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| ID | Type | Description | Link |
|---|---|---|---|
| U01AI100799 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
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Population surveys have shown a positive correlation between increased levels of total serum immunoglobulin E (IgE) and bronchial hyperreactivity. However, it is also clear that exacerbations of asthma are frequently triggered by viral respiratory tract infections, especially those caused by human rhinovirus (RV), also known as the "common cold" virus. This protocol explores the relationship between rhinovirus and allergen/IgE provoked inflammation. Experimental challenges with human (RV) result in more persistent upper respiratory tract symptom scores in asthmatics than in controls. Asthmatics with high levels of IgE also show greater sensitivity to methacholine and higher levels of expired nitric oxide (eNO) than those with low levels of IgE. These data suggest that patients with asthma and high levels of IgE are more likely to have pre-existing inflammation of the airways before virus challenge. This study is being done to determine whether anti-IgE therapy (with omalizumab) will lead to a significant decline in inflammatory biomarkers prior to virus inoculation, and thus reduce the severity of clinical manifestations after an experimental human RV challenge.
The study is a randomized, double-blind placebo controlled study involving a group of 42 mild asthmatics. Subjects will be randomized 1:1 to omalizumab (a humanized monoclonal anti-IgE antibody) or placebo for 8 weeks and then inoculated with rhinovirus (strain-16 produced under GMP conditions and approved for this research by the FDA). Clinical and laboratory (mechanistic) data will be evaluated for 8 weeks before and for 4 weeks after the virus challenge.
The study is being done to test the hypothesis that the reduction of total free IgE in asthmatics treated with omalizumab for 8 weeks prior to and during an experimental RV challenge will lead to a significant decline in lower respiratory tract (chest) symptoms recorded by subjects during the first four days of infection following the challenge compared to lower respiratory tract symptoms recorded during the same period by asthmatic subjects who are treated with placebo.
The primary endpoint will be based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 4 days of acute infection. Diary cards will be scored daily for cough, shortness of breath, chest discomfort and wheezing using a modification of the Jackson criteria. To participate in this study, subjects must live within 90 minutes by car from the University of Virginia.
Note: This protocol has been reviewed and is being monitored for safety by the NIH/NIAID Safety Monitoring Committee and by he IRB at the University of Virginia (IRB-HSR# 14427).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mild asthmatics treated with omalizumab | Active Comparator | Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. |
|
| Mild asthmatics treated with placebo medication | Placebo Comparator | Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| omalizumab | Drug | This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Airway Symptom Scores Experienced by Participants During the First 4 Days of the Acute Infection. | The primary outcome was based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 4 days of acute infection. The symptoms evaluated daily included wheeze, chest tightness, and shortness of breath. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 18. The scores recorded daily could range from 0 to 18. | 4 days |
| Measure | Description | Time Frame |
|---|---|---|
| Airway Symptom Scores Experienced by Participants During the First 7 Days of the Acute Infection. | This secondary outcome was based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 7 days of acute infection. The symptoms evaluated daily included wheeze, chest tightness, and shortness of breath. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 18. The scores recorded daily could range from 0 to 18. |
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Inclusion Criteria:
Participant must be willing to comply with study procedures and requirements.
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Exclusion Criteria:
Hospitalization or treatment in the ER for asthma (unless the treatment involved the use of a bronchodilator only) during the last three years.
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| Name | Affiliation | Role |
|---|---|---|
| Peter W Heymann, MD | University of Virginia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Virginia | Charlottesville | Virginia | 22908 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Mild Asthmatics Treated With Omalizumab | Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA. |
| FG001 | Mild Asthmatics Treated With Placebo Medication | Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Mild Asthmatics Treated With Omalizumab | Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA. |
| 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 | Airway Symptom Scores Experienced by Participants During the First 4 Days of the Acute Infection. | The primary outcome was based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 4 days of acute infection. The symptoms evaluated daily included wheeze, chest tightness, and shortness of breath. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 18. The scores recorded daily could range from 0 to 18. | Two participants in the mild asthmatics treated with omalizumab treatment arm had to be dropped according to protocol because one developed a positive qPCR test for rhinovirus (the virus used for inoculation) 4 weeks before virus inoculation, and the other developed a positive qPCR test for rhinovirus during the week before inoculation. | Posted | Mean | 95% Confidence Interval | units on a scale | 4 days |
|
12 weeks
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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 | Mild Asthmatics Treated With Omalizumab | Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| allergic rhinitis with hoarse voice | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment | Transient |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Peter W. Heymann | University of Virginia | 434-982-3654 | pwh5a@virginia.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 1, 2016 | May 1, 2018 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D000069444 | Omalizumab |
| ID | Term |
|---|---|
| D000888 | Antibodies, Anti-Idiotypic |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
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|
| Rhinovirus (strain 16) | Biological | This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA. |
|
| 7 days |
| Airway Symptom Scores Experienced by Participants During the 21 Days of Monitoring During the Infection. | This secondary outcome was based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the 21 days of monitoring during the infection. The symptoms evaluated daily included wheeze, chest tightness, and shortness of breath. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 18. The scores recorded daily could range from 0 to 18. | 21 days |
| Airway Symptom Scores Experienced by Participants During the First 4 Days of the Acute Infection With Cough. | This secondary outcome was based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 4 days of acute infection. The symptoms evaluated daily included wheeze, chest tightness, shortness of breath and cough. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 24. The scores recorded daily could range from 0 to 24. | 4 days |
| Airway Symptom Scores Experienced by Participants During the First 4 Days of the Acute Infection (Upper Respiratory Tract Symptoms). | This secondary outcome was based on the comparison of cumulative upper respiratory tract symptoms scores (CURTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 4 days of acute infection. The symptoms evaluated daily included runny nose, sneezing, nasal congestion, sore throat, headache, chills/fever, fatigue, itchy/watery eyes. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 48. The scores recorded daily could range from 0 to 48. | 4 days |
| Number of Participants Whose FEV1 Dropped by More Than 20% During the Infection. | Number of participants whose FEV1 dropped by more than 20% during the infection compared to their FEV1 value at baseline at the time of enrollment. | 21 days |
| Lung function exclusion criteria |
|
| Tested positive for virus during run-in |
|
| BG001 | Mild Asthmatics Treated With Placebo Medication | Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Total serum IgE level (IU/ml) | Geometric Mean | Full Range | IU/ml |
|
| Negative serum neutralizing antibody to rhinovirus-16 | Count of Participants | Participants |
|
| OG000 | Mild Asthmatics Treated With Omalizumab | Subjects with mild asthma will be treated with omalizumab for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. Omalizumab will be given subcutaneously every 2 to 4 weeks according to the manufacturer's recommendations. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA. |
| OG001 | Mild Asthmatics Treated With Placebo Medication | Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA. |
|
|
|
| Secondary | Airway Symptom Scores Experienced by Participants During the First 7 Days of the Acute Infection. | This secondary outcome was based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 7 days of acute infection. The symptoms evaluated daily included wheeze, chest tightness, and shortness of breath. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 18. The scores recorded daily could range from 0 to 18. | Two participants in the mild asthmatics treated with omalizumab treatment arm had to be dropped according to protocol because one developed a positive qPCR test for rhinovirus (the virus used for inoculation) 4 weeks before virus inoculation, and the other developed a positive qPCR test for rhinovirus during the week before inoculation. | Posted | Mean | 95% Confidence Interval | units on a scale | 7 days |
|
|
|
|
| Secondary | Airway Symptom Scores Experienced by Participants During the 21 Days of Monitoring During the Infection. | This secondary outcome was based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the 21 days of monitoring during the infection. The symptoms evaluated daily included wheeze, chest tightness, and shortness of breath. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 18. The scores recorded daily could range from 0 to 18. | Two participants in the mild asthmatics treated with omalizumab treatment arm had to be dropped according to protocol because one developed a positive qPCR test for rhinovirus (the virus used for inoculation) 4 weeks before virus inoculation, and the other developed a positive qPCR test for rhinovirus during the week before inoculation. | Posted | Mean | 95% Confidence Interval | units on a scale | 21 days |
|
|
|
|
| Secondary | Airway Symptom Scores Experienced by Participants During the First 4 Days of the Acute Infection With Cough. | This secondary outcome was based on the comparison of cumulative lower respiratory tract symptoms scores (CLRTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 4 days of acute infection. The symptoms evaluated daily included wheeze, chest tightness, shortness of breath and cough. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 24. The scores recorded daily could range from 0 to 24. | Two participants in the mild asthmatics treated with omalizumab treatment arm had to be dropped according to protocol because one developed a positive qPCR test for rhinovirus (the virus used for inoculation) 4 weeks before virus inoculation, and the other developed a positive qPCR test for rhinovirus during the week before inoculation. | Posted | Mean | 95% Confidence Interval | units on a scale | 4 days |
|
|
|
|
| Secondary | Airway Symptom Scores Experienced by Participants During the First 4 Days of the Acute Infection (Upper Respiratory Tract Symptoms). | This secondary outcome was based on the comparison of cumulative upper respiratory tract symptoms scores (CURTS) in the asthmatic subjects treated with omalizumab compared to those treated with placebo over the first 4 days of acute infection. The symptoms evaluated daily included runny nose, sneezing, nasal congestion, sore throat, headache, chills/fever, fatigue, itchy/watery eyes. Symptom scores were recorded by subjects twice daily (in the morning and evening). Each symptom was scored on a scale of 1 to 3. Therefore, the total maximum (worst) score for a day would be 48. The scores recorded daily could range from 0 to 48. | Two participants in the mild asthmatics treated with omalizumab treatment arm had to be dropped according to protocol because one developed a positive qPCR test for rhinovirus (the virus used for inoculation) 4 weeks before virus inoculation, and the other developed a positive qPCR test for rhinovirus during the week before inoculation. | Posted | Mean | 95% Confidence Interval | units on a scale | 4 days |
|
|
|
|
| Secondary | Number of Participants Whose FEV1 Dropped by More Than 20% During the Infection. | Number of participants whose FEV1 dropped by more than 20% during the infection compared to their FEV1 value at baseline at the time of enrollment. | Two participants in the omalizumab treatment arm had to be dropped according to protocol because 1 developed a positive qPCR test for rhinovirus 4 weeks before virus inoculation, and the other developed a positive qPCR test for rhinovirus during the week before inoculation. | Posted | Count of Participants | Participants | 21 days |
|
|
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| Post-Hoc | Time to Peak Airway Symptoms (Lower Respiratory Tract) Following Virus Inoculation. | Time to peak airway symptoms (lower respiratory tract) following virus inoculation was compared among the asthmatics in the omalizumab treatment arm compared to time to peak symptoms among those in the placebo treatment arm. | Two participants in the mild asthmatics treated with omalizumab treatment arm had to be dropped according to protocol because one developed a positive qPCR test for rhinovirus (the virus used for inoculation) 4 weeks before virus inoculation, and the other developed a positive qPCR test for rhinovirus during the week before inoculation. | Posted | Geometric Mean | 95% Confidence Interval | days | 21 days |
|
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| 5 |
| 15 |
| EG001 | Mild Asthmatics Treated With Placebo Medication | Subjects with mild asthma will be treated with placebo medication for 8 weeks before and for 3 weeks after an experimental challenge with rhinovirus. The placebo mediation will consist of the same diluent used for suspending the omalizumab without omalizumab added. omalizumab: This medication has been approved for clinical use to treat patients with moderate to severe asthma by the FDA in 2003 and for use in this study (BB-IND# 10510) Rhinovirus (strain 16): This strain of pooled rhinovirus has been approved for use in experimental challenges (BB-IND# 15162) and for use in this study (BB-IND# 10510) by the FDA. | 0 | 16 | 0 | 16 | 4 | 16 |
|
| Laryngitis | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment | Transient |
|
| Anemia (low hemoglobin) | Blood and lymphatic system disorders | MedDRA 10.0 | Systematic Assessment | Three subjects were dropped before the rhinovirus challenge. Their anemia was mild, but Hb level was < 10.0 gm/dL. They were seen by a doctor at the University of Virginia (student health). |
|
| Bronchitis | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment | Transient |
|
| Insomnia | General disorders | MedDRA 10.0 | Systematic Assessment | Episodic (3 times), but transient |
|
| Mild concusion | Injury, poisoning and procedural complications | MedDRA 10.0 | Systematic Assessment | Occurred during the Run-in period. Event causing the concussion was unrelated to the study. |
|
| Blood neutropenia | Blood and lymphatic system disorders | MedDRA 10.0 | Systematic Assessment | Blood neutropenia (< 1500 cells/mm3) occurred twice after rhinovirus was administered. The neutropenia resolved before the subject completed the study. |
|
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| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D001798 |
| Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D012712 | Serum Globulins |
| D005916 | Globulins |