Study of the Safety, Pharmacodynamics, Efficacy, and PK of TIMP-GLIA in Subjects With Celiac Disease
Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT03738475
Collaborator
COUR Pharmaceuticals Development Company, Inc. (Other)
34
8
2
8.3
4.3
0.5
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This study is a randomized, double-blind, placebo-controlled clinical trial to assess the safety, pharmacodynamics, efficacy, and PK, of TIMP-GLIA in subjects with well-controlled celiac disease (CD) following an oral gluten challenge. Subjects aged 18 to 70 years inclusive, with documented history of biopsy-proven confirmed CD, and on a gluten-free diet (GFD) for a minimum of 6 months, will be screened. Subjects who meet all inclusion and no exclusion criteria, and provide written informed consent, will be randomized within 45 days after Screening to receive 2 intravenous (IV) infusions of TIMP-GLIA, 8 mg/kg up to a maximum of 650 mg or placebo (normal saline) in a 1:1 ratio. Treatment with drug or placebo will be followed by 14 days gluten challenge.
Study Design
Study Type:
Interventional
Actual Enrollment
:
34 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Randomized double-blind placebo-controlledRandomized double-blind placebo-controlled
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo-controlled Study of the Safety, Pharmacodynamics, Efficacy, and Pharmacokinetics of TIMP-GLIA in Subjects With Well-controlled Celiac Disease Undergoing Oral Gluten Challenge
Actual Study Start Date
:
Nov 11, 2018
Actual Primary Completion Date
:
Jun 24, 2019
Actual Study Completion Date
:
Jul 22, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TIMP-GLIA 8 mg/kg up to a maximum of 650 mg administered intravenously on days 1 and 8. |
Drug: TIMP-GLIA
8 mg/kg up to a maximum of 650 mg administered intravenously on days 1 and 8.
Other Names:
|
| Placebo Comparator: Placebo Normal saline administered intravenously on days 1 and 8. |
Drug: Placebo
Administered intravenously on days 1 and 8.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Interferon-Gamma Spot Forming Units (IFN-gamma SFUs) in a Gliadin-specific Enzyme-linked Immunospot (ELISpot) at Day 20 [Baseline (Day 15/Day 1), Day 20]
The spots formed by interferon-gamma-secreting T-cells were counted with an automated ELISPOT analyzer. The average spot-forming units (SFU) per antigen was calculated. A response was considered positive when the average SFU in wells with a given peptide was at least twice that of the average SFU in the no-peptide control wells. Baseline (Day 15/Day 1) was defined as Day 15 (or Day 1 if enough blood was not available on Day 15). Peripheral blood mononuclear cell is PBMC.
Secondary Outcome Measures
- Change From Baseline in Gliadin-specific T Cell Proliferation by Enzyme-linked Immunosorbent Assay (ELISA) at Day 20 [Baseline (Day 15/Day 1), Day 20]
Gliadin-specific T cell proliferation was determined by ELISA test. Baseline (Day 15/Day 1) was defined as Day 15 (or Day 1 if enough blood was not available on Day 15).
- Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 [Baseline (Day 15/Day 1), Day 20]
Gliadin-specific T Cell cytokine secretion was determined by ELISA test. Gliadin-specific cytokine included interferon gamma (IFN-γ), interleukin (IL) 1-beta (1-β), IL-10, IL-12, IL-13, IL-2, IL-4, IL-6, IL-8, tumor necrosis factor alpha (TNF-α). Baseline (Day 15/Day 1) was defined as Day 15 (or Day 1 if enough blood was not available on Day 15). A negative change from baseline value was reported when the observed sample response was less than the observed background response.
- Change From Baseline in Gut-Homing CD4, CD8 and Gamma Delta T-cells by Mass Cytometry (CyTOF) at Day 20 [Baseline (Day 15/Day 1), Day 20]
Change from baseline value for Gut-Homing cells like CD4, CD8 and Gamma Delta T-cells were reported. Baseline (Day 15/Day 1) was defined as Day 15 (or Day 1 if enough blood was not available on Day 15). Phenotype (unique cell population) for CD8 cell is EM CD8 > aE+b7hi > aE+b7hiCD38+, for CD4 is EM Th > a4+b7hi > a4+b7hiCD38+ and for Gamma Delta T-cells is TCRgd T cells > aE+b7hi > aE+b7hiCD38+ in this outcome measure.
- Change From Baseline in Ratio of Villus Height to Crypt Depth (Vh:Cd) at Day 29 [Baseline (Screening), Day 29]
Attenuation of the effects of gluten exposure was assessed by measuring the change from baseline in villous height (Vh) to crypt depth (Cd) ratio after 29 days of gluten challenge. Villi were the small finger like projections that line the small intestine and promote nutrient absorption and are often shortened in participants with CD. Crypts are grooves between the villi that are often elongated in participants with CD. A decreased Vh:Cd ratio indicates worsening disease. Baseline was defined as the last sample collected prior to the first dose of study medication (Screening Period) on Day 1.
- Percentage of Participants With Greater Than or Equal to (>=) 0.4 Decrease in Vh:Cd at Day 29 [Day 29]
Villi were the small finger like projections that line the small intestine and promote nutrient absorption and are often shortened in participants with CD. Crypts are grooves between the villi that are often elongated in participants with CD. A decreased Vh:Cd ratio indicates worsening disease.
- Change From Baseline in Number of Intestinal Intraepithelial Lymphocytes (IELs) at Day 29 [Baseline (Screening), Day 29]
IELs were white blood cells interspersed between epithelial cells of the small and large intestine where they function to preserve the integrity of the mucosal barrier by protecting the epithelium against pathogen or immune-induced pathology. Increased intraepithelial lymphocytes was associated with celiac disease. Baseline was defined as the last sample collected prior to the first dose of study medication (Screening Period) on Day 1.
- Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment [Days 15, 20, 29 and 35]
The CSI were clinically oriented, easily administered, questionnaires with 16 items. The modified CSI (6-items) was derived from a subset of questions from the CSI questionnaire, including the diarrhea, nausea, rumbling in stomach, stomach felt bloated, diarrhea and low energy level abdominal pain domains (a total of 6 questions), which were each assessed on a scale of 1 to 5- none of the time, a little of the time, some of the time, most of the time and all of the time respectively. Higher CSI scores correlate with more severe CD symptoms. It is to be used to assess symptoms before, during, and after the oral gluten challenge. Here D refers to Day.
