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TX-SMILE is an investigator-initiated, multi-center, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy, safety, and tolerability of intra-lymphatic administration of an approved allergenic extract for the immunotherapy treatment of allergic rhinitis and conjunctivitis due to pollen from the conifer Mountain Cedar.
TX-SMILE is an investigator-initiated, multi-center, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy, safety, and tolerability of an alternative injection site and associated adjustments to dosing and treatment regimen for allergen immunotherapy with a commercially-available, FDA-approved allergenic extract for the immunotherapy treatment of allergic rhinitis and conjunctivitis due to pollen from the conifer Mountain Cedar (Juniperus ashei).
The purpose of this study is to evaluate the effect of a three-dose treatment series of ultrasonography-guided, intra-lymphatic immunotherapy injections over a two-month period prior to the start of the 2018-2019 Mountain Cedar allergy season in central Texas. Patients will be evaluated for safety and tolerability during the treatment period and for efficacy during the 2018-2019 Texas Mountain Cedar pollen season.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intra-lymphatic allergenic extract | Experimental | A series of three injections of 0.1 mL (about 2 drops) of the allergenic extract of Mountain Cedar Pollen given every four weeks into a superficial inguinal lymph node through guidance via ultrasonography using a 1-mL hypodermic syringe with a 25-gauge or smaller needle. |
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| Intra-lymphatic placebo | Placebo Comparator | Diluent as placebo control (sterile saline solution containing 0.4% phenol as a preservative and matched concentration of glycerin) given as a series of three injections of 0.1 mL (about 2 drops) every four weeks into a superficial inguinal lymph node through guidance via ultrasonography using a 1-mL hypodermic syringe with a 25-gauge or smaller needle. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intra-lymphatic allergenic extract | Biological | Mountain Cedar pollen allergenic extract is an FDA-approved, commercially available product for diagnosis and hypo-sensitization treatment of allergies. The labeled use is deep subcutaneous or percutaneous injection. Hyposensitization treatment is typically a series of 30 - 70 injections over 3 - 5 years into the upper aspect of the arm. This investigation is a proof-of-concept study to evaluate an alternative hyposensitization regimen of 3 injections directly into an inguinal lymph node. |
| Measure | Description | Time Frame |
|---|---|---|
| Average Daily Total Combined Score (TCS) | The TCS is the preferred endpoint for rhinoconjunctivitis as recommended by the European Academy of Allergy and Clinical Immunology. Scoring of the TCS is from 0 to 38 on each day that it is assessed. The TCS is the sum of the symptom scores for "runny nose", "stuff nose", "sneezing", "itchy nose", "gritty/itchy eyes", and "watery eyes" rated from no symptoms = 0 to severe symptoms = 3 plus the score for use of rescue medications for allergy symptoms 6 points for oral antihistamine, 6 points for eye drops, and 8 points for a nasal corticosteroid. Thus, a lower score represents fewer symptoms and associated need for allergy medication, while a higher score reflects more severe symptoms and the use of medication to treat symptoms. The TCS will be measured during the 2018-2019 Mountain Cedar pollen se | Up to 4 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Peak Pollen Season Days With a Lower Group Average Total Combined Score | Evaluated during the 2018-2019 Texas Mountain Cedar allergy season. The number of days with a lower group average Total Combined Score, comparatively, in each Arm/Group are reported. Scoring of the TCS is from 0 to 38 on each day that it is assessed.The TCS is the sum of the symptom scores for "runny nose", "stuff nose", "sneezing", "itchy nose", "gritty/itchy eyes", and "watery eyes" rated from no symptoms = 0 to severe symptoms = 3 plus the score for use of rescue medications for allergy symptoms 6 points for oral antihistamine, 6 points for eye drops, and 8 points for a nasal corticosteroid. Thus, a lower score represents fewer symptoms and associated need for allergy medication, while a higher score reflects more severe symptoms and the use of medication to treat symptoms. |
| Measure | Description | Time Frame |
|---|---|---|
| Total Number of Rescue Inhaler Uses by Patients With Asthma | Relative use of rescue inhalers by patients with comorbid asthma between active and placebo groups during the 2018-2019 Mountain Cedar pollen season. | Up to 4 month |
Inclusion Criteria:
Exclusion Criteria:
Patients less than 18 years of age
