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This is a double-blind, randomized , placebo-controlled study to evaluate the safety and tolerability of AVT001, and to assess AVT001 as a potential treatment for type 1 diabetes (T1D). The trial will involve approximately 24 new-onset T1D subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AVT001 (Treatment) | Experimental | Infusion of AVT001 (treatment) |
|
| Matched placebo | Placebo Comparator | Infusion of AVT001-matched placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AVT001 | Drug | autologous dendritic cell therapy |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAE) | Treatment-emergent AEs (TEAEs) are defined as any AE that started on or after the first dose of study medication through 30 days following the last dose. | At the Primary Analysis (when all the patients have completed their Day 150 visit) |
| Number of Participants and Severity of Local i.v.-Site Reactions, | Number of Participants and severity of local intravenous site reactions after receiving the three doses are reported. | 5 months post first dose |
| Changes From Baseline of Creatinine | Safety/tolerability outcomes - creatinine | 5 months post first dose |
| Changes From Baseline of Aspartate Aminotransferase | Safety/tolerability outcomes - Aspartate Aminotransferase | 5 months post first dose |
| Changes From Baseline of Alanine Aminotransferase | Safety/tolerability outcomes - Alanine Aminotransferase | 5 months post first dose |
| Changes From Baseline of Total Bilirubin | Safety/tolerability outcomes - Total Bilirubin | 5 months post first dose |
| Measure | Description | Time Frame |
|---|---|---|
| Assessment of the HLA-E-restricted CD8+ T Cell Regulatory Activity ("Potency Assay") | CD8+ T cell Inhibition Assay is used to determine whether AVT001 corrects the defect of the dysfunctional Q/E CD8+ Treg pathway in T1D patients. More specifically, this assay detects the specific recognition between the TCR on patients' Q/E CD8+Treg cells and the "common target structure", the HLA-E/Hsp60sp complex, expressed on the surface of the artificially established target cells. The % inhibition measures the function of down-regulation by Q/E CD8+ Tregs via comparing the % of inhibition of TH1 cells versus TB1 cells. By assessing the % inhibition of the TH1 cells of the patient's CD8+ T cells, the CD8+ T cell Inhibition Assay detects the specific recognition of the common target structure (HLA-E/Hsp60sp) on TH1 cells by the TCR on the patient's T cells to be tested. A negative value means the measured Q/E CD8+ Tregs completely lose its inhibition function, and the TH1 cells cultured with it happened to grow faster than the corresponding TB1 cells as its control. |
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Key Inclusion Criteria:
Diagnosis of type 1 diabetes, within 12 months of first dosing, confirmed by positive lab result for one or more of the following types of autoantibodies:
Age 16 or older and able to provide informed consent/assent.
If a participant is female with reproductive potential, willing to avoid pregnancy through the duration of the trial.
Signed and dated written informed consent/assent.
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jason Gaglia, MD | Joslin Diabetes Center, Harvard Medical School | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Joslin Diabetes Center, Harvard Medical School | Boston | Massachusetts | 02215 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38916421 | Result | Gaglia JL, Daley HL, Bryant NK, Ritz J, Dong T, Skyler JS, Jiang H. Novel Autologous Dendritic Cell Therapy AVT001 for Type 1 Diabetes. NEJM Evid. 2024 Jul;3(7):EVIDoa2300238. doi: 10.1056/EVIDoa2300238. Epub 2024 Jun 25. |
| Label | URL |
|---|---|
| Avotres Inc. in collaboration with Joslin Diabetes Center, a Harvard Medical School affiliate, have reported one year data of a phase I/II clinical trial of AVT001 in type 1 diabetes. | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | AVT001 (Treatment) | Infusion of AVT001 (treatment) AVT001: autologous dendritic cell therapy |
| FG001 | Matched Placebo | Infusion of AVT001-matched placebo Placebo: matched placebo |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | AVT001 (Treatment) | Infusion of AVT001 (treatment) AVT001: autologous dendritic cell therapy |
| BG001 | Matched Placebo | Infusion of AVT001-matched placebo Placebo: matched placebo |
| 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 | Number of Participants With Treatment-emergent Adverse Events (TEAE) | Treatment-emergent AEs (TEAEs) are defined as any AE that started on or after the first dose of study medication through 30 days following the last dose. | The safety (SAF) population is defined as all subjects who receive at least one dose of study medication. | Posted | Number | participants | At the Primary Analysis (when all the patients have completed their Day 150 visit) |
|
All anticipated and unanticipated adverse events occured during the study (2 years), including both Treatment Emergent Adverse Events (TEAEs) and Post-Treatment Adverse Events (PTAEs), that exceed a 5% frequency threshold within any arm of the clinical study.
No difference from the clinicaltrials.gov definitions. There has been no death or SAE events recorded throughout the study, and therefore 0 was reported in the following table.
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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 | AVT001 (Treatment) | Infusion of AVT001 (treatment) AVT001: autologous dendritic cell therapy |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| White blood cell count decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Tuochuan Dong, Director, Business & Operations | Avotres Inc. | 7169093370 | tuochuan.dong@avotres.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 1, 2021 | Jul 9, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| Other |
matched placebo |
|
| 5 months post first dose |
| Changes From Baseline in the Area Under the Curve (AUC) of the Stimulated C-peptide Levels Over a 4-hour Mixed Meal Tolerance Test (MMTT) | The area under the stimulated C-peptide curve (AUC) over the first 4-hour period of a mixed meal glucose tolerance test is calculated using the trapezoidal rule that is a weighted sum of the C-peptide values over the 240 minutes. The AUC is normalized by dividing it with 240 mins, therefore, its unit is nmol/L. Missing C-peptide levels at any given timepoint is not imputed. In the calculation of the AUC when C-peptide levels are missing, a line is drawn from the last timepoint with a non-missing C-peptide to the next timepoint with non-missing C-peptide. | 5 months post first dose |
| Changes From Baseline in HbA1c | HbA1c is a blood test that is used to monitor blood glucose control in people with diabetes. HbA1c is short for glycated haemoglobin. The test is also sometimes called haemoglobin A1c. | 5 months post first dose |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
| Primary | Number of Participants and Severity of Local i.v.-Site Reactions, | Number of Participants and severity of local intravenous site reactions after receiving the three doses are reported. | The safety (SAF) population is defined as all subjects who receive at least one dose of study medication. | Posted | Number | Number of patients | 5 months post first dose |
|
|
|
| Primary | Changes From Baseline of Creatinine | Safety/tolerability outcomes - creatinine | The safety (SAF) population is defined as all subjects who receive at least one dose of study medication. | Posted | Mean | Standard Deviation | umol/L | 5 months post first dose |
|
|
|
| Primary | Changes From Baseline of Aspartate Aminotransferase | Safety/tolerability outcomes - Aspartate Aminotransferase | The safety (SAF) population is defined as all subjects who receive at least one dose of study medication. | Posted | Mean | Standard Deviation | U/L | 5 months post first dose |
|
|
|
| Primary | Changes From Baseline of Alanine Aminotransferase | Safety/tolerability outcomes - Alanine Aminotransferase | The safety (SAF) population is defined as all subjects who receive at least one dose of study medication. | Posted | Mean | Standard Deviation | U/L | 5 months post first dose |
|
|
|
| Primary | Changes From Baseline of Total Bilirubin | Safety/tolerability outcomes - Total Bilirubin | The safety (SAF) population is defined as all subjects who receive at least one dose of study medication. | Posted | Mean | Standard Deviation | umol/L | 5 months post first dose |
|
|
|
| Secondary | Assessment of the HLA-E-restricted CD8+ T Cell Regulatory Activity ("Potency Assay") | CD8+ T cell Inhibition Assay is used to determine whether AVT001 corrects the defect of the dysfunctional Q/E CD8+ Treg pathway in T1D patients. More specifically, this assay detects the specific recognition between the TCR on patients' Q/E CD8+Treg cells and the "common target structure", the HLA-E/Hsp60sp complex, expressed on the surface of the artificially established target cells. The % inhibition measures the function of down-regulation by Q/E CD8+ Tregs via comparing the % of inhibition of TH1 cells versus TB1 cells. By assessing the % inhibition of the TH1 cells of the patient's CD8+ T cells, the CD8+ T cell Inhibition Assay detects the specific recognition of the common target structure (HLA-E/Hsp60sp) on TH1 cells by the TCR on the patient's T cells to be tested. A negative value means the measured Q/E CD8+ Tregs completely lose its inhibition function, and the TH1 cells cultured with it happened to grow faster than the corresponding TB1 cells as its control. | The pharmacodynamic (PD) population is defined as all subjects in the safety population with at least one post-baseline assessment for the evaluation of the CD8+ T-cell reg system biomarker. | Posted | Mean | Standard Deviation | Percent of Inhibition | 5 months post first dose |
|
|
|
| Secondary | Changes From Baseline in the Area Under the Curve (AUC) of the Stimulated C-peptide Levels Over a 4-hour Mixed Meal Tolerance Test (MMTT) | The area under the stimulated C-peptide curve (AUC) over the first 4-hour period of a mixed meal glucose tolerance test is calculated using the trapezoidal rule that is a weighted sum of the C-peptide values over the 240 minutes. The AUC is normalized by dividing it with 240 mins, therefore, its unit is nmol/L. Missing C-peptide levels at any given timepoint is not imputed. In the calculation of the AUC when C-peptide levels are missing, a line is drawn from the last timepoint with a non-missing C-peptide to the next timepoint with non-missing C-peptide. | The pharmacodynamic (PD) population is defined as all subjects in the safety population with at least one post-baseline assessment for the evaluation of the CD8+ T-cell reg system biomarker. | Posted | Mean | Standard Deviation | nmol/L | 5 months post first dose |
|
|
|
| Secondary | Changes From Baseline in HbA1c | HbA1c is a blood test that is used to monitor blood glucose control in people with diabetes. HbA1c is short for glycated haemoglobin. The test is also sometimes called haemoglobin A1c. | The pharmacodynamic (PD) population is defined as all subjects in the safety population with at least one post-baseline assessment for the evaluation of the CD8+ T-cell reg system biomarker. | Posted | Mean | Standard Deviation | % of glycated haemoglobin in the blood | 5 months post first dose |
|
|
|
| 0 |
| 16 |
| 0 |
| 16 |
| 16 |
| 16 |
| EG001 | Matched Placebo | Infusion of AVT001-matched placebo Placebo: matched placebo | 0 | 9 | 0 | 9 | 9 | 9 |
| Blood bicarbonate decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
|
| Corona virus infection | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA 22.0 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 22.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 22.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 22.0 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | General disorders | MedDRA 22.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
|
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
|
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
|
| Monocyte count decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA 22.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA 22.0 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA 22.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Attention deficit/hyperactivity disorder | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
|
| Blood potassium decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Enterocolitis infectious | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 22.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Oral papule | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
|
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
|
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| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |