* if TPM502 is safe and well tolerated
* if TPM502 can induce modifications in parameters indicating that it may induce tolerance to gluten

Participants will:

* undergo 1-day gluten challenge during screening and after administration of TPM502 or placebo.
* receive 2 infusions of TPM502 or placebo, 2 weeks apart

Detailed description: This is a multi center, double-blind, randomized, placebo-controlled Phase 2a study to evaluate the safety, tolerability, and PD effects of two infusions of TPM502 in adult patients diagnosed with CeD.

The patient´s participation in the study comprises 3 phases: screening period, treatment period and follow-up period.

Patients fulfilling the eligibility criteria will be randomized to receive two infusions of TMP502 (or placebo) at the same dose level. Patients will undergo a second GC one week after the second infusion of TPM502.

The study includes 4 cohorts of patients, each cohort will receive escalating doses of TPM502 (or placebo). Upon completion of the 3rd cohort, a lower dose can be investigated, if deemed relevant.

Eligibility criteria: Inclusion Criteria:

* Availability of a documented biopsy-confirmed diagnosis of CeD OR documented tissue transglutaminase \>10x ULN and documented positive IgA anti-endomysial antibody (EMA) at time of CeD diagnosis (as per local guidelines)
* Serum anti-tissue transglutaminase 2 immunoglobin A antibodies within normal range (i.e., \<15 U/mL) at screening
* Serum IL-2 levels (AUC1-6h) above a pre-defined threshold following the GC at screening
* Patients must have been on GFD for ≥ 6 months
* Patients must have well-controlled CeD, defined as mild or with no ongoing signs or symptoms felt to be related to active CeD, as per investigator's assessment
* HLA-DQ2.5 positive

Exclusion Criteria:

* Known or suspected refractory CeD (refractory CeD type I or II)
* Known intolerable symptoms following previous GCs, as per investigator's assessment
* HLA DQ8 positive
* Any active gastrointestinal disease such as gastroesophageal reflux disease, esophagitis or peptic ulcer, microscopic colitis, or irritable bowel syndrome, which in the opinion of the investigator might interfere with the assessment of the symptoms related to CeD
* Known history of or active Crohn's disease, ulcerative colitis, or ulcerative jejunitis
* Known wheat allergy
* Known hypersensitivity to i.v. iron preparations or any other excipients present in the reconstituted TPM502 or placebo

Primary outcomes:
measure: Incidence, severity, causality, and outcomes of treatment-emergent adverse events
timeFrame: throughout the study, on average 43 days
Secondary outcomes:
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Brisbane
country: Australia
facility: Wesley Research Institute
city: Turku
country: Finland
facility: CRST Oy
city: Berlin
country: Germany
facility: Charite' Hospital
city: Leiden
country: Netherlands
facility: Centre for Human Drug Research
city: Oslo
country: Norway
facility: Oslo University Hospital HF - Rikshospitalet
city: Tromsø
country: Norway
facility: University Hospital of North-Norway
city: Uppsala
country: Sweden
facility: Clinical Trial Consultants, Uppsala University
Study officials:
affiliation: Oslo University Hospital
name: Knut Lundin, MD
role: PRINCIPAL_INVESTIGATOR
References: