Phase 2
N=34
Study of the Safety, Pharmacodynamics, Efficacy, and PK of TIMP-GLIA in Subjects With Celiac Disease
Celiac Disease
Bottom Line
View on ClinicalTrials.gov: NCT03738475 ↗Enrolled (actual)
34
Serious AEs
0.0%
Results posted
Aug 2020
Primary outcome: Primary: Change From Baseline in Interferon-Gamma Spot Forming Units (IFN-gamma SFUs) in a Gliadin-specific Enzyme-linked Immunospot (ELISpot) at Day 20 — 3.08; 1.98; 2.01; 17.57 SFUs/10^6 cells PBMC — p=0.0056
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- TIMP-GLIA (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Takeda
- Primary completion
- Jun 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Interferon-Gamma Spot Forming Units (IFN-gamma SFUs) in a Gliadin-specific Enzyme-linked Immunospot (ELISpot) at Day 20 |
3.08; 1.98; 2.01; 17.57 | 0.0056 sig |
| SECONDARY Change From Baseline in Gliadin-specific T Cell Proliferation by Enzyme-linked Immunosorbent Assay (ELISA) at Day 20 |
0.87; 1.00; 0.05; 0.00 | — |
| SECONDARY Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 |
1.44; 1.70; -0.43; -0.01; 1.24; 2.68 | — |
| SECONDARY Change From Baseline in Gut-Homing CD4, CD8 and Gamma Delta T-cells by Mass Cytometry (CyTOF) at Day 20 |
0.21; 0.18; 0.69; 3.64; 0.19; 0.16 | — |
| SECONDARY Change From Baseline in Ratio of Villus Height to Crypt Depth (Vh:Cd) at Day 29 |
2.82; 3.01; -0.18; -0.63 | 0.0799 |
| SECONDARY Percentage of Participants With Greater Than or Equal to (>=) 0.4 Decrease in Vh:Cd at Day 29 |
23.1; 53.3 | — |
| SECONDARY Change From Baseline in Number of Intestinal Intraepithelial Lymphocytes (IELs) at Day 29 |
39.62; 34.53; 28.62; 35.00 | 0.2890 |
| SECONDARY Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment |
11; 13; 3; 4; 2; 1 | — |
| SECONDARY Plasma Concentrations of TIMP-GLIA |
13.06; 684.54; 383.46 | — |
| SECONDARY Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) |
16; 18; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Change From Baseline in Vital Signs |
0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Change From Baseline in Hematology or Serum Chemistry Laboratory Values |
0; 0 | — |
| SECONDARY Change From Baseline in Deamidated Gliadin Peptide Immunoglobulin G (DGP-IgG) Antibodies at Days 8, 15, 20, 29, and 35 |
7.9; 5.9; 4.3; -0.6; 27.8; 0.3 | — |
| SECONDARY Change From Baseline in Serum Complement Levels of C3a and SC5B-9 at Days 2, 8, 9, and 15 |
1024.0; 1069.9; -144.6; 112.3; 244.7; -115.3 | — |
| SECONDARY Change From Baseline in Serum Complement Levels of C5a at Days 2, 8, 9, and 15 |
9.290; 7.267; 0.763; -0.067; 8.373; 0.082 | — |
| SECONDARY Change From Baseline in Serum Complement Levels of C1q Binding at Days 15, 20, 29, and 35 |
3.65; 4.53; 0.64; 0.21; 0.88; -0.15 | — |
| SECONDARY Change From Baseline in Serum Cytokines (IFN-γ, IL 1-β, IL-2, IL-4, IL-6, IL-8 , IL-10, IL-12p70, and TNF-Alpha) at Days 2, 8, 9, and 15 |
7.375; 4.592; 9.871; -0.179; -2.374; 5.245 | — |
Summary
Subjects enrolled in this study will be evaluated for immune responses and histological changes in the small bowel following 2 doses of TIMP-GLIA or placebo and a 14-day oral gluten challenge.
Eligibility Criteria
Key Inclusion Criteria
- Male or nonpregnant female, ages 18 to 70 years inclusive, at Screening Visit.
- Biopsy-confirmed CD (intestinal histology showing villous atrophy).
- Positive for human leukocyte antigen (HLA)-DQ2 or HLA-DQ2/DQ8 - results will be obtained at Screening if unknown or results are not available.
- Self-reported to be on a GFD for at least 6 months prior to Screening and agree to continue GFD throughout study, with the exception of the oral gluten challenge.
Normal or negative celiac serology, at screening, defined as:
- Measurable total serum immunoglobulin A (IgA) AND
- Negative or weak positive tissue transglutaminase (tTG) IgA titer OR
- If IgA deficient, defined by a serum IgA level of 960 µg/day of beclomethasone dipropionate or equivalent]) or other immunosuppressive agents.
- Presence or history of celiac-associated thyroid disease or Type 1 diabetes, regardless of current treatment.
Data sourced from ClinicalTrials.gov (NCT03738475). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.