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Sponsor Decision
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| Name | Class |
|---|---|
| Light Chain Bioscience - Novimmune SA | INDUSTRY |
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Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition characterized by uncontrolled hyperinflammation which may develop on the background of several clinical conditions (e.g. autoimmune disease, infection, malignancy). Emapalumab (previously referred to as NI-0501) is a monoclonal antibody neutralizing interferon-gamma (IFN-gamma), a key cytokine driving the inflammation and tissue damage seen in HLH. The purpose of this study is to assess the efficacy, safety and pharmacokinetics of emapalumab in adult patients with secondary HLH.
Study NI-0501-10 is an open-label, single arm, multicenter, Phase 2/3 interventional study.
The study enrolls adult patients with hemophagocytic lymphohistiocytosis (HLH), specifically newly diagnosed patients with malignancy-associated HLH (M-HLH), and newly diagnosed or previously treated patients with non-malignancy-associated HLH.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Emapalumab | Experimental | Patients were administered Emapalumab-Lzsg by intravenous (i.v.) infusion over a period of 1 to 2 hours, at an initial dose of 6 mg/kg and continued at 3 mg/kg, every 3 days for the first 2 weeks (Study Day [SD] 15), and then twice-a-week. If the treating physician deemed appropriate, the dose of emapalumab could be increased (up to 10 mg/kg), guided by clinical and laboratory response. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Emapalumab-Lzsg | Drug | Patients were administered Emapalumab-Lzsg by intravenous (i.v.) infusion over a period of 1 to 2 hours, at an initial dose of 6 mg/kg and continued at 3 mg/kg, every 3 days for the first 2 weeks (Study Day [SD] 15), and then twice-a-week. If the treating physician deemed appropriate, the dose of emapalumab could be increased (up to 10 mg/kg), guided by clinical and laboratory response. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response | Achievement of either a Complete or Partial Response Complete Response is adjudicated if the following are observed:
Partial Response is adjudicated if there is an improvement (>50% change from baseline or normalization) of at least 3 HLH clinical and laboratory criteria (including Central Nervous System abnormalities). | Week 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Best Response on Treatment | As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description. | Week 4; End of Treatment Visit (on average of 12 weeks) |
| Overall Response |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Radmila Kanceva | Swedish Orphan Biovitrum | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
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The study consisted of a screening (up to 2 weeks), treatment period (until clinically satisfactory response was achieved), and follow-up period (1 year). A total of 7 patients were enrolled in the study and treated.
This Phase 2/3, open-label, single arm study was conducted in adult patients with hemophagocytic lymphohistiocytosis (HLH) at a single center in the United States of America.
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| ID | Title | Description |
|---|---|---|
| FG000 | Emapalumab | Patients were administered emapalumab 6 milligram per kilogram (mg/kg) intravenous (IV) infusion for 1 to 2 hours, and continued at 3 mg/kg every 3 days for the first 2 weeks, and then twice-a-week until clinically satisfactory response was achieved. If the treating physician deemed appropriate, the dose of emapalumab could be increased (up to 10 mg/kg), guided by clinical and laboratory response. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The All Treated analysis set included all patients who received at least 1 dose or 1 incomplete dose of emapalumab.
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| ID | Title | Description |
|---|---|---|
| BG000 | Emapalumab | Patients were administered emapalumab 6 mg/kg IV infusion for 1 to 2 hours, and continued at 3 mg/kg every 3 days for the first 2 weeks, and then twice-a-week until clinically satisfactory response was achieved. If the treating physician deemed appropriate, the dose of emapalumab could be increased (up to 10 mg/kg), guided by clinical and laboratory response. |
| 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 | Overall Response | Achievement of either a Complete or Partial Response Complete Response is adjudicated if the following are observed:
Partial Response is adjudicated if there is an improvement (>50% change from baseline or normalization) of at least 3 HLH clinical and laboratory criteria (including Central Nervous System abnormalities). | Since the study was prematurely terminated, no data was collected for the primary efficacy endpoint. | Posted | No | Week 4 |
|
Treatment-emergent adverse events (TEAEs) reported from the first emapalumab administration up to and including Day+60 study visit were recorded, approximately 13 months.
The All Treated analysis set included all patients who received at least 1 dose or 1 incomplete dose of emapalumab. Only TEAEs are reported.
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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 | Emapalumab | Patients were administered emapalumab 6 mg/kg IV infusion for 1 to 2 hours, and continued at 3 mg/kg every 3 days for the first 2 weeks, and then twice-a-week until clinically satisfactory response was achieved. If the treating physician deemed appropriate, the dose of emapalumab could be increased (up to 10 mg/kg), guided by clinical and laboratory response. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute myeloid leukaemia | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment | Progression of pre-existing condition |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypercoagulation | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
Since the study was prematurely terminated, and considering the low number of patients enrolled, no analysis related to primary and secondary efficacy endpoints and no Pharmacokinetic and Pharmacodynamic summary statistics were performed. Accordingly, no conclusion on the efficacy of emapalumab on this patient population could be withdrawn from the study.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Radmila Kanceva, MD | Sobi | +4686972000 | radmila.kanceva@sobi.com |
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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 | Mar 9, 2020 | Apr 5, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 24, 2021 | Apr 5, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D051359 | Lymphohistiocytosis, Hemophagocytic |
| ID | Term |
|---|---|
| D015616 | Histiocytosis, Non-Langerhans-Cell |
| D015614 | Histiocytosis |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C000644327 | Emapalumab |
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|
|
As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description.
| End of Treatment Visit (on average of 12 weeks) |
| Overall Survival | As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description. | End of Treatment Visit (on average of 12 weeks) |
| Time to Complete Response or Partial Response | As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description. | Week 4; End of Treatment visit (on average of 12 weeks) |
| Duration of Response | As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description. | Up to 1 year after last emapalumab administration |
| Hemophagocytic Lymphohistiocytosis Relapse | As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description. | Up to 1 year after last emapalumab administration |
| Incidence, Severity, Causality and Outcomes of Serious Adverse Events and Non-serious Adverse Events | As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description. | Up to 1 year after last emapalumab administration |
| Serum Concentrations of Emapalumab | As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description. | Up to 1 year after last emapalumab administration |
| Serum Biomarker Levels | Levels of interferon-gamma, C-X-C chemokine ligand 9, soluble CD25, interleukin-6. | Up to 1 year after last emapalumab administration |
| Incidence of Anti-Drug Antibodies Against Emapalumab | As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description. | Up to 1 year after last emapalumab administration |
| Withdrawal by Subject |
|
| Lack of insurance and citizenship |
|
| years |
|
| Age, Continuous | Median | Full Range | years |
|
| Age, Customized | Count of Participants | Participants | No |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
|
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
|
| Region of Enrollment | Count of Participants | Participants | No |
|
| Weight | Mean | Standard Deviation | kg |
|
| Height | Mean | Standard Deviation | centimeter |
|
| OG000 |
| Emapalumab |
Patients were administered emapalumab 6 mg/kg IV infusion for 1 to 2 hours, and continued at 3 mg/kg every 3 days for the first 2 weeks, and then twice-a-week until clinically satisfactory response was achieved. If the treating physician deemed appropriate, the dose of emapalumab could be increased (up to 10 mg/kg), guided by clinical and laboratory response. |
|
| Secondary | Best Response on Treatment | As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description. | Since the study was prematurely terminated, no data was collected for the secondary efficacy endpoints. | Posted | No | Week 4; End of Treatment Visit (on average of 12 weeks) |
|
|
| Secondary | Overall Response | As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description. | Since the study was prematurely terminated, no data was collected for the secondary efficacy endpoints. | Posted | End of Treatment Visit (on average of 12 weeks) |
|
|
| Secondary | Overall Survival | As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description. | Since the study was prematurely terminated, no data was collected for the secondary efficacy endpoints. | Posted | End of Treatment Visit (on average of 12 weeks) |
|
|
| Secondary | Time to Complete Response or Partial Response | As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description. | Since the study was prematurely terminated, no data was collected for the secondary efficacy endpoints. | Posted | Week 4; End of Treatment visit (on average of 12 weeks) |
|
|
| Secondary | Duration of Response | As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description. | Since the study was prematurely terminated, no data was collected for the secondary efficacy endpoints. | Posted | Up to 1 year after last emapalumab administration |
|
|
| Secondary | Hemophagocytic Lymphohistiocytosis Relapse | As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description. | Since the study was prematurely terminated, no data was collected for the secondary efficacy endpoints. | Posted | Up to 1 year after last emapalumab administration |
|
|
| Secondary | Incidence, Severity, Causality and Outcomes of Serious Adverse Events and Non-serious Adverse Events | As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description. | Since the study was prematurely terminated, no data was collected for the secondary safety endpoints. | Posted | Up to 1 year after last emapalumab administration |
|
|
| Secondary | Serum Concentrations of Emapalumab | As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description. | Since the study was prematurely terminated, no data was collected for the secondary Pharmacokinetic endpoints. | Posted | Up to 1 year after last emapalumab administration |
|
|
| Secondary | Serum Biomarker Levels | Levels of interferon-gamma, C-X-C chemokine ligand 9, soluble CD25, interleukin-6. | Since the study was prematurely terminated, no data was collected for the secondary Pharmacodynamic endpoints. | Posted | Up to 1 year after last emapalumab administration |
|
|
| Secondary | Incidence of Anti-Drug Antibodies Against Emapalumab | As no data are reported for this outcome measure, additional method is not applicable in the outcome measure description. | Since the study was prematurely terminated, no data was collected for the secondary Pharmacodynamic endpoints. | Posted | Up to 1 year after last emapalumab administration |
|
|
| 4 |
| 7 |
| 5 |
| 7 |
| 7 |
| 7 |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
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| Lymphoma | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment | Progression of pre-existing condition |
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| Bacteramia | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Cytomegalovirus hepatitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Fungaemia | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Fungal skin infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
|
| Human herpesvirus 6 encephalitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Perineal abscess | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Splenomegaly | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Diverticulum intestinal | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Haematochezia | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Haemorrhoids | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Lip disorder | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
|
| Mouth haemorrhage | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Mouth ulceration | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Mucosal inflammation | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Pain | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Peripheral swelling | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Bacteraemia | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Escherichia bacteramia | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Fungaemia | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Meningitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
|
| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Blood osmolarity increased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Electrocardiogram QT prolonged | Investigations | MedDRA 22.1 | Systematic Assessment |
|
| Transaminases increased | Investigations | MedDRA 22.1 | Systematic Assessment |
|
| Troponin T increased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Hypernatraemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
| Gait disturbance | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
|
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
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| Confusional state | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Hypoaesthesia | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Neuropathy peripheral | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Paresthesia | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Seizure | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Ajustment disorder with depressed mood | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Confusional state | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Irritability | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Mental status changes | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Scrotal swelling | Reproductive system and breast disorders | MedDRA 22.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Skin disorder | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Skin laceration | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Dental disorder prophylaxis | Surgical and medical procedures | MedDRA 22.1 | Systematic Assessment |
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| Penile haemorrhage | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
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