A placebo-controlled study to evaluate the safety, tolerability, biochemical and physiologic effects of two infusions of escalating doses of TPM502 in adults diagnosed with celiac disease
- Conditions
- Coeliac diseaseTherapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2022-001656-41-NL
- Lead Sponsor
- Topas Therapeutics GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 42
1. Availability of a documented biopsy-confirmed diagnosis of CeD OR documented tissue transglutaminase >10x upper limit of normal (ULN) and documented positive immunoglobulin A (IgA) anti-endomysial antibody (EMA) at time of CeD diagnosis (as per local guidelines)
2. Serum anti-tissue transglutaminase 2 immunoglobin A antibodies within normal range at screening
3. Serum IL-2 levels (AUC1-6h) > 2x AUC1-6h at the lower level of quantification (LLOQ) (i.e., 8x LLOQ) following the GC at screening
4. Patients must have been on gluten-free diet (GFD) for = 6 months
5. 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
6. Human leukocyte antigen (HLA)-DQ2.5 positive (homozygous and heterozygous) but HLA-DQ8 and HLA-DQ2.2 negative
7. Full SARS-Cov2 vaccination, as defined by specific national guidance.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 36
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Known or suspected refractory CeD (refractory CeD type I or II)
2. Known intolerable symptoms following previous GCs, as per investigator`s assessment
3. Treatment with systemic immunosuppressants (e.g., glucocorticoids), ongoing or administered in the 12 weeks preceding the first investigational medicinal product (IMP) administration
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the safety and tolerability of two i.v. infusions of escalating doses of TPM502 in CeD patients.;Secondary Objective: • To identify PD effects consistent with the induction of antigen-specific immune tolerance following the administration of TPM502<br>• To describe the severity of gastrointestinal (GI) symptoms following the administration of TPM502 and a GC<br>• To determine TPM502 PK<br><br>Exploratory objectives:<br>• To assess ex vivo gluten-specific T cell responses following TPM502 administration<br>• To assess changes in T cell phenotypes upon TPM502 treatment<br>• To further investigate the mechanism of action of TPM502.<br>;Primary end point(s): Incidence, severity, causality and outcomes of TEAEs (serious and non-serious), including hypersensitivity reactions, CRS, hepatotoxicity and other AEs suggestive of these conditions.;Timepoint(s) of evaluation of this end point: Continuous monitoring, all time points.<br>
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Ratio Interleukin 2 (IL-2) after GC post-TPM502 treatment/IL-2 after GC at screening” compared to the placebo group <br>• Modified Celiac disease patient-reported outcome (CeD PRO®) and GloSS (Global Symptom Survey) 1 hour before and then hourly up to 6 hours post GC/ TPM502 compared to placebo<br>• Maximum observed plasma concentration after dosing (Cmax), area under the plasma concentration-time curve from time zero to the time of the last quantifiable sample (area under the curve (AUC) 0-last<br>;Timepoint(s) of evaluation of this end point: Continuous monitoring, all time points.<br>