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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-000903-19 | EudraCT Number |
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Sponsor decision not related to safety concerns
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The primary objective of the study is to evaluate the safety of UX053 in adults with Glycogen Storage Disease Type III (GSD III).
This study is a phase 1/2 first-in-human (FIH), study to evaluate the safety, tolerability, and pharmacokinetic (PK) of a single ascending dose (SAD) and repeat doses (RD) of UX053 in patients with GSD III. The SAD cohorts will be open-label (OL). There will be two types of RD cohorts, an open-label (OL-RD) and a randomized, double-blind (DB), and placebo-controlled (DB-RD).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| UX053 Dose Level 1S ->OL-1R | Experimental | Participants receive a single, peripheral intravenous (IV) infusion of UX053. After completion of the 90-day Follow up Period, participants can enter the open label repeat dose (OL-RD) cohort where they will receive UX053 every 4 weeks (Q4W) for 4 doses. Participants will also receive premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker. |
|
| UX053 Dose Level 2S->OL-2R | Experimental | Participants receive a single, peripheral intravenous (IV) infusion of UX053. After completion of the 90-day Follow up Period, participants can enter the open label repeat dose (OL-RD) cohort where they will receive UX053 every 4 weeks (Q4W) for 4 doses. Participants will also receive premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker. |
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| UX053 Dose Level 3S->OL-3R | Experimental | Participants receive a single, peripheral intravenous (IV) infusion of UX053. After completion of the 90-day Follow up Period, participants can enter the open label repeat dose (OL-RD) cohort where they will receive UX053 every 4 weeks (Q4W) for 4 doses. Participants will also receive premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker. |
|
| UX053 or Placebo Dose Level DB-1R |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| UX053 | Biological | mRNA-based biologic |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE is defined as any AE not present prior to the initiation of the drug treatment or any AE already present that worsens in either intensity or frequency following exposure to the drug treatment. An SAE is an AE that meets any of the following criteria in the view of either the Investigator or Ultragenyx: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; disability/Incapacity; congenital anomaly/birth defect not present at screening; other important medical events. Severity of events were graded as mild (grade1), moderate (grade 2), severe (grade 3), life-threatening (grade 4), or death (grade 5). | From first dose of study drug through the end of study (up to Day 90) |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics (PK) of Amylo-α-1,6-glucosidase 4-alpha-glucanotransferase Messenger Ribonucleic Acid (AGL mRNA) and the Excipient ATX95: Maximum Blood/Plasma Concentration (Cmax) | Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion | |
| PK of AGL mRNA and the Excipient ATX95: Time to Peak Drug Concentration (Tmax) |
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Key Inclusion Criteria:
Inclusion Criteria for Participants Rescreening Into OL-RD Cohorts After Treatment with UX053 in SAD Cohort:
Key Exclusion Criteria:
Exclusion Criteria for Participants Rescreening Into OL-RD Cohorts After Treatment with UX053 in SAD Cohort:
Note: Additional inclusion/exclusion criteria may apply, per protocol
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Ultragenyx Pharmaceutical Inc | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, Irvine | Orange | California | 92868 | United States | ||
| Rare Disease Research |
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| Label | URL |
|---|---|
| Ultragenyx Patient Advocacy/GSD III Disease Information | View source |
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A total of 9 participants enrolled in this study; 1 withdrew consent prior to group assignment, did not receive study drug, and was not included in any data table. Eight participants enrolled and were treated; all completed participation in the single ascending dose (SAD) cohorts and were included in the final analysis. None of these participants were randomized, as they were only in SAD cohorts, and none rolled into an open label-repeated dose cohort, as the study discontinued early.
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| ID | Title | Description |
|---|---|---|
| FG000 | SAD Cohort 1: 0.05 mg/kg | Participants received a single, peripheral intravenous (IV) infusion of a 0.05 mg/kg dose of UX053. |
| FG001 | SAD Cohort 2: 0.10 mg/kg | Participants received a single, peripheral IV infusion of a 0.10 mg/kg dose of UX053. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 14, 2022 | Feb 6, 2024 |
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The SAD and OL-RD cohorts will be open-label, while the DB-RD dose cohorts will be randomized, double-blind, and placebo-controlled.
| Experimental |
Participants randomized to receive a single, peripheral IV infusion of UX053 or Placebo every 2 weeks (Q2W) for 5 doses. Participants will also receive premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker. |
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| UX053 Dose Level DB-2R | Experimental | Participants randomized to receive a single, peripheral IV infusion of UX053 or Placebo every 2 weeks (Q2W) for 5 doses. Participants will also receive premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker. |
|
| UX053 Dose Level DB-3R | Experimental | Participants randomized to receive a single, peripheral IV infusion of UX053 or Placebo every 2 weeks (Q2W) for 5 doses. Participants will also receive premedication, consisting of oral paracetamol/acetaminophen or ibuprofen, an H2 blocker, and an H1 blocker. |
|
| Placebo | Other | consists of the same components as the formulation buffer for UX053 |
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| Antipyretic | Drug | participants will receive oral premedication prior to infusion |
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| H2 Blocker | Drug | participants will receive oral premedication prior to infusion |
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| H1 Blocker | Drug | participants will receive oral premedication prior to infusion |
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| Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion |
| PK of AGL mRNA and the Excipient ATX95: Total Drug Exposure to the Last Measurable Concentration (AUC0-last) | Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion |
| PK of AGL mRNA and the Excipient ATX95: Total Drug Exposure to Infinity (AUC0-inf) | Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion |
| PK of AGL mRNA and the Excipient ATX95: Elimination Half-life (t½) | Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion |
| PK of AGL mRNA and the Excipient ATX95: Clearance (CL) | Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion |
| PK of AGL mRNA and the Excipient ATX95: Volume of Distribution at Steady State (Vss) | Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion |
| Atlanta |
| Georgia |
| 30329 |
| United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| University of Texas, Health Science Center of Houston | Houston | Texas | 77030 | United States |
| Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico | Milan | 20122 | Italy |
| Hospital Universitario 12 de Octubre | Madrid | 28041 | Spain |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | SAD Cohort 1: 0.05 mg/kg | Participants received a single, peripheral intravenous (IV) infusion of a 0.05 mg/kg dose of UX053. |
| BG001 | SAD Cohort 2: 0.10 mg/kg | Participants received a single, peripheral IV infusion of a 0.10 mg/kg dose of UX053. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| 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 (TEAEs), Serious TEAEs, Deaths, Discontinuations, and/or Dose Changes | An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE is defined as any AE not present prior to the initiation of the drug treatment or any AE already present that worsens in either intensity or frequency following exposure to the drug treatment. An SAE is an AE that meets any of the following criteria in the view of either the Investigator or Ultragenyx: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; disability/Incapacity; congenital anomaly/birth defect not present at screening; other important medical events. Severity of events were graded as mild (grade1), moderate (grade 2), severe (grade 3), life-threatening (grade 4), or death (grade 5). | Posted | Count of Participants | Participants | From first dose of study drug through the end of study (up to Day 90) |
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| Secondary | Pharmacokinetics (PK) of Amylo-α-1,6-glucosidase 4-alpha-glucanotransferase Messenger Ribonucleic Acid (AGL mRNA) and the Excipient ATX95: Maximum Blood/Plasma Concentration (Cmax) | Posted | Mean | Standard Deviation | ng/mL | Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion |
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| Secondary | PK of AGL mRNA and the Excipient ATX95: Time to Peak Drug Concentration (Tmax) | Posted | Median | Full Range | hours | Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion |
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| Secondary | PK of AGL mRNA and the Excipient ATX95: Total Drug Exposure to the Last Measurable Concentration (AUC0-last) | Posted | Mean | Standard Deviation | ng*h/mL | Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion |
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| Secondary | PK of AGL mRNA and the Excipient ATX95: Total Drug Exposure to Infinity (AUC0-inf) | Posted | Mean | Standard Deviation | ng*h/mL | Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion |
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| Secondary | PK of AGL mRNA and the Excipient ATX95: Elimination Half-life (t½) | Posted | Mean | Standard Deviation | hours | Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion |
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| Secondary | PK of AGL mRNA and the Excipient ATX95: Clearance (CL) | Posted | Mean | Standard Deviation | mL/h/kg | Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion |
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| Secondary | PK of AGL mRNA and the Excipient ATX95: Volume of Distribution at Steady State (Vss) | Posted | Mean | Standard Deviation | mL/kg | Pre-infusion; 1, 3, 4, 4.5, 5 hr (± 10 min), 6 hr (± 20 min), 8, 10 hr (± 30 min), 24 hr (± 2 hr), 96, 168 hr (± 24 hr), 336, 504, 672 hr (± 48 hr) post-start of infusion |
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Up to 90 days after dosing.
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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 | SAD Cohort 1: 0.05 mg/kg | Participants received a single, peripheral intravenous (IV) infusion of a 0.05 mg/kg dose of UX053. | 0 | 4 | 0 | 4 | 3 | 4 |
| EG001 | SAD Cohort 2: 0.10 mg/kg | Participants received a single, peripheral IV infusion of a 0.10 mg/kg dose of UX053. | 0 | 4 | 0 | 4 | 4 | 4 |
| EG002 | Total | Participants received a single, peripheral IV infusion of a 0.05 or 0.10 mg/kg dose of UX053. | 0 | 8 | 0 | 8 | 7 | 8 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pyrexia | General disorders | MedDRA 25.0 | Systematic Assessment |
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| Seasonal Allergy | Immune system disorders | MedDRA 25.0 | Systematic Assessment |
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| Upper Respiratory Tract Infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
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| Joint Injury | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 25.0 | Systematic Assessment |
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| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Haematoma | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 25.0 | Systematic Assessment |
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| Ear infection bacterial | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Hepatomegaly | Hepatobiliary disorders | MedDRA 25.0 | Systematic Assessment |
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The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Information | Ultragenyx Pharmaceutical Inc | 1-888-756-8567 | medinfo@ultragenyx.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 13, 2023 | Apr 15, 2024 | SAP_001.pdf |
| ID | Term |
|---|---|
| D006010 | Glycogen Storage Disease Type III |
| ID | Term |
|---|---|
| D006008 | Glycogen Storage Disease |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D058633 | Antipyretics |
| D000082 | Acetaminophen |
| D007052 | Ibuprofen |
| D006635 | Histamine H2 Antagonists |
| D015738 | Famotidine |
| D006633 | Histamine Antagonists |
| D017332 | Cetirizine |
| ID | Term |
|---|---|
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000083 | Acetanilides |
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D010666 | Phenylpropionates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D018494 | Histamine Agents |
| D018377 | Neurotransmitter Agents |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006919 | Hydroxyzine |
| D010879 | Piperazines |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Black or African American |
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| Related TEAE |
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| Serious Related TEAE |
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| TEAE With Maximum Severity Grade 5 |
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| TEAE With Maximum Severity Grade 4 |
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| TEAE With Maximum Severity Grade 3 |
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| TEAE With Maximum Severity Grade 2 |
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| TEAE With Maximum Severity Grade 1 |
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| TEAE Leading to Study Discontinuation |
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| TEAE Leading to Treatment Discontinuation |
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| TEAE Leading to Death |
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| TEAE Leading to Dose Reduction |
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| TEAE Leading to Dose Interruption |
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