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| Name | Class |
|---|---|
| COUR Pharmaceutical Development Company, Inc. | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TIMP-GLIA | Experimental | 8 mg/kg up to a maximum of 650 mg administered intravenously on days 1 and 8. |
|
| Placebo | Placebo Comparator | Normal saline administered intravenously on days 1 and 8. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TIMP-GLIA | Drug | 8 mg/kg up to a maximum of 650 mg administered intravenously on days 1 and 8. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Interferon-Gamma Spot Forming Units (IFN-gamma SFUs) in a Gliadin-specific Enzyme-linked Immunospot (ELISpot) at 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. | Baseline (Day 15/Day 1), Day 20 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Gliadin-specific T Cell Proliferation by Enzyme-linked Immunosorbent Assay (ELISA) at 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). | Baseline (Day 15/Day 1), Day 20 |
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Key Inclusion Criteria:
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.
6. Vh:Cd ≥ 1.5 on screening biopsy.
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director Clinical Science | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jacksonville Center for Clinical Research | Jacksonville | Florida | 32216 | United States | ||
| Advanced Clinical Research |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33722583 | Derived | Kelly CP, Murray JA, Leffler DA, Getts DR, Bledsoe AC, Smithson G, First MR, Morris A, Boyne M, Elhofy A, Wu TT, Podojil JR, Miller SD; TAK-101 Study Group. TAK-101 Nanoparticles Induce Gluten-Specific Tolerance in Celiac Disease: A Randomized, Double-Blind, Placebo-Controlled Study. Gastroenterology. 2021 Jul;161(1):66-80.e8. doi: 10.1053/j.gastro.2021.03.014. Epub 2021 Mar 17. |
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Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
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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.
Participants took part in the study at 6 investigative sites in the United States from 11 November 2018 to 22 July 2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | TIMP-GLIA 8 mg/kg | TIMP-GLIA 8 milligram per kilogram (mg/kg), infusion, intravenously, once on Days 1 and 8. |
| FG001 | Placebo | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The safety population included all randomized participants who received at least one dose of study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | TIMP-GLIA 8 mg/kg | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. |
| BG001 | Placebo | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Interferon-Gamma Spot Forming Units (IFN-gamma SFUs) in a Gliadin-specific Enzyme-linked Immunospot (ELISpot) at 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. | 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. | Posted | Mean | Standard Deviation | SFUs/10^6 cells PBMC | Baseline (Day 15/Day 1), Day 20 |
|
TEAEs are adverse events that started after the first dose of study drug up to Day 35
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TIMP-GLIA 8 mg/kg | TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Microcytic anaemia | Blood and lymphatic system disorders | MedDRA (21.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | May 14, 2019 | Jun 22, 2020 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Dec 10, 2018 | Jun 22, 2020 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D002446 | Celiac Disease |
| ID | Term |
|---|---|
| D008286 | Malabsorption Syndromes |
| D007410 | Intestinal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D012965 | Sodium Chloride |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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Randomized double-blind placebo-controlled
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| Placebo | Drug | Administered intravenously on days 1 and 8. |
|
|
| Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at 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. |
| Baseline (Day 15/Day 1), Day 20 |
| Change From Baseline in Gut-Homing CD4, CD8 and Gamma Delta T-cells by Mass Cytometry (CyTOF) at 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. | Baseline (Day 15/Day 1), Day 20 |
