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| ID | Type | Description | Link |
|---|---|---|---|
| JapicCTI-163194 | Other Identifier | JapicCTI |
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| Name | Class |
|---|---|
| Grifols Japan K.K. | OTHER |
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This is a multi-center, open-label study to evaluate the long-term safety of weekly intravenous (IV) infusions of 60 mg/kg alpha1-PI (human), modified process (Alpha-1 MP) in adult participants with Alpha1 Antitrypsin Deficiency (AATD) in Japan who have completed Study GTI1401 (NCT02870309).
This is a multi-center, open-label study to evaluate the long-term safety of weekly IV infusions of 60 mg/kg Alpha-1 MP in adult participants with AATD in Japan who have completed Study GTI1401. Study GTI1401 is being conducted to evaluate the safety and pharmacokinetics (PK) of Alpha-1 MP in participants with AATD in Japan. In the current study, GTI1401-OLE, participants will be administered 60 mg/kg Alpha-1 MP by weekly IV infusion for approximately 1 year (can be renewed annually with the consent of the participants unless the sponsor informs of discontinuation of this OLE trial) to assess the long-term safety of Alpha-1 MP in participants with AATD. This study will be conducted at up to 5 centers in Japan.
At the Week 9 Visit of Study GTI1401, after giving consent, on the same day, participants will be assessed for eligibility at Screening/Extension (Ext) Week 1 Visit for this extension study, Study GTI1401-OLE. If eligible, participants will be administered weekly IV infusions of 60 mg/kg Alpha-1 MP for approximately 1 year or longer. The Week 9 Visit of GTI1401 will be the End of Study Visit for the participants who are enrolled in Study GTI1401-OLE.
Participants in Study GTI1401-OLE will have the option to remain in Study GTI1401-OLE and continue to receive weekly IV infusions of 60 mg/kg Alpha-1 MP for another year or longer. If participants plan to conclude their participation in the study (GTI1401-OLE) early (before Ext. Week 52), participants will be asked to complete the End of Study Follow-Up Assessments, which will be scheduled 4 weeks after the last infusion.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Alpha-1 MP | Experimental | Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alpha-1 MP | Biological | Alpha-1 MP is a stable, sterile, lyophilized preparation of human alpha1-PI, also known as alpha1-antitrypsin. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product or study treatment and which did not necessarily have a causal relationship with this administration. TEAEs were defined as any AE occurring after or on the first Alpha-1 MP infusion until the final visit of study. | From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks) |
| Number of Participants With Adverse Drug Reaction (ADRs) | ADRs were defined as all noxious and unintended responses to a medicinal product or study treatment related to any dose. An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product or study treatment and which did not necessarily have a causal relationship with this administration. | From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks) |
| Number of Participants With Serious Adverse Events (SAEs) | An AE was considered serious in any of the following outcomes or deemed significant for any other reason: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect. | From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks) |
| Number of Participants With Discontinuations Due to Adverse Events (AEs) or Serious Adverse Events (SAEs) | An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product or study treatment and which did not necessarily have a causal relationship with this administration. An AE was considered serious in any of the following outcomes or deemed significant for any other reason: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hiroskai University Hospital | Aomori | 036-8563 | Japan | |||
| Hokkaido University Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35970714 | Derived | Seyama K, Suzuki M, Tasaka S, Nukiwa T, Sato T, Konno S, Sorrells S, Chen J, Aragones ME, Minamino H. Long-term safety of Prolastin(R)-C, an alpha1-proteinase inhibitor, in Japanese patients with alpha1-antitrypsin deficiency. Respir Investig. 2022 Nov;60(6):831-839. doi: 10.1016/j.resinv.2022.07.001. Epub 2022 Aug 12. |
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Participants with diagnosis of alpha1-antitrypsin deficiency (AATD) who completed the Study GTI1401 (NCT02870309) were eligible to enroll in this open-label extension study. The Screening / Extension (Ext) Week 1 Visit and initiation of treatment for the current study (GTI1401-OLE) occurred on the same day as the Week 9 Visit of GTI1401 only for those participants who gave the consent for participation in the Study GTI1401-OLE.
The study was conducted at 3 investigative sites in Japan from 29 July 2016 to 16 February 2021.
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| ID | Title | Description |
|---|---|---|
| FG000 | Alpha-1 MP | Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety Population included all participants who received any amount of Alpha-1 MP.
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| ID | Title | Description |
|---|---|---|
| BG000 | Alpha-1 MP | Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks. |
| 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 (TEAEs) | An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product or study treatment and which did not necessarily have a causal relationship with this administration. TEAEs were defined as any AE occurring after or on the first Alpha-1 MP infusion until the final visit of study. | Safety Population included all participants who received any amount of Alpha-1 MP. | Posted | Count of Participants | Participants | From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks) |
|
From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Safety Population included all participants who received any amount of Alpha-1 MP.
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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 | Alpha-1 MP | Participants received IV infusion of 60 mg/kg Alpha-1 MP administered weekly for mean duration of 213 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arrhythmia | Cardiac disorders | MedDRA 24.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sandra Camprubi | Instituto Grifols SA | +34935710049 | sandra.camprubi@grifols.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 | Jan 21, 2019 | Jan 14, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 26, 2021 | Jan 14, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D019896 | alpha 1-Antitrypsin Deficiency |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C114276 | Mp alpha1 receptor |
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| From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks) |
| Number of Participants With Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | COPD exacerbation was defined as an increase in respiratory symptoms (dyspnea, increased cough, and/or production of sputum) over baseline that usually requires medical intervention. | From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks) |
| Number of Participants With Clinically Significant Findings in Vital Signs | Vital signs included analysis of heart rate, blood pressure, respiratory rate, and temperature. Clinically significant findings in vital signs were based on investigator's discretion. | From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks) |
| Number of Participants With Clinically Significant Findings in Clinical Laboratory Parameters | Clinical laboratory parameters included analysis of hematology, blood chemistry, and urinalysis. Clinically significant findings in clinical laboratory parameters were based on investigator's discretion. | Extension (Ext) Weeks 26, 52, 78, 104, 130, 156,182, 208 (prior to study drug administration) until end of study (Up to 228 weeks) |
| Number of Participants With Clinically Significant Findings in Pulmonary Function Tests (PFTs) | Pulmonary function tests were measured by spirometry. It included Forced Expired Volume in 1 second (FEV1), Forced Vital Capacity (FVC), which were performed according to American Thoracic Society/ European Respiratory Society (ATS/ERS) guidelines. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. PFTs were performed before infusion both pre- and post-bronchodilator administration. The post-bronchodilator PFT was performed 15 to 30 minutes after bronchodilator administration. The same bronchodilator was used throughout the study. Clinically significant findings in pulmonary function tests were based on investigator's discretion. | Extension (Ext) Weeks 26, 52, 78, 104, 130, 156,182, 208 (prior to study drug administration) until end of study (Up to 228 weeks) |
| Trough Levels of Alpha1- Proteinase Inhibitor | Alpha1-PI level was measured by nephelometry. | Extension (Ext) Weeks 12, 24, 36, 48, 64, 76, 88, 100, 116, 128, 140, 152, 168, 180, 192, 204 (prior to study drug administration) until end of study (Up to 228 weeks) |
| Hokkaido |
| 060-8648 |
| Japan |
| Juntendo University Hospital | Tokyo | 113-8431 | Japan |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | Number of Participants With Adverse Drug Reaction (ADRs) | ADRs were defined as all noxious and unintended responses to a medicinal product or study treatment related to any dose. An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product or study treatment and which did not necessarily have a causal relationship with this administration. | Safety Population included all participants who received any amount of Alpha-1 MP. | Posted | Count of Participants | Participants | From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks) |
|
|
|
| Primary | Number of Participants With Serious Adverse Events (SAEs) | An AE was considered serious in any of the following outcomes or deemed significant for any other reason: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect. | Safety Population included all participants who received any amount of Alpha-1 MP. | Posted | Count of Participants | Participants | From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks) |
|
|
|
| Primary | Number of Participants With Discontinuations Due to Adverse Events (AEs) or Serious Adverse Events (SAEs) | An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product or study treatment and which did not necessarily have a causal relationship with this administration. An AE was considered serious in any of the following outcomes or deemed significant for any other reason: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect. | Safety Population included all participants who received any amount of Alpha-1 MP. | Posted | Count of Participants | Participants | From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks) |
|
|
|
| Primary | Number of Participants With Chronic Obstructive Pulmonary Disease (COPD) Exacerbations | COPD exacerbation was defined as an increase in respiratory symptoms (dyspnea, increased cough, and/or production of sputum) over baseline that usually requires medical intervention. | Safety Population included all participants who received any amount of Alpha-1 MP. | Posted | Count of Participants | Participants | From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks) |
|
|
|
| Primary | Number of Participants With Clinically Significant Findings in Vital Signs | Vital signs included analysis of heart rate, blood pressure, respiratory rate, and temperature. Clinically significant findings in vital signs were based on investigator's discretion. | Safety Population included all participants who received any amount of Alpha-1 MP. | Posted | Count of Participants | Participants | From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks) |
|
|
|
| Primary | Number of Participants With Clinically Significant Findings in Clinical Laboratory Parameters | Clinical laboratory parameters included analysis of hematology, blood chemistry, and urinalysis. Clinically significant findings in clinical laboratory parameters were based on investigator's discretion. | Safety Population included all participants who received any amount of Alpha-1 MP. | Posted | Count of Participants | Participants | Extension (Ext) Weeks 26, 52, 78, 104, 130, 156,182, 208 (prior to study drug administration) until end of study (Up to 228 weeks) |
|
|
|
| Primary | Number of Participants With Clinically Significant Findings in Pulmonary Function Tests (PFTs) | Pulmonary function tests were measured by spirometry. It included Forced Expired Volume in 1 second (FEV1), Forced Vital Capacity (FVC), which were performed according to American Thoracic Society/ European Respiratory Society (ATS/ERS) guidelines. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. PFTs were performed before infusion both pre- and post-bronchodilator administration. The post-bronchodilator PFT was performed 15 to 30 minutes after bronchodilator administration. The same bronchodilator was used throughout the study. Clinically significant findings in pulmonary function tests were based on investigator's discretion. | Safety Population included all participants who received any amount of Alpha-1 MP. | Posted | Count of Participants | Participants | Extension (Ext) Weeks 26, 52, 78, 104, 130, 156,182, 208 (prior to study drug administration) until end of study (Up to 228 weeks) |
|
|
|
| Primary | Trough Levels of Alpha1- Proteinase Inhibitor | Alpha1-PI level was measured by nephelometry. | Safety Population included all participants who received any amount of Alpha-1 MP. | Posted | Mean | Standard Deviation | milligram/deciliter (mg/dL) | Extension (Ext) Weeks 12, 24, 36, 48, 64, 76, 88, 100, 116, 128, 140, 152, 168, 180, 192, 204 (prior to study drug administration) until end of study (Up to 228 weeks) |
|
|
|
| 0 |
| 4 |
| 2 |
| 4 |
| 4 |
| 4 |
| Pneumonia | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Large intestine polyp | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA 24.0 | Systematic Assessment |
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| Conjunctival haemorrhage | Eye disorders | MedDRA 24.0 | Systematic Assessment |
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| Eyelid pain | Eye disorders | MedDRA 24.0 | Systematic Assessment |
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| Vitreous floaters | Eye disorders | MedDRA 24.0 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Faeces soft | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Gastrointestinal disorder | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Haemorrhoids | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 24.0 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
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| Arthropod sting | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA 24.0 | Systematic Assessment |
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| Influenza virus test positive | Investigations | MedDRA 24.0 | Systematic Assessment |
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| Gout | Metabolism and nutrition disorders | MedDRA 24.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Pulmonary mass | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Upper respiratory tract inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA 24.0 | Systematic Assessment |
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| Hot flush | Vascular disorders | MedDRA 24.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
|
Site may publish results from the Study, after providing Sponsor thirty days' notice prior to submitting a manuscript or other materials related to the Study to any outside party. At Sponsors' request, Site will remove any Confidential Information (other than Study results), and Site will upon Sponsors' request, delay publication or presentation for a period of up to one hundred twenty days to allow Sponsor to protect its interests in any Sponsor Inventions.
| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D013352 | Subcutaneous Emphysema |
| D004646 | Emphysema |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |