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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-002251-38 | EudraCT Number |
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This study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) triple combination therapy in CF subjects 2 through 5 years of age.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A: ELX/TEZ/IVA | Experimental | Participants weighing greater than or equal to (>=)14 kilograms (kg) at screening received elexacaftor (ELX) 100 milligrams (mg) once daily (qd)/tezacaftor (TEZ) 50 mg qd/ivacaftor (IVA) 75 mg every 12 hours (q12h) in the treatment period for 15 days. |
|
| Part B: ELX/TEZ/IVA | Experimental | Participants weighing (>=)14 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h. Participants weighing (>=)10 kg to less than (<)14 kg received ELX 80 mg qd/TEZ 40 mg qd/IVA 60 mg once every morning (qAM) and 59.5 mg once every evening (qPM) in the treatment period for 24 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ELX/TEZ/IVA | Drug | Fixed dose combination granules for oral administration. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Observed Pre-dose Concentration (Ctrough) of ELX,TEZ,IVA, and Relevant Metabolites | From Day 1 through Day 15 | |
| Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From Day 1 up to Day 43 | |
| Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From Day 1 up to Week 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Part B: Observed Pre-dose Plasma Concentration (Ctrough) of ELX,TEZ,IVA and Relevant Metabolites | From Day 1 through Week 16 | |
| Part B: Absolute Change in Sweat Chloride (SwCl) | Sweat samples were collected using an approved collection device. |
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Key Inclusion Criteria:
Key Exclusion Criteria:
Other protocol defined Inclusion/Exclusion criteria may apply
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Banner University of Arizona Medical Center | Tucson | Arizona | 85724 | United States | ||
| Stanford University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37983082 | Derived | Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4. | |
| 36921081 | Derived |
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Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing
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This study was conducted in participants with cystic fibrosis (CF) aged 2 through 5 years of age (inclusive).
The study was conducted in 2 parts, Part A and Part B. The Participant flow was planned to be presented for the overall treatment arms (i.e. Part A and Part B), irrespective of weight-based dose regimen.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A: ELX/TEZ/IVA | Participants weighing greater than or equals to (>=)14 kg at screening received elexacaftor (ELX) 100 milligrams (mg) once daily (qd)/tezacaftor (TEZ) 50 mg qd/ivacaftor (IVA) 75 mg every 12 hours (q12h) in the treatment period for 15 days. |
| FG001 | Part B: ELX/TEZ/IVA |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part A (15 Days) |
|
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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 | Oct 21, 2021 | May 30, 2023 |
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| IVA | Drug | Granules for oral administration. |
|
|
| From Baseline through Week 24 |
| Part B: Absolute Change in Lung Clearance Index 2.5 (LCI 2.5) | The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry. | From Baseline through Week 24 |
| Palo Alto |
| California |
| 94304 |
| United States |
| Children's Hospital of Colorado | Aurora | Colorado | 80045 | United States |
| Ann & Robert H. Lurie Children's Hospital of Chicago | Chicago | Illinois | 60611 | United States |
| Riley Hospital for Children at Indiana University Health | Indianapolis | Indiana | 46202 | United States |
| Boston Children's Hospital | Boston | Massachusetts | 02115 | United States |
| Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minnesota | Minneapolis | Minnesota | 55404 | United States |
| The Children's Mercy Hospital | Kansas City | Missouri | 64108 | United States |
| Washington University School of Medicine / St. Louis Children's Hospital | St Louis | Missouri | 63110 | United States |
| NC TraCS Institute - CTRC University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
| Oregon Health & Science University | Portland | Oregon | 97239 | United States |
| UPMC Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | 15224 | United States |
| Seattle Children's Hospital | Seattle | Washington | 98105 | United States |
| Telethon Kids Institute | Nedlands | Australia |
| The Royal Children's Hospital | Parkville, VIC | Australia |
| Queensland Children's Hospital | South Brisbane | Australia |
| The Hospital for Sick Children | Toronto | Canada |
| British Columbia Children's Hospital | Vancouver | Canada |
| Charite Paediatric Pulmonology Department | Berlin | Germany |
| Universitatsklinikum Essen (AoR), Kinderklinik III, Abt. fur Pneumologie | Essen | Germany |
| Alder Hey Children's NHS Foundation Trust | Liverpool | United Kingdom |
| Royal Brompton Hospital | London | United Kingdom |
| Goralski JL, Hoppe JE, Mall MA, McColley SA, McKone E, Ramsey B, Rayment JH, Robinson P, Stehling F, Taylor-Cousar JL, Tullis E, Ahluwalia N, Chin A, Chu C, Lu M, Niu T, Weinstock T, Ratjen F, Rosenfeld M. Phase 3 Open-Label Clinical Trial of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged 2-5 Years with Cystic Fibrosis and at Least One F508del Allele. Am J Respir Crit Care Med. 2023 Jul 1;208(1):59-67. doi: 10.1164/rccm.202301-0084OC. |
| 33331662 | Derived | Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3. |
Participants weighing >=14 kg at screening received ELX 100mg qd/TEZ 50mg qd/IVA 75 mg q12h and participants weighing >=10 kg to less than (<)14 kg received ELX 80mg qd/TEZ 40mg qd/IVA 60 mg once every morning (qAM) and IVA 59.5 mg once every evening (qPM) in the treatment period for 24 weeks. |
| COMPLETED |
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| NOT COMPLETED |
|
| Part B (24 Weeks) |
|
|
All participants who received at least one dose of the study drug during the treatment period were included in the baseline analysis.