| Change From Baseline in Ratio of Villus Height to Crypt Depth (Vh:Cd) at 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. | Baseline (Screening), Day 29 |
| Percentage of Participants With Greater Than or Equal to (>=) 0.4 Decrease in Vh:Cd at 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. | Day 29 |
| Change From Baseline in Number of Intestinal Intraepithelial Lymphocytes (IELs) at 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. | Baseline (Screening), Day 29 |
| Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment | 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. | Days 15, 20, 29 and 35 |
| 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 was defined as the last sample collected prior to the first dose of study medication (Screening Period) on Day 1. | Baseline (Screening), Days 8, 15, 20, 29, and 35 |
| Change From Baseline in Serum Complement Levels of C3a and SC5B-9 at Days 2, 8, 9, and 15 | Baseline was defined as the pre-dose value on Day 1. | Baseline (Day 1), Days 2, 8, 9, and 15 |
| Change From Baseline in Serum Complement Levels of C5a at Days 2, 8, 9, and 15 | Baseline was defined as the pre-dose value on Day 1. | Baseline (Day 1) , Days 2, 8, 9, and 15 |
| Change From Baseline in Serum Complement Levels of C1q Binding at Days 15, 20, 29, and 35 | Baseline was defined as the pre-dose value on Day 1. | Baseline (Day 1), Days 15, 20, 29, and 35 |
| 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 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. | Baseline (Day 1), Days 2, 8, 9, and 15 |
| Meridian |
| Idaho |
| 83642 |
| United States |
| Indianapolis Gastroenterology Research Foundation | Indianapolis | Indiana | 46237 | United States |
| Beth Isreal Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| Prism Clinical Research | Saint Paul | Minnesota | 55114 | United States |
| Rapid Medical Research | Beachwood | Ohio | 44122 | United States |
| Advanced Clinical Research | West Jordan | Utah | 84088 | United States |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kilogram per square meter (kg/m^2) |
|
| Disease Duration | Median | Full Range | years |
|
| Gluten Free Diet Duration | Median | Full Range | months |
|
TIMP-GLIA 8 mg/kg, infusion, intravenously, once on Days 1 and 8. |
| OG001 | Placebo | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. |
|
|
|
| Secondary | Change From Baseline in Gliadin-specific T Cell Proliferation by Enzyme-linked Immunosorbent Assay (ELISA) at 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). | 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. | Posted | Mean | Standard Deviation | picogram per milliliter (pg/mL) | Baseline (Day 15/Day 1), Day 20 |
|
|
|
| Secondary | Change From Baseline in Gliadin-specific T Cell Cytokine Secretion by ELISA at 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. | 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. | Posted | Mean | Standard Deviation | pg/mL | Baseline (Day 15/Day 1), Day 20 |
|
|
|
| Secondary | Change From Baseline in Gut-Homing CD4, CD8 and Gamma Delta T-cells by Mass Cytometry (CyTOF) at 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. | 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. | Posted | Mean | Standard Deviation | percent parent | Baseline (Day 15/Day 1), Day 20 |
|
|
|
| Secondary | Change From Baseline in Ratio of Villus Height to Crypt Depth (Vh:Cd) at 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. | 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. | Posted | Mean | Standard Deviation | ratio | Baseline (Screening), Day 29 |
|
|
|
|
| Secondary | Percentage of Participants With Greater Than or Equal to (>=) 0.4 Decrease in Vh:Cd at 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. | 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. | Posted | Number | percentage of participants | Day 29 |
|
|
|
| Secondary | Change From Baseline in Number of Intestinal Intraepithelial Lymphocytes (IELs) at 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. | 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. | Posted | Mean | Standard Deviation | cells per 100 enterocytes | Baseline (Screening), Day 29 |
|
|
|
|
| Secondary | Number of Participants Based on Celiac Symptom Index-Modified (CSI-M) Questionnaire Results by Treatment | 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. | 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. | Posted | Number | participants | Days 15, 20, 29 and 35 |
|
|
|
| Secondary | Plasma Concentrations of TIMP-GLIA | 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. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Day 8: 0 hours (pre-infusion), end of infusion, and at 2 hours post-infusion |
|
|
|
| Secondary | Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | The safety population included all randomized participants who received at least one dose of study medication. | Posted | Count of Participants | Participants | From the first dose of study drug up to Day 35 |
|
|
|
| Secondary | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | The safety population included all randomized participants who received at least one dose of study medication. | Posted | Count of Participants | Participants | From the first dose of study drug up to Day 35 |
|
|
|
| Secondary | Number of Participants With Clinically Significant Change From Baseline in Hematology or Serum Chemistry Laboratory Values | The safety population included all randomized participants who received at least one dose of study medication. | Posted | Count of Participants | Participants | From the first dose of study drug up to Day 35 |
|
|
|
| Secondary | Change From Baseline in Deamidated Gliadin Peptide Immunoglobulin G (DGP-IgG) Antibodies at 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. | 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. | Posted | Mean | Standard Deviation | units | Baseline (Screening), Days 8, 15, 20, 29, and 35 |
|
|
|
| Secondary | Change From Baseline in Serum Complement Levels of C3a and SC5B-9 at Days 2, 8, 9, and 15 | Baseline was defined as the pre-dose value on Day 1. | The safety population included all randomized participants who received at least one dose of study medication. | Posted | Mean | Standard Deviation | ng/mL | Baseline (Day 1), Days 2, 8, 9, and 15 |
|
|
|
| Secondary | Change From Baseline in Serum Complement Levels of C5a at Days 2, 8, 9, and 15 | Baseline was defined as the pre-dose value on Day 1. | The safety population included all randomized participants who received at least one dose of study medication. | Posted | Mean | Standard Deviation | microgram per liter (mcg/L) | Baseline (Day 1) , Days 2, 8, 9, and 15 |
|
|
|
| Secondary | Change From Baseline in Serum Complement Levels of C1q Binding at Days 15, 20, 29, and 35 | Baseline was defined as the pre-dose value on Day 1. | 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. | Posted | Mean | Standard Deviation | units per milliliter (U/mL) | Baseline (Day 1), Days 15, 20, 29, and 35 |
|
|
|
| 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 | 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. | The safety population included all randomized participants who received at least one dose of study medication. | Posted | Mean | Standard Deviation | pg/mL | Baseline (Day 1), Days 2, 8, 9, and 15 |
|
|
|
| 0 |
| 16 |
| 0 |
| 16 |
| 16 |
| 16 |
| EG001 | Placebo | TIMP-GLIA placebo-matching infusion, intravenously, once on Days 1 and 8. | 0 | 18 | 0 | 18 | 18 | 18 |
| Palpitations | Cardiac disorders | MedDRA (21.1) | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA (21.1) | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA (21.1) | Systematic Assessment |
|
| Eye irritation | Eye disorders | MedDRA (21.1) | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Aphthous ulcer | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Erosive duodenitis | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Eructation | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Gastritis erosive | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Gastrointestinal sounds abnormal | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hiatus hernia | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Oesophageal mucosa erythema | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Abdominal tenderness | Gastrointestinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (21.1) | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA (21.1) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (21.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (21.1) | Systematic Assessment |
|
| Feeling abnormal | General disorders | MedDRA (21.1) | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Urinary bladder abscess | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA (21.1) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
|
| Vascular access site haemorrhage | Injury, poisoning and procedural complications | MedDRA (21.1) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Body temperature increased | Investigations | MedDRA (21.1) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (21.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Head discomfort | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA (21.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (21.1) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA (21.1) | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA (21.1) | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (21.1) | Systematic Assessment |
|
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.
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D017670 |
| Sodium Compounds |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
| Change at Day 20 |
|
|
| Change at Day 20: IFN-γ |
|
|
| Baseline (Day 15/Day 1): IL1-β |
|
|
| Change at Day 20: IL1-β |
|
|
| Baseline (Day 15/Day 1): IL-10 |
|
|
| Change at Day 20 :IL-10 |
|
|
| Baseline (Day 15/Day 1): IL-12 |
|
|
| Change at Day 20: IL-12 |
|
|
| Baseline (Day 15/Day 1): IL-13 |
|
|
| Change at Day 20: IL-13 |
|
|
| Baseline (Day 15/Day 1): IL-2 |
|
|
| Change at Day 20: IL-2 |
|
|
| Baseline (Day 15/Day 1): IL-4 |
|
|
| Change at Day 20: IL-4 |
|
|
| Baseline (Day 15/Day 1): IL-6 |
|
|
| Change at Day 20: IL-6 |
|
|
| Baseline (Day 15/Day 1): IL-8 |
|
|
| Change at Day 20: IL-8 |
|
|
| Baseline (Day 15/Day 1): TNF-α |
|
|
| Change at Day 20: TNF-α |
|
|
| Baseline (Day 15/Day 1): CD4 |
|
| Change at Day 20: CD4 |
|
| Baseline (Day 15/Day 1): Gamma Delta T-cells |
|
| Change at Day 20: Gamma Delta T-cells |
|
| D 15, Pain/discomfort in abdomen/stomach: A little |
|
|
| D 15, Pain/discomfort in abdomen/stomach: Some |
|
|
| D 15, Pain/discomfort in abdomen/stomach: Most |
|
|
| D 15, Pain/discomfort in abdomen/stomach: All time |
|
|
| D 15, Nausea: None |
|
|
| D 15, Nausea: A little |
|
|
| D 15, Nausea: Some |
|
|
| D 15, Nausea: Most |
|
|
| D 15, Nausea: All time |
|
|
| D 15, Rumbling in stomach: None |
|
|
| D 15, Rumbling in stomach: A little |
|
|
| D 15, Rumbling in stomach: Some |
|
|
| D 15, Rumbling in stomach: Most |
|
|
| D 15, Rumbling in stomach: All time |
|
|
| D 15, Stomach felt bloated: None |
|
|
| D 15, Stomach felt bloated: A little |
|
|
| D 15, Stomach felt bloated: Some |
|
|
| D 15, Stomach felt bloated: Most |
|
|
| D 15, Stomach felt bloated: All time |
|
|
| D 15, Diarrhea: None |
|
|
| D 15, Diarrhea: A little |
|
|
| D 15, Diarrhea: Some |
|
|
| D 15, Diarrhea: Most |
|
|
| D 15, Diarrhea: All time |
|
|
| D 15, Low energy level: None |
|
|
| D 15, Low energy level: A little |
|
|
| D 15, Low energy level: Some |
|
|
| D 15, Low energy level: Most |
|
|
| D 15, Low energy level: All time |
|
|
| D 20, Pain/discomfort in abdomen/stomach: None |
|
|
| D 20, Pain/discomfort in abdomen/stomach: A little |
|
|
| D 20, Pain/discomfort in abdomen/stomach: Some |
|
|
| D 20, Pain/discomfort in abdomen/stomach: Most |
|
|
| D 20, Pain/discomfort in abdomen/stomach: All time |
|
|
| D 20, Nausea: None |
|
|
| D 20, Nausea: A little |
|
|
| D 20, Nausea: Some |
|
|
| D 20, Nausea: Most |
|
|
| D 20, Nausea: All time |
|
|
| D 20, Rumbling in stomach: None |
|
|
| D 20, Rumbling in stomach: A little |
|
|
| D 20, Rumbling in stomach: Some |
|
|
| D 20, Rumbling in stomach: Most |
|
|
| D 20, Rumbling in stomach: All time |
|
|
| D 20, Stomach felt bloated: None |
|
|
| D 20, Stomach felt bloated: A little |
|
|
| D 20, Stomach felt bloated: Some |
|
|
| D 20, Stomach felt bloated: Most |
|
|
| D 20, Stomach felt bloated: All time |
|
|
| D 20, Diarrhea: None |
|
|
| D 20, Diarrhea: A little |
|
|
| D 20, Diarrhea: Some |
|
|
| D 20, Diarrhea: Most |
|
|
| D 20, Diarrhea: All time |
|
|
| D 20, Low energy level: None |
|
|
| D 20, Low energy level: A little |
|
|
| D 20, Low energy level: Some |
|
|
| D 20, Low energy level: Most |
|
|
| D 20, Low energy level: All time |
|
|
| D 29, Pain/discomfort in abdomen/stomach: None |
|
|
| D 29, Pain/discomfort in abdomen/stomach: A little |
|
|
| D 29, Pain/discomfort in abdomen/stomach: Some |
|
|
| D 29, Pain/discomfort in abdomen/stomach: Most |
|
|
| D 29, Pain/discomfort in abdomen/stomach: All time |
|
|
| D 29, Nausea: None |
|
|
| D 29, Nausea: A little |
|
|
| D 29, Nausea: Some |
|
|
| D 29, Nausea: Most |
|
|
| D 29, Nausea: All time |
|
|
| D 29, Rumbling in stomach: None |
|
|
| D 29, Rumbling in stomach: A little |
|
|
| D 29, Rumbling in stomach: Some |
|
|
| D 29, Rumbling in stomach: Most |
|
|
| D 29, Rumbling in stomach: All time |
|
|
| D 29, Stomach felt bloated: None |
|
|
| D 29, Stomach felt bloated: A little |
|
|
| D 29, Stomach felt bloated: Some |
|
|
| D 29, Stomach felt bloated: Most |
|
|
| D 29, Stomach felt bloated: All time |
|
|
| D 29, Diarrhea: None |
|
|
| D 29, Diarrhea: A little |
|
|
| D 29, Diarrhea: Some |
|
|
| D 29, Diarrhea: Most |
|
|
| D 29, Diarrhea: All time |
|
|
| D 29, Low energy level: None |
|
|
| D 29, Low energy level: A little |
|
|
| D 29, Low energy level: Some |
|
|
| D 29, Low energy level: Most |
|
|
| D 29, Low energy level: All time |
|
|
| D 35, Pain/discomfort in abdomen/stomach: None |
|
|
| D 35, Pain/discomfort in abdomen/stomach: A little |
|
|
| D 35, Pain/discomfort in abdomen/stomach: Some |
|
|
| D 35, Pain/discomfort in abdomen/stomach: Most |
|
|
| D 35, Pain/discomfort in abdomen/stomach: All time |
|
|
| D 35, Nausea: None |
|
|
| D 35, Nausea: A little |
|
|
| D 35, Nausea: Some |
|
|
| D 35, Nausea: Most |
|
|
| D 35, Nausea: All time |
|
|
| D 35, Rumbling in stomach: None |
|
|
| D 35, Rumbling in stomach: A little |
|
|
| D 35, Rumbling in stomach: Some |
|
|
| D 35, Rumbling in stomach: Most |
|
|
| D 35, Rumbling in stomach: All time |
|
|
| D 35, Stomach felt bloated: None |
|
|
| D 35, Stomach felt bloated: A little |
|
|
| D 35, Stomach felt bloated: Some |
|
|
| D 35, Stomach felt bloated: Most |
|
|
| D 35, Stomach felt bloated: All time |
|
|
| D 35, Diarrhea: None |
|
|
| D 35, Diarrhea: A little |
|
|
| D 35, Diarrhea: Some |
|
|
| D 35, Diarrhea: Most |
|
|
| D 35, Diarrhea: All time |
|
|
| D 35, Low energy level: None |
|
|
| D 35, Low energy level: A little |
|
|
| D 35, Low energy level: Some |
|
|
| D 35, Low energy level: Most |
|
|
| D 35, Low energy level: All time |
|
|
|
| 2 hours post infusion |
|
|
| Change at Day 8 |
|
|
| Change at Day 15 |
|
|
| Change at Day 20 |
|
|
| Change at Day 29 |
|
|
| Change at Day 35 |
|
|
| Change at Day 8: C3a |
|
| Change at Day 9: C3a |
|
| Change at Day 15: C3a |
|
| Baseline (Day 1): SC5B-9 |
|
| Change at Day 2: SC5B-9 |
|
| Change at Day 8: SC5B-9 |
|
| Change at Day 9: SC5B-9 |
|
| Change at Day 15: SC5B-9 |
|
| Change at Day 8 |
|
| Change at Day 9 |
|
| Change at Day 15 |
|
| Change at Day 15 |
|
|
| Change at Day 20 |
|
|
| Change at Day 29 |
|
|
| Change at Day 35 |
|
|
| Change at Day 8: IFN-γ |
|
| Change at Day 9: IFN-γ |
|
| Change at Day 15: IFN-γ |
|
| Baseline (Day 1): IL1-β |
|
| Change at Day 2: IL1-β |
|
| Change at Day 8: IL1-β |
|
| Change at Day 9: IL1-β |
|
| Change at Day 15: IL1-β |
|
| Baseline (Day 1): IL-2 |
|
| Change at Day 2: IL-2 |
|
| Change at Day 8: IL-2 |
|
| Change at Day 9: IL-2 |
|
| Change at Day 15: IL-2 |
|
| Baseline (Day 1): IL-4 |
|
| Change at Day 2: IL-4 |
|
| Change at Day 8: IL-4 |
|
| Change at Day 9: IL-4 |
|
| Change at Day 15: IL-4 |
|
| Baseline (Day 1): IL-6 |
|
| Change at Day 2: IL-6 |
|
| Change at Day 8: IL-6 |
|
| Change at Day 9: IL-6 |
|
| Change at Day 15: IL-6 |
|
| Baseline (Day 1): IL-8 |
|
| Change at Day 2: IL-8 |
|
| Change at Day 8: IL-8 |
|
| Change at Day 9: IL-8 |
|
| Change at Day 15: IL-8 |
|
| Baseline (Day 1): IL-10 |
|
| Change at Day 2: IL-10 |
|
| Change at Day 8: IL-10 |
|
| Change at Day 9: IL-10 |
|
| Change at Day 15: IL-10 |
|
| Baseline (Day 1): IL-12p70 |
|
| Change at Day 2: IL-12p70 |
|
| Change at Day 8: IL-12p70 |
|
| Change at Day 9: IL-12p70 |
|
| Change at Day 15: IL-12p70 |
|
| Baseline (Day 1): TNF-α |
|
| Change at Day 2: TNF-α |
|
| Change at Day 8: TNF-α |
|
| Change at Day 9: TNF-α |
|
| Change at Day 15: TNF-α |
|