- Plasma Concentrations of TIMP-GLIA [Day 8: 0 hours (pre-infusion), end of infusion, and at 2 hours post-infusion]
- Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) [From the first dose of study drug up to Day 35]
- Number of Participants With Clinically Significant Change From Baseline in Vital Signs [From the first dose of study drug up to Day 35]
- Number of Participants With Clinically Significant Change From Baseline in Hematology or Serum Chemistry Laboratory Values [From the first dose of study drug up to Day 35]
- Change From Baseline in Deamidated Gliadin Peptide Immunoglobulin G (DGP-IgG) Antibodies at Days 8, 15, 20, 29, and 35 [Baseline (Screening), Days 8, 15, 20, 29, and 35]
Baseline was defined as the last sample collected prior to the first dose of study medication (Screening Period) on Day 1.
- Change From Baseline in Serum Complement Levels of C3a and SC5B-9 at Days 2, 8, 9, and 15 [Baseline (Day 1), Days 2, 8, 9, and 15]
Baseline was defined as the pre-dose value on Day 1.
- Change From Baseline in Serum Complement Levels of C5a at Days 2, 8, 9, and 15 [Baseline (Day 1) , Days 2, 8, 9, and 15]
Baseline was defined as the pre-dose value on Day 1.
- Change From Baseline in Serum Complement Levels of C1q Binding at Days 15, 20, 29, and 35 [Baseline (Day 1), Days 15, 20, 29, and 35]
Baseline was defined as the pre-dose value on Day 1.
- 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 [Baseline (Day 1), Days 2, 8, 9, and 15]
Baseline was defined as Day 1 pre-dose. A negative change from baseline value was reported when the observed sample response was less than the observed background response.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 < 3 mg/dL, negative or weak positive DGP- IgG titer.
-
Vh:Cd ≥ 1.5 on screening biopsy.
Key Exclusion Criteria:
-
Positive for only HLA-DQ8.
-
History of clinically confirmed immunoglobulin E (IgE)-mediated reaction and/or anaphylaxis to wheat (i.e., "wheat allergy"), barley or rye.
-
Uncontrolled CD and/or active signs/symptoms of CD, in the opinion of the investigator.
-
Untreated or active gastrointestinal disease such as peptic ulcer disease, esophagitis (Los Angeles Classification ≥ Grade C), irritable bowel syndrome, inflammatory bowel disease, or microscopic colitis.
-
Immunocompromised individuals, including those receiving immunosuppressive doses of corticosteroids (more than 20 mg of prednisone given daily or on alternative days for 2 weeks or more within 6 months prior Dose 1, any dose of corticosteroids within 30 days of Day 1, or high dose inhaled corticosteroids [> 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Jacksonville Center for Clinical Research | Jacksonville | Florida | United States | 32216 |
| 2 | Advanced Clinical Research | Meridian | Idaho | United States | 83642 |
| 3 | Indianapolis Gastroenterology Research Foundation | Indianapolis | Indiana | United States | 46237 |
| 4 | Beth Isreal Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
| 5 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 6 | Prism Clinical Research | Saint Paul | Minnesota | United States | 55114 |
| 7 | Rapid Medical Research | Beachwood | Ohio | United States | 44122 |
| 8 | Advanced Clinical Research | West Jordan | Utah | United States | 84088 |
Sponsors and Collaborators
- Takeda
- COUR Pharmaceuticals Development Company, Inc.
Investigators
- Study Director: Medical Director Clinical Science, Takeda
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT03738475
Other Study ID Numbers:
- TGLIA-5.002
First Posted:
Nov 13, 2018
Last Update Posted:
Aug 12, 2020
Last Verified:
Jul 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants took part in the study at 6 investigative sites in the United States from 11 November 2018 to 22 July 2019. |
|---|---|
| Pre-assignment Detail | Participants diagnosed with celiac disease (CD) were enrolled in a 1:1 ratio in one of two treatment groups: Tolerogenic Immune Modifying Particles - Gliadin (TIMP-GLIA) or Placebo. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo |
|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 milligram per kilogram (mg/kg), infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Period Title: Overall Study | ||
| STARTED | 16 | 18 |
| COMPLETED | 15 | 18 |
| NOT COMPLETED | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. | Total of all reporting groups |
| Overall Participants | 16 | 18 | 34 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
44.6
(13.47)
|
42.2
(16.71)
|
43.3
(15.09)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
13
81.3%
|
15
83.3%
|
28
82.4%
|
| Male |
3
18.8%
|
3
16.7%
|
6
17.6%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
1
6.3%
|
0
0%
|
1
2.9%
|
| Not Hispanic or Latino |
15
93.8%
|
18
100%
|
33
97.1%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
16
100%
|
18
100%
|
34
100%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | |||
| United States |
16
100%
|
18
100%
|
34
100%
|
| Body Mass Index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kilogram per square meter (kg/m^2)] |
28.213
(4.8479)
|
27.100
(4.8214)
|
27.624
(4.7933)
|
| Disease Duration (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
9.30
|
8.45
|
8.95
|
| Gluten Free Diet Duration (months) [Median (Full Range) ] | |||
| Median (Full Range) [months] |
111.10
|
113.45
|
111.10