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| ID | Title | Description |
|---|---|---|
| BG000 | ELX/TEZ/IVA | Part A: Participants weighing greater than or equal to (>=)14 kilograms (kg) at screening received ELX 100 milligrams (mg) once daily (qd)/TEZ 50 mg qd/IVA 75 mg every 12 hours (q12h) in the treatment period for 15 days. Part B: Participants weighing >=14 kg at screening received ELX 100mg qd/TEZ 50mg qd/IVA 75 mg q12h and participants weighing >=10 kg to less than (<)14 kg received ELX 80mg qd/TEZ 40mg qd/IVA 60 mg once every morning (qAM) and IVA 59.5 mg once every evening (qPM) in the treatment period for 24 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | The Baseline data were planned to be presented for the overall treatment arms (i.e. Part A and Part B), irrespective of weight-based dose regimen. Here "number analyzed" signifies participants who were evaluable for specified part of the study. | Count of Participants | Participants |
| |||||||||||||||||
| Sex: Female, Male | The Baseline data were planned to be presented for the overall treatment arms (i.e. Part A and Part B), irrespective of weight-based dose regimen. Here "number analyzed" signifies participants who were evaluable for specified part of the study. | Count of Participants | Participants |
| |||||||||||||||||
| Race/Ethnicity, Customized | The Baseline data were planned to be presented for the overall treatment arms (i.e. Part A and Part B), irrespective of weight-based dose regimen. Here "number analyzed" signifies participants who were evaluable for specified part of the study. | Count of Participants | Participants |
| |||||||||||||||||
| Race/Ethnicity, Customized | The Baseline data were planned to be presented for the overall treatment arms (i.e. Part A and Part B), irrespective of weight-based dose regimen. Here "number analyzed" signifies participants who were evaluable for specified part of the study. | Count of Participants | Participants |
|
| 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 | Part A: Observed Pre-dose Concentration (Ctrough) of ELX,TEZ,IVA, and Relevant Metabolites | Pharmacokinetic (PK) set included participants who received at least 1 dose of study drug. Here the "Number Analyzed" signifies those participants who were evaluable at specified time point. | Posted | Mean | Standard Deviation | micrograms per milliliter (mcg/ml) | From Day 1 through Day 15 |
|
|
| ||||||||||||||||||||||||||||
| Primary | Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Safety set for Part A included all participants who received at least 1 dose of study drug in Part A. This outcome measure was planned only for Part A arm. | Posted | Number | participants | From Day 1 up to Day 43 |
|
| ||||||||||||||||||||||||||||||
| Primary | Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Safety set for Part B included all participants who received at least 1 dose of study drug in Part B. The safety and tolerability analysis for Part B was assessed for the overall treatment arm, irrespective of weight-based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm. | Posted | Number | participants | From Day 1 up to Week 28 |
|
| ||||||||||||||||||||||||||||||
| Secondary | Part B: Observed Pre-dose Plasma Concentration (Ctrough) of ELX,TEZ,IVA and Relevant Metabolites | PK set included participants who received at least 1 dose of study drug. Here the "Number Analyzed" signifies those participants who were evaluable at specified time point. | Posted | Mean | Standard Deviation | micrograms per milliliter (mcg/ml) | From Day 1 through Week 16 |
|
| |||||||||||||||||||||||||||||
| Secondary | Part B: Absolute Change in Sweat Chloride (SwCl) | Sweat samples were collected using an approved collection device. | FAS (Part B). The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight-based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm. | Posted | Least Squares Mean | 95% Confidence Interval | millimole per liter (mmol/L) | From Baseline through Week 24 |
|
| ||||||||||||||||||||||||||||
| Secondary | Part B: Absolute Change in Lung Clearance Index 2.5 (LCI 2.5) | The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry. | FAS (Part B). The efficacy analysis for Part B was assessed for the overall treatment arm, irrespective of weight-based dose regimen. Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm. | Posted | Least Squares Mean | 95% Confidence Interval | index | From Baseline through Week 24 |
|
|
Day 1 Through Safety Follow-up Visit (up to Day 43 for Part A, up to Week 28 for Part B)
The safety analysis for Part B was assessed for the overall treatment arm, irrespective of weight-based dose regimen.Therefore, the analysis is reported for the single triple combination (Part B: ELX/TEZ/IVA) arm.