|
Outcome Measures
| Title | Change From Baseline in Interferon-Gamma Spot Forming Units (IFN-gamma SFUs) in a Gliadin-specific Enzyme-linked Immunospot (ELISpot) at Day 20 |
|---|---|
| Description | The spots formed by interferon-gamma-secreting T-cells were counted with an automated ELISPOT analyzer. The average spot-forming units (SFU) per antigen was calculated. A response was considered positive when the average SFU in wells with a given peptide was at least twice that of the average SFU in the no-peptide control wells. Baseline (Day 15/Day 1) was defined as Day 15 (or Day 1 if enough blood was not available on Day 15). Peripheral blood mononuclear cell is PBMC. |
| Time Frame | Baseline (Day 15/Day 1), Day 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacodynamic population included all randomized participants who received two doses of study medication, completed at least the first 3 days of the gluten challenge (12 grams per day [g/day] for 3 days), and had pharmacodynamic results on Study Days 1, 15, and 20. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo |
|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Measure Participants | 13 | 16 |
| Baseline (Day 15/Day 1) |
3.08
(5.263)
|
1.98
(3.184)
|
| Change at Day 20 |
2.01
(6.958)
|
17.57
(25.283)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TIMP-GLIA 8 mg/kg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0056 |
| Comments | Based on Wilcoxon Rank Sum test for the change from baseline between treatment groups. | |
| Method | Wilcoxon Rank Sum test | |
| Comments | ||
| Title | Change From Baseline in Gliadin-specific T Cell Proliferation by Enzyme-linked Immunosorbent Assay (ELISA) at Day 20 |
|---|---|
| Description | Gliadin-specific T cell proliferation was determined by ELISA test. Baseline (Day 15/Day 1) was defined as Day 15 (or Day 1 if enough blood was not available on Day 15). |
| Time Frame | Baseline (Day 15/Day 1), Day 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacodynamic population included all randomized participants who received two doses of study medication, completed at least the first 3 days of the gluten challenge (12 g/day for 3 days), and had pharmacodynamic results on Study Days 1, 15, and 20. Participants evaluable for this measure at given time point were included for the assessment. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo |
|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Measure Participants | 13 | 16 |
| Baseline (Day 15/Day 1) |
0.87
(0.275)
|
1.00
(0.178)
|
| Change at Day 20 |
0.05
(0.284)
|
0.00
(0.180)
|
| Title | Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at Day 20 |
|---|---|
| Description | Gliadin-specific T Cell cytokine secretion was determined by ELISA test. Gliadin-specific cytokine included interferon gamma (IFN-γ), interleukin (IL) 1-beta (1-β), IL-10, IL-12, IL-13, IL-2, IL-4, IL-6, IL-8, tumor necrosis factor alpha (TNF-α). Baseline (Day 15/Day 1) was defined as Day 15 (or Day 1 if enough blood was not available on Day 15). A negative change from baseline value was reported when the observed sample response was less than the observed background response. |
| Time Frame | Baseline (Day 15/Day 1), Day 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacodynamic population included all randomized participants who received two doses of study medication, completed at least the first 3 days of the gluten challenge (12 g/day for 3 days), and had pharmacodynamic results on Study Days 1, 15, and 20. Participants evaluable for this measure at given time point were included for the assessment. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo |
|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Measure Participants | 13 | 16 |
| Baseline (Day 15/Day 1): IFN-γ |
1.44
(2.727)
|
1.70
(4.251)
|
| Change at Day 20: IFN-γ |
-0.43
(2.044)
|
-0.01
(2.149)
|
| Baseline (Day 15/Day 1): IL1-β |
1.24
(1.507)
|
2.68
(4.548)
|
| Change at Day 20: IL1-β |
0.00
(1.456)
|
-0.12
(5.946)
|
| Baseline (Day 15/Day 1): IL-10 |
0.42
(0.688)
|
0.80
(1.135)
|
| Change at Day 20 :IL-10 |
0.53
(0.754)
|
-0.21
(1.302)
|
| Baseline (Day 15/Day 1): IL-12 |
0.23
(0.727)
|
-0.03
(0.755)
|
| Change at Day 20: IL-12 |
-0.01
(0.616)
|
0.13
(0.548)
|
| Baseline (Day 15/Day 1): IL-13 |
2.23
(2.831)
|
0.94
(3.504)
|
| Change at Day 20: IL-13 |
-2.06
(5.700)
|
0.36
(1.655)
|
| Baseline (Day 15/Day 1): IL-2 |
1.00
(1.117)
|
1.29
(1.510)
|
| Change at Day 20: IL-2 |
0.27
(1.180)
|
0.20
(0.932)
|
| Baseline (Day 15/Day 1): IL-4 |
0.12
(0.180)
|
0.19
(0.388)
|
| Change at Day 20: IL-4 |
-0.07
(0.227)
|
-0.09
(0.434)
|
| Baseline (Day 15/Day 1): IL-6 |
-0.59
(18.704)
|
32.06
(123.405)
|
| Change at Day 20: IL-6 |
12.76
(29.303)
|
-16.88
(131.535)
|
| Baseline (Day 15/Day 1): IL-8 |
0.03
(0.091)
|
0.00
(0.007)
|
| Change at Day 20: IL-8 |
-0.03
(0.091)
|
0.00
(0.007)
|
| Baseline (Day 15/Day 1): TNF-α |
2.25
(2.763)
|
11.75
(27.434)
|
| Change at Day 20: TNF-α |
3.20
(3.099)
|
-1.95
(33.181)
|
| Title | Change From Baseline in Gut-Homing CD4, CD8 and Gamma Delta T-cells by Mass Cytometry (CyTOF) at Day 20 |
|---|---|
| Description | Change from baseline value for Gut-Homing cells like CD4, CD8 and Gamma Delta T-cells were reported. Baseline (Day 15/Day 1) was defined as Day 15 (or Day 1 if enough blood was not available on Day 15). Phenotype (unique cell population) for CD8 cell is EM CD8 > aE+b7hi > aE+b7hiCD38+, for CD4 is EM Th > a4+b7hi > a4+b7hiCD38+ and for Gamma Delta T-cells is TCRgd T cells > aE+b7hi > aE+b7hiCD38+ in this outcome measure. |
| Time Frame | Baseline (Day 15/Day 1), Day 20 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacodynamic population included all randomized participants who received two doses of study medication, completed at least the first 3 days of the gluten challenge (12 g/day for 3 days), and had pharmacodynamic results on Study Days 1, 15, and 20. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo |
|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Measure Participants | 13 | 16 |
| Baseline (Day 15/Day 1): CD8 |
0.21
(0.216)
|
0.18
(0.285)
|
| Change at Day 20: CD8 |
0.69
(0.979)
|
3.64
(3.685)
|
| Baseline (Day 15/Day 1): CD4 |
0.19
(0.210)
|
0.16
(0.189)
|
| Change at Day 20: CD4 |
0.26
(0.549)
|
1.05
(1.223)
|
| Baseline (Day 15/Day 1): Gamma Delta T-cells |
0.20
(0.186)
|
0.13
(0.318)
|
| Change at Day 20: Gamma Delta T-cells |
0.15
(0.378)
|
1.59
(2.598)
|
| Title | Change From Baseline in Ratio of Villus Height to Crypt Depth (Vh:Cd) at Day 29 |
|---|---|
| Description | Attenuation of the effects of gluten exposure was assessed by measuring the change from baseline in villous height (Vh) to crypt depth (Cd) ratio after 29 days of gluten challenge. Villi were the small finger like projections that line the small intestine and promote nutrient absorption and are often shortened in participants with CD. Crypts are grooves between the villi that are often elongated in participants with CD. A decreased Vh:Cd ratio indicates worsening disease. Baseline was defined as the last sample collected prior to the first dose of study medication (Screening Period) on Day 1. |
| Time Frame | Baseline (Screening), Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The histology population included all randomized participants who received two doses of study medication, completed the gluten challenge per protocol, and had both a baseline and Day 29 biopsy. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo |
|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Measure Participants | 13 | 15 |
| Baseline (Screening): Vh:Cd |
2.82
(0.306)
|
3.01
(0.451)
|
| Change at Day 29: Vh:Cd: |
-0.18
(0.381)
|
-0.63
(0.657)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TIMP-GLIA 8 mg/kg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0799 |
| Comments | Based on Wilcoxon Rank Sum test for the change from baseline between treatment groups. | |
| Method | Wilcoxon Rank Sum test | |
| Comments | ||
| Title | Percentage of Participants With Greater Than or Equal to (>=) 0.4 Decrease in Vh:Cd at Day 29 |
|---|---|
| Description | Villi were the small finger like projections that line the small intestine and promote nutrient absorption and are often shortened in participants with CD. Crypts are grooves between the villi that are often elongated in participants with CD. A decreased Vh:Cd ratio indicates worsening disease. |
| Time Frame | Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The histology population included all randomized participants who received two doses of study medication, completed the gluten challenge per protocol, and had both a baseline and Day 29 biopsy. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo |
|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Measure Participants | 13 | 15 |
| Number [percentage of participants] |
23.1
144.4%
|
53.3
296.1%
|
| Title | Change From Baseline in Number of Intestinal Intraepithelial Lymphocytes (IELs) at Day 29 |
|---|---|
| Description | IELs were white blood cells interspersed between epithelial cells of the small and large intestine where they function to preserve the integrity of the mucosal barrier by protecting the epithelium against pathogen or immune-induced pathology. Increased intraepithelial lymphocytes was associated with celiac disease. Baseline was defined as the last sample collected prior to the first dose of study medication (Screening Period) on Day 1. |
| Time Frame | Baseline (Screening), Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The histology population included all randomized participants who received two doses of study medication, completed the gluten challenge per protocol, and had both a baseline and Day 29 biopsy. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo |
|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Measure Participants | 13 | 15 |
| Baseline (Screening): IELs |
39.62
(18.842)
|
34.53
(12.389)
|
| Change at Day 29: IELs |
28.62
(19.241)
|
35.00
(18.756)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TIMP-GLIA 8 mg/kg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2890 |
| Comments | Based on Wilcoxon Rank Sum test for the change from baseline between treatment groups. | |
| Method | Wilcoxon Rank Sum test | |
| Comments | ||
| Title | Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment |
|---|---|
| Description | The CSI were clinically oriented, easily administered, questionnaires with 16 items. The modified CSI (6-items) was derived from a subset of questions from the CSI questionnaire, including the diarrhea, nausea, rumbling in stomach, stomach felt bloated, diarrhea and low energy level abdominal pain domains (a total of 6 questions), which were each assessed on a scale of 1 to 5- none of the time, a little of the time, some of the time, most of the time and all of the time respectively. Higher CSI scores correlate with more severe CD symptoms. It is to be used to assess symptoms before, during, and after the oral gluten challenge. Here D refers to Day. |
| Time Frame | Days 15, 20, 29 and 35 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all randomized participants who received at least one dose of study medication. Here, "number analyzed" signifies the participants who were evaluable for this outcome measure for given time points. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo |
|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Measure Participants | 16 | 18 |
| D 15, Pain/discomfort in abdomen/stomach: None |
11
68.8%
|
13
72.2%
|
| D 15, Pain/discomfort in abdomen/stomach: A little |
3
18.8%
|
4
22.2%
|
| D 15, Pain/discomfort in abdomen/stomach: Some |
2
12.5%
|
1
5.6%
|
| D 15, Pain/discomfort in abdomen/stomach: Most |
0
0%
|
0
0%
|
| D 15, Pain/discomfort in abdomen/stomach: All time |
0
0%
|
0
0%
|
| D 15, Nausea: None |
12
75%
|
15
83.3%
|
| D 15, Nausea: A little |
2
12.5%
|
2
11.1%
|
| D 15, Nausea: Some |
1
6.3%
|
1
5.6%
|
| D 15, Nausea: Most |
1
6.3%
|
0
0%
|
| D 15, Nausea: All time |
0
0%
|
0
0%
|
| D 15, Rumbling in stomach: None |
12
75%
|
11
61.1%
|
| D 15, Rumbling in stomach: A little |
2
12.5%
|
5
27.8%
|
| D 15, Rumbling in stomach: Some |
2
12.5%
|
2
11.1%
|
| D 15, Rumbling in stomach: Most |
0
0%
|
0
0%
|
| D 15, Rumbling in stomach: All time |
0
0%
|
0
0%
|
| D 15, Stomach felt bloated: None |
11
68.8%
|
10
55.6%
|
| D 15, Stomach felt bloated: A little |
4
25%
|
7
38.9%
|
| D 15, Stomach felt bloated: Some |
1
6.3%
|
0
0%
|
| D 15, Stomach felt bloated: Most |
0
0%
|
1
5.6%
|
| D 15, Stomach felt bloated: All time |
0
0%
|
0
0%
|
| D 15, Diarrhea: None |
14
87.5%
|
15
83.3%
|
| D 15, Diarrhea: A little |
2
12.5%
|
3
16.7%
|
| D 15, Diarrhea: Some |
0
0%
|
0
0%
|
| D 15, Diarrhea: Most |
0
0%
|
0
0%
|
| D 15, Diarrhea: All time |
0
0%
|
0
0%
|
| D 15, Low energy level: None |
6
37.5%
|
11
61.1%
|
| D 15, Low energy level: A little |
5
31.3%
|
5
27.8%
|
| D 15, Low energy level: Some |
3
18.8%
|
1
5.6%
|
| D 15, Low energy level: Most |
2
12.5%
|
1
5.6%
|
| D 15, Low energy level: All time |
0
0%
|
0
0%
|
| D 20, Pain/discomfort in abdomen/stomach: None |
5
31.3%
|
8
44.4%
|
| D 20, Pain/discomfort in abdomen/stomach: A little |
4
25%
|
3
16.7%
|
| D 20, Pain/discomfort in abdomen/stomach: Some |
2
12.5%
|
4
22.2%
|
| D 20, Pain/discomfort in abdomen/stomach: Most |
3
18.8%
|
2
11.1%
|
| D 20, Pain/discomfort in abdomen/stomach: All time |
0
0%
|
1
5.6%
|
| D 20, Nausea: None |
4
25%
|
5
27.8%
|
| D 20, Nausea: A little |
5
31.3%
|
7
38.9%
|
| D 20, Nausea: Some |
3
18.8%
|
3
16.7%
|
| D 20, Nausea: Most |
1
6.3%
|
2
11.1%
|
| D 20, Nausea: All time |
1
6.3%
|
1
5.6%
|
| D 20, Rumbling in stomach: None |
6
37.5%
|
6
33.3%
|
| D 20, Rumbling in stomach: A little |
2
12.5%
|
6
33.3%
|
| D 20, Rumbling in stomach: Some |
4
25%
|
3
16.7%
|
| D 20, Rumbling in stomach: Most |
1
6.3%
|
2
11.1%
|
| D 20, Rumbling in stomach: All time |
1
6.3%
|
1
5.6%
|
| D 20, Stomach felt bloated: None |
7
43.8%
|
4
22.2%
|
| D 20, Stomach felt bloated: A little |
2
12.5%
|
8
44.4%
|
| D 20, Stomach felt bloated: Some |
1
6.3%
|
3
16.7%
|
| D 20, Stomach felt bloated: Most |
2
12.5%
|
1
5.6%
|
| D 20, Stomach felt bloated: All time |
2
12.5%
|
2
11.1%
|
| D 20, Diarrhea: None |
8
50%
|
11
61.1%
|
| D 20, Diarrhea: A little |
2
12.5%
|
4
22.2%
|
| D 20, Diarrhea: Some |
3
18.8%
|
3
16.7%
|
| D 20, Diarrhea: Most |
1
6.3%
|
0
0%
|
| D 20, Diarrhea: All time |
0
0%
|
0
0%
|
| D 20, Low energy level: None |
3
18.8%
|
6
33.3%
|
| D 20, Low energy level: A little |
5
31.3%
|
6
33.3%
|
| D 20, Low energy level: Some |
0
0%
|
2
11.1%
|
| D 20, Low energy level: Most |
4
25%
|
2
11.1%
|
| D 20, Low energy level: All time |
2
12.5%
|
2
11.1%
|
| D 29, Pain/discomfort in abdomen/stomach: None |
6
37.5%
|
10
55.6%
|
| D 29, Pain/discomfort in abdomen/stomach: A little |
2
12.5%
|
5
27.8%
|
| D 29, Pain/discomfort in abdomen/stomach: Some |
4
25%
|
2
11.1%
|
| D 29, Pain/discomfort in abdomen/stomach: Most |
1
6.3%
|
0
0%
|
| D 29, Pain/discomfort in abdomen/stomach: All time |
0
0%
|
1
5.6%
|
| D 29, Nausea: None |
8
50%
|
9
50%
|
| D 29, Nausea: A little |
3
18.8%
|
5
27.8%
|
| D 29, Nausea: Some |
1
6.3%
|
1
5.6%
|
| D 29, Nausea: Most |
1
6.3%
|
2
11.1%
|
| D 29, Nausea: All time |
0
0%
|
1
5.6%
|
| D 29, Rumbling in stomach: None |
7
43.8%
|
9
50%
|
| D 29, Rumbling in stomach: A little |
1
6.3%
|
5
27.8%
|
| D 29, Rumbling in stomach: Some |
3
18.8%
|
2
11.1%
|
| D 29, Rumbling in stomach: Most |
2
12.5%
|
1
5.6%
|
| D 29, Rumbling in stomach: All time |
0
0%
|
1
5.6%
|
| D 29, Stomach felt bloated: None |
7
43.8%
|
8
44.4%
|
| D 29, Stomach felt bloated: A little |
1
6.3%
|
6
33.3%
|
| D 29, Stomach felt bloated: Some |
2
12.5%
|
1
5.6%
|
| D 29, Stomach felt bloated: Most |
2
12.5%
|
2
11.1%
|
| D 29, Stomach felt bloated: All time |
1
6.3%
|
1
5.6%
|
| D 29, Diarrhea: None |
10
62.5%
|
13
72.2%
|
| D 29, Diarrhea: A little |
1
6.3%
|
3
16.7%
|
| D 29, Diarrhea: Some |
2
12.5%
|
1
5.6%
|
| D 29, Diarrhea: Most |
0
0%
|
0
0%
|
| D 29, Diarrhea: All time |
0
0%
|
1
5.6%
|
| D 29, Low energy level: None |
4
25%
|
8
44.4%
|
| D 29, Low energy level: A little |
3
18.8%
|
6
33.3%
|
| D 29, Low energy level: Some |
2
12.5%
|
3
16.7%
|
| D 29, Low energy level: Most |
3
18.8%
|
0
0%
|
| D 29, Low energy level: All time |
1
6.3%
|
1
5.6%
|
| D 35, Pain/discomfort in abdomen/stomach: None |
8
50%
|
15
83.3%
|
| D 35, Pain/discomfort in abdomen/stomach: A little |
4
25%
|
2
11.1%
|
| D 35, Pain/discomfort in abdomen/stomach: Some |
1
6.3%
|
1
5.6%
|
| D 35, Pain/discomfort in abdomen/stomach: Most |
0
0%
|
0
0%
|
| D 35, Pain/discomfort in abdomen/stomach: All time |
0
0%
|
0
0%
|
| D 35, Nausea: None |
9
56.3%
|
16
88.9%
|
| D 35, Nausea: A little |
2
12.5%
|
2
11.1%
|
| D 35, Nausea: Some |
2
12.5%
|
0
0%
|
| D 35, Nausea: Most |
0
0%
|
0
0%
|
| D 35, Nausea: All time |
0
0%
|
0
0%
|
| D 35, Rumbling in stomach: None |
10
62.5%
|
11
61.1%
|
| D 35, Rumbling in stomach: A little |
1
6.3%
|
7
38.9%
|
| D 35, Rumbling in stomach: Some |
2
12.5%
|
0
0%
|
| D 35, Rumbling in stomach: Most |
0
0%
|
0
0%
|
| D 35, Rumbling in stomach: All time |
0
0%
|
0
0%
|
| D 35, Stomach felt bloated: None |
8
50%
|
10
55.6%
|
| D 35, Stomach felt bloated: A little |
3
18.8%
|
6
33.3%
|
| D 35, Stomach felt bloated: Some |
2
12.5%
|
2
11.1%
|
| D 35, Stomach felt bloated: Most |
0
0%
|
0
0%
|
| D 35, Stomach felt bloated: All time |
0
0%
|
0
0%
|
| D 35, Diarrhea: None |
11
68.8%
|
14
77.8%
|
| D 35, Diarrhea: A little |
2
12.5%
|
3
16.7%
|
| D 35, Diarrhea: Some |
0
0%
|
0
0%
|
| D 35, Diarrhea: Most |
0
0%
|
1
5.6%
|
| D 35, Diarrhea: All time |
0
0%
|
0
0%
|
| D 35, Low energy level: None |
7
43.8%
|
14
77.8%
|
| D 35, Low energy level: A little |
1
6.3%
|
2
11.1%
|
| D 35, Low energy level: Some |
4
25%
|
0
0%
|
| D 35, Low energy level: Most |
1
6.3%
|
2
11.1%
|
| D 35, Low energy level: All time |
0
0%
|
0
0%
|
| Title | Plasma Concentrations of TIMP-GLIA |
|---|---|
| Description | |
| Time Frame | Day 8: 0 hours (pre-infusion), end of infusion, and at 2 hours post-infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacokinetic population included all randomized participants who received two doses of study medication and had at least one reported concentration. The pharmacokinetic population where data at specified time points were available. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg |
|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. |
| Measure Participants | 16 |
| 0 hours (pre-infusion) |
13.06
(52.250)
|
| End of Infusion |
684.54
(319.069)
|
| 2 hours post infusion |
383.46
(153.225)
|
| Title | Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) |
|---|---|
| Description | |
| Time Frame | From the first dose of study drug up to Day 35 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all randomized participants who received at least one dose of study medication. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo |
|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Measure Participants | 16 | 18 |
| TEAE |
16
100%
|
18
100%
|
| SAE |
0
0%
|
0
0%
|
| Title | Number of Participants With Clinically Significant Change From Baseline in Vital Signs |
|---|---|
| Description | |
| Time Frame | From the first dose of study drug up to Day 35 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all randomized participants who received at least one dose of study medication. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo |
|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Measure Participants | 16 | 18 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
| Title | Number of Participants With Clinically Significant Change From Baseline in Hematology or Serum Chemistry Laboratory Values |
|---|---|
| Description | |
| Time Frame | From the first dose of study drug up to Day 35 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all randomized participants who received at least one dose of study medication. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo |
|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Measure Participants | 16 | 18 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
| Title | Change From Baseline in Deamidated Gliadin Peptide Immunoglobulin G (DGP-IgG) Antibodies at Days 8, 15, 20, 29, and 35 |
|---|---|
| Description | Baseline was defined as the last sample collected prior to the first dose of study medication (Screening Period) on Day 1. |
| Time Frame | Baseline (Screening), Days 8, 15, 20, 29, and 35 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all randomized participants who received at least one dose of study medication. Participants evaluable for this measure at given time point were included for the assessment. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo |
|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Measure Participants | 16 | 18 |
| Baseline (Screening) |
7.9
(11.53)
|
5.9
(3.48)
|
| Change at Day 8 |
4.3
(7.43)
|
-0.6
(1.58)
|
| Change at Day 15 |
27.8
(28.92)
|
0.3
(1.67)
|
| Change at Day 20 |
28.6
(29.63)
|
-0.1
(1.76)
|
| Change at Day 29 |
28.4
(31.27)
|
8.9
(13.23)
|
| Change at Day 35 |
28.4
(29.68)
|
20.7
(27.04)
|
| Title | Change From Baseline in Serum Complement Levels of C3a and SC5B-9 at Days 2, 8, 9, and 15 |
|---|---|
| Description | Baseline was defined as the pre-dose value on Day 1. |
| Time Frame | Baseline (Day 1), Days 2, 8, 9, and 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all randomized participants who received at least one dose of study medication. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo |
|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Measure Participants | 16 | 18 |
| Baseline (Day 1): C3a |
1024.0
(430.15)
|
1069.9
(435.78)
|
| Change at Day 2: C3a |
-144.6
(452.51)
|
112.3
(1086.95)
|
| Change at Day 8: C3a |
244.7
(449.20)
|
-115.3
(385.44)
|
| Change at Day 9: C3a |
-63.0
(227.28)
|
-71.2
(441.80)
|
| Change at Day 15: C3a |
-165.2
(308.01)
|
54.8
(603.56)
|
| Baseline (Day 1): SC5B-9 |
130.5
(44.69)
|
114.7
(40.68)
|
| Change at Day 2: SC5B-9 |
-8.7
(25.83)
|
-4.5
(20.18)
|
| Change at Day 8: SC5B-9 |
866.5
(924.08)
|
-4.6
(28.72)
|
| Change at Day 9: SC5B-9 |
40.5
(137.83)
|
-4.8
(37.18)
|
| Change at Day 15: SC5B-9 |
5.5
(57.06)
|
18.4
(53.46)
|
| Title | Change From Baseline in Serum Complement Levels of C5a at Days 2, 8, 9, and 15 |
|---|---|
| Description | Baseline was defined as the pre-dose value on Day 1. |
| Time Frame | Baseline (Day 1) , Days 2, 8, 9, and 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all randomized participants who received at least one dose of study medication. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo |
|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Measure Participants | 16 | 18 |
| Baseline (Day 1) |
9.290
(6.5091)
|
7.267
(3.2526)
|
| Change at Day 2 |
0.763
(1.0587)
|
-0.067
(0.6776)
|
| Change at Day 8 |
8.373
(8.0077)
|
0.082
(0.7604)
|
| Change at Day 9 |
0.926
(1.3873)
|
0.347
(1.0356)
|
| Change at Day 15 |
0.319
(1.7868)
|
0.241
(0.9151)
|
| Title | Change From Baseline in Serum Complement Levels of C1q Binding at Days 15, 20, 29, and 35 |
|---|---|
| Description | Baseline was defined as the pre-dose value on Day 1. |
| Time Frame | Baseline (Day 1), Days 15, 20, 29, and 35 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all randomized participants who received at least one dose of study medication. Participants who were evaluable for this measure at given time point were included for the assessment. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo |
|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Measure Participants | 16 | 18 |
| Baseline (Day 1) |
3.65
(2.026)
|
4.53
(1.962)
|
| Change at Day 15 |
0.64
(1.249)
|
0.21
(1.498)
|
| Change at Day 20 |
0.88
(1.315)
|
-0.15
(1.274)
|
| Change at Day 29 |
0.10
(1.901)
|
0.18
(2.073)
|
| Change at Day 35 |
0.49
(1.310)
|
0.09
(2.116)
|
| Title | 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 |
|---|---|
| Description | Baseline was defined as Day 1 pre-dose. A negative change from baseline value was reported when the observed sample response was less than the observed background response. |
| Time Frame | Baseline (Day 1), Days 2, 8, 9, and 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population included all randomized participants who received at least one dose of study medication. |
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo |
|---|---|---|
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Measure Participants | 16 | 18 |
| Baseline (Day 1): IFN-γ |
7.375
(9.5787)
|
4.592
(1.9801)
|
| Change at Day 2: IFN-γ |
9.871
(19.3167)
|
-0.179
(0.8403)
|
| Change at Day 8: IFN-γ |
-2.374
(10.3311)
|
5.245
(15.7119)
|
| Change at Day 9: IFN-γ |
1.663
(14.7044)
|
3.709
(12.0744)
|
| Change at Day 15: IFN-γ |
0.539
(12.8988)
|
0.871
(2.4732)
|
| Baseline (Day 1): IL1-β |
0.600
(0.0000)
|
0.600
(0.0000)
|
| Change at Day 2: IL1-β |
0.000
(0.0000)
|
0.0000
(0.0000)
|
| Change at Day 8: IL1-β |
0.000
(0.000)
|
0.0000
(0.0000)
|
| Change at Day 9: IL1-β |
0.000
(0.000)
|
0.0000
(0.0000)
|
| Change at Day 15: IL1-β |
0.000
(0.000)
|
0.0000
(0.0000)
|
| Baseline (Day 1): IL-2 |
0.731
(0.0450)
|
0.824
(0.4431)
|
| Change at Day 2: IL-2 |
0.004
(0.0175)
|
0.001
(0.0047)
|
| Change at Day 8: IL-2 |
0.008
(0.0325)
|
-0.021
(0.0872)
|
| Change at Day 9: IL-2 |
0.006
(0.0250)
|
-0.022
(0.0943)
|
| Change at Day 15: IL-2 |
0.006
(0.0250)
|
-0.023
(0.0990)
|
| Baseline (Day 1): IL-4 |
0.380
(0.0000)
|
0.380
(0.0000)
|
| Change at Day 2: IL-4 |
0.000
(0.000)
|
0.0000
(0.0000)
|
| Change at Day 8: IL-4 |
0.000
(0.000)
|
0.0000
(0.0000)
|
| Change at Day 9: IL-4 |
0.000
(0.000)
|
0.0000
(0.0000)
|
| Change at Day 15: IL-4 |
0.000
(0.000)
|
0.0000
(0.0000)
|
| Baseline (Day 1): IL-6 |
1.067
(0.3473)
|
1.005
(0.1621)
|
| Change at Day 2: IL-6 |
-0.009
(0.0924)
|
0.069
(0.2733)
|
| Change at Day 8: IL-6 |
0.024
(0.3507)
|
0.169
(0.6991)
|
| Change at Day 9: IL-6 |
0.159
(0.4817)
|
0.051
(0.2330)
|
| Change at Day 15: IL-6 |
-0.059
(0.3768)
|
-0.008
(0.1400)
|
| Baseline (Day 1): IL-8 |
12.602
(5.7067)
|
11.497
(3.9699)
|
| Change at Day 2: IL-8 |
11.159
(17.5276)
|
0.236
(5.6791)
|
| Change at Day 8: IL-8 |
-0.470
(3.1986)
|
-2.177
(3.1075)
|
| Change at Day 9: IL-8 |
5.816
(9.5328)
|
-1.685
(4.1328)
|
| Change at Day 15: IL-8 |
-1.959
(5.0839)
|
-1.394
(4.0435)
|
| Baseline (Day 1): IL-10 |
1.784
(5.4054)
|
0.449
(0.1651)
|
| Change at Day 2: IL-10 |
0.081
(0.0969)
|
0.042
(0.1403)
|
| Change at Day 8: IL-10 |
-0.040
(0.2209)
|
0.017
(0.1701)
|
| Change at Day 9: IL-10 |
0.494
(1.2476)
|
0.067
(0.1695)
|
| Change at Day 15: IL-10 |
0.307
(1.0885)
|
-0.013
(0.0531)
|
| Baseline (Day 1): IL-12p70 |
3.280
(0.0000)
|
3.280
(0.0000)
|
| Change at Day 2: IL-12p70 |
0.0000
(0.0000)
|
0.0000
(0.0000)
|
| Change at Day 8: IL-12p70 |
0.0000
(0.0000)
|
0.0000
(0.0000)
|
| Change at Day 9: IL-12p70 |
0.0000
(0.0000)
|
0.0000
(0.0000)
|
| Change at Day 15: IL-12p70 |
0.0000
(0.0000)
|
0.0000
(0.0000)
|
| Baseline (Day 1): TNF-α |
2.856
(0.6101)
|
2.421
(0.6177)
|
| Change at Day 2: TNF-α |
1.218
(1.1446)
|
-0.037
(0.4394)
|
| Change at Day 8: TNF-α |
0.132
(0.5762)
|
0.080
(0.3451)
|
| Change at Day 9: TNF-α |
0.801
(0.7369)
|
-0.043
(0.3940)
|
| Change at Day 15: TNF-α |
0.138
(0.7129)
|
0.083
(0.2492)
|
Adverse Events
| Time Frame | TEAEs are adverse events that started after the first dose of study drug up to Day 35 | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. | |||
| Arm/Group Title | TIMP-GLIA 8 mg/kg | Placebo | ||
| Arm/Group Description | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. | ||
All Cause Mortality |
||||
| TIMP-GLIA 8 mg/kg | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/16 (0%) | 0/18 (0%) | ||
Serious Adverse Events |
||||
| TIMP-GLIA 8 mg/kg | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/16 (0%) | 0/18 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| TIMP-GLIA 8 mg/kg | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/16 (100%) | 18/18 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Microcytic anaemia | 0/16 (0%) | 1/18 (5.6%) | ||
| Cardiac disorders | ||||
| Palpitations | 1/16 (6.3%) | 0/18 (0%) | ||
| Ear and labyrinth disorders | ||||
| Ear pain | 1/16 (6.3%) | 0/18 (0%) | ||
| Vertigo | 1/16 (6.3%) | 0/18 (0%) | ||
| Eye disorders | ||||
| Eye irritation | 1/16 (6.3%) | 0/18 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 0/16 (0%) | 5/18 (27.8%) | ||
| Abdominal distension | 9/16 (56.3%) | 11/18 (61.1%) | ||
| Abdominal pain | 6/16 (37.5%) | 5/18 (27.8%) | ||
| Abdominal pain upper | 2/16 (12.5%) | 3/18 (16.7%) | ||
| Aphthous ulcer | 1/16 (6.3%) | 0/18 (0%) | ||
| Diarrhoea | 8/16 (50%) | 9/18 (50%) | ||
| Erosive duodenitis | 0/16 (0%) | 1/18 (5.6%) | ||
| Eructation | 1/16 (6.3%) | 0/18 (0%) | ||
| Flatulence | 2/16 (12.5%) | 1/18 (5.6%) | ||
| Gastritis | 0/16 (0%) | 1/18 (5.6%) | ||
| Gastritis erosive | 1/16 (6.3%) | 0/18 (0%) | ||
| Gastrointestinal sounds abnormal | 6/16 (37.5%) | 7/18 (38.9%) | ||
| Hiatus hernia | 1/16 (6.3%) | 0/18 (0%) | ||
| Mouth ulceration | 0/16 (0%) | 1/18 (5.6%) | ||
| Nausea | 13/16 (81.3%) | 13/18 (72.2%) | ||
| Oesophageal mucosa erythema | 1/16 (6.3%) | 1/18 (5.6%) | ||
| Vomiting | 5/16 (31.3%) | 6/18 (33.3%) | ||
| Abdominal tenderness | 0/16 (0%) | 1/18 (5.6%) | ||
| General disorders | ||||
| Asthenia | 3/16 (18.8%) | 0/18 (0%) | ||
| Chest discomfort | 2/16 (12.5%) | 0/18 (0%) | ||
| Chills | 1/16 (6.3%) | 1/18 (5.6%) | ||
| Fatigue | 5/16 (31.3%) | 9/18 (50%) | ||
| Feeling abnormal | 0/16 (0%) | 1/18 (5.6%) | ||
| Infections and infestations | ||||
| Pharyngitis | 0/16 (0%) | 1/18 (5.6%) | ||
| Upper respiratory tract infection | 3/16 (18.8%) | 1/18 (5.6%) | ||
| Urinary bladder abscess | 1/16 (6.3%) | 0/18 (0%) | ||
| Viral infection | 0/16 (0%) | 1/18 (5.6%) | ||
| Injury, poisoning and procedural complications | ||||
| Contusion | 1/16 (6.3%) | 1/18 (5.6%) | ||
| Vascular access site haemorrhage | 2/16 (12.5%) | 1/18 (5.6%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 1/16 (6.3%) | 2/18 (11.1%) | ||
| Aspartate aminotransferase increased | 0/16 (0%) | 1/18 (5.6%) | ||
| Blood creatine phosphokinase increased | 1/16 (6.3%) | 0/18 (0%) | ||
| Blood creatinine increased | 0/16 (0%) | 1/18 (5.6%) | ||
| Body temperature increased | 1/16 (6.3%) | 0/18 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 1/16 (6.3%) | 2/18 (11.1%) | ||
| Hyperglycaemia | 1/16 (6.3%) | 0/18 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 0/16 (0%) | 1/18 (5.6%) | ||
| Back pain | 5/16 (31.3%) | 0/18 (0%) | ||
| Myalgia | 1/16 (6.3%) | 0/18 (0%) | ||
| Nervous system disorders | ||||
| Dizziness | 2/16 (12.5%) | 3/18 (16.7%) | ||
| Head discomfort | 1/16 (6.3%) | 0/18 (0%) | ||
| Headache | 7/16 (43.8%) | 3/18 (16.7%) | ||
| Lethargy | 1/16 (6.3%) | 0/18 (0%) | ||
| Paraesthesia | 1/16 (6.3%) | 0/18 (0%) | ||
| Presyncope | 2/16 (12.5%) | 0/18 (0%) | ||
| Psychiatric disorders | ||||
| Insomnia | 1/16 (6.3%) | 0/18 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 1/16 (6.3%) | 0/18 (0%) | ||
| Oropharyngeal pain | 1/16 (6.3%) | 0/18 (0%) | ||
| Throat irritation | 0/16 (0%) | 1/18 (5.6%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Acne | 1/16 (6.3%) | 0/18 (0%) | ||
| Angioedema | 0/16 (0%) | 1/18 (5.6%) | ||
| Hyperhidrosis | 2/16 (12.5%) | 0/18 (0%) | ||
| Pruritus | 2/16 (12.5%) | 1/18 (5.6%) | ||
| Rash | 0/16 (0%) | 1/18 (5.6%) | ||
| Rash generalised | 0/16 (0%) | 1/18 (5.6%) | ||
| Rash pruritic | 1/16 (6.3%) | 0/18 (0%) | ||
| Vascular disorders | ||||
| Flushing | 2/16 (12.5%) | 0/18 (0%) | ||
| Hot flush | 0/16 (0%) | 1/18 (5.6%) | ||
| Hypertension | 1/16 (6.3%) | 0/18 (0%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Takeda |
| Phone | +1-877-825-3327 |
| trialdisclosures@takeda.com |
Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT03738475
Other Study ID Numbers:
- TGLIA-5.002
First Posted:
Nov 13, 2018
Last Update Posted:
Aug 12, 2020
Last Verified:
Jul 1, 2020