MedDRA version 23.1 applied for Part A, MedDRA version 25.0 applied for Part B.
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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 | Part A: ELX/TEZ/IVA | Participants weighing >=14 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h in the treatment period for 15 days. | 0 | 18 | 0 | 18 | 15 | 18 |
| EG001 | Part B: ELX/TEZ/IVA | Participants weighing >=14 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h and participants weighing >=10 kg to <14 kg received ELX 80 mg qd/TEZ 40 mg qd/IVA 60 mg qAM and IVA 59.5 mg qPM in the treatment period for 24 weeks. | 0 | 75 | 2 | 75 | 71 | 75 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anal incontinence | Gastrointestinal disorders | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Abnormal behaviour | Psychiatric disorders | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Urinary incontinence | Renal and urinary disorders | MedDRA 23.1,25.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Infective pulmonary exacerbation of cystic fibrosis | Infections and infestations | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Scratch | Injury, poisoning and procedural complications | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| SARS-CoV-2 test positive | Investigations | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Hyperamylasaemia | Metabolism and nutrition disorders | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Hyperlipasaemia | Metabolism and nutrition disorders | MedDRA 23.1,25.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Product taste abnormal | Product Issues | MedDRA 23.1,25.0 | Systematic Assessment |
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| Irritability | Psychiatric disorders | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1,25.0 | Systematic Assessment |
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| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1,25.0 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1,25.0 | Systematic Assessment |
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| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1,25.0 | Systematic Assessment |
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| Papule | Skin and subcutaneous tissue disorders | MedDRA 23.1,25.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23.1,25.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.1,25.0 | Systematic Assessment |
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| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 23.1,25.0 | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 23.1,25.0 | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Monitor | Vertex Pharmaceuticals Incorporated | 617-341-6777 | medicalinfo@vrtx.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 2, 2022 | May 30, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
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| ID | Term |
|---|---|
| C000706587 | elexacaftor, ivacaftor, tezacaftor drug combination |
| C545203 | ivacaftor |
Not provided
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| >=65 years |
|
| Part B |
|
|
| Male |
|
| Part B |
|
|
| Not Hispanic or Latino |
|
| Not collected per local regulations |
|
| Part B |
|
|
| Black or African American |
|
| Not collected per local regulations |
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| Part B |
|
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| Day 15: ELX |
|
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| Day 1: ELX-M23 |
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| Day 8: ELX-M23 |
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| Day 15: ELX-M23 |
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| Day 1: TEZ |
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| Day 8: TEZ |
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| Day 15: TEZ |
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| Day 1: TEZ-M1 |
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| Day 8: TEZ-M1 |
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| Day 15: TEZ-M1 |
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| Day 1: IVA |
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| Day 8: IVA |
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| Day 15: IVA |
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| Day 1: IVA-M1 |
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| Day 8: IVA-M1 |
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| Day 15: IVA-M1 |
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| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| Participants with TEAEs |
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| Participants with SAEs |
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