Clinically-significant chronic sinusitis, as determined by the investigator
History of anaphylaxis during Mountain Cedar skin prick testing
Participation in another clinical trial or use of an experimental medication within 30 days of enrollment
Medically significant co-morbidities that, in the opinion of the investigator, place the subject at increased risk during the study, including but not limited to:
Use of concomitant medications that, in the opinion of the investigator, may reduce the effectiveness of rescue treatments for anaphylaxis (e.g. beta-blockers) or alter the immune response to allergen immunotherapy (e.g., immunosuppressants, systemic corticosteroids)
Previously completed immunotherapy for Mountain Cedar pollinosis, that in the opinion of the investigator would interfere with the assessment or treatment of the patient
Inability to access suitable lymph nodes for intralympahtic injections
Plans to leave the area for a significant period of the upcoming Mountain Cedar pollen season
Pregnant or lactating females
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| Name | Affiliation | Role |
|---|---|---|
| Christopher Thompson, MD | Texan Allergy & Sinus Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Texan Allergy & Sinus Center | Austin | Texas | 78758 | United States | ||
| Texan Allergy & Sinus Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32407947 | Derived | Thompson CP, Silvers S, Shapiro MA. Intralymphatic immunotherapy for mountain cedar pollinosis: A randomized, double-blind, placebo-controlled trial. Ann Allergy Asthma Immunol. 2020 Sep;125(3):311-318.e2. doi: 10.1016/j.anai.2020.04.030. Epub 2020 May 11. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Intra-lymphatic Allergenic Extract | A series of three injections of 0.1 mL (about 2 drops) of the allergenic extract of Mountain Cedar Pollen given every four weeks into a superficial inguinal lymph node through guidance via ultrasonography using a 1-mL hypodermic syringe with a 25-gauge or smaller needle. Intra-lymphatic allergenic extract: Mountain Cedar pollen allergenic extract is an FDA-approved, commercially available product for diagnosis and hypo-sensitization treatment of allergies. The labeled use is deep subcutaneous or percutaneous injection. Hyposensitization treatment is typically a series of 30 - 70 injections over 3 - 5 years into the upper aspect of the arm. This investigation is a proof-of-concept study to evaluate an alternative hyposensitization regimen of 3 injections directly into an inguinal lymph node. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 19, 2018 | Dec 11, 2020 |
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| Intra-lymphatic placebo | Biological | The control group will receive a regimen of 3 injections of diluent (placebo) directly into an inguinal lymph node on the same schedule as the active treatment group. |
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| Assessed up to 4 months, number of actual peak pollen season days was 27 |
| Patient Reported Pain or Discomfort Following Intra-lymphatic Injections | Patient reported pain will be measured immediately after ILIT procedure using the Numeric Rating Scale 11 (NRS-11 rating scale). The NRS-11 asks patients to rate their pain on a scale from 0 (no pain or discomfort) to 11 (worst possible pain). | Immediately after the ILIT procedure |
| Patient-reported Treatment Satisfaction at the End of Study | Percentage of patients reporting satisfaction with their treatment | Up to 4 months |
| Percentage Change in Allergen-specific Serum IgE | Percentage change in allergen-specific serum IgE from baseline to the end-of-study visit between active ILIT and placebo. | Assessed prior to the first injection and to 4-8 weeks after the end of the 2018-2019 pollen season |
| Total Safety Score (TSS) for Active and Placebo Treatment Groups | The total safety score is a is based on World Allergy Organization grading for allergic reactions. Following allergen or placebo exposure via intra-lymphatic injection, patients are monitored for local and systemic allergic reactions for up to 60 minutes post-procedure. At each exposure, a score is rated on a scale from none = 0, local reactions only = 1, mild systemic reactions (WAO Grade 1/2) = 2, moderate systemic reaction (WAO Grade 3) = 3, and severe systemic reaction (WAO grade 4) = 4. The total safety score for each group is the sum of the individual scores of each patient across all three treatments (exposures). Thus, the subject may have a score from 0 to 12 with 0 reflecting no allergic reaction to the allergen and 12 reflecting severe allergic reactions, and the TSS for a group is the sum for all patients in the group. The TSS is used to elicit and grade adverse events of interest rather than for statistical analysis. | 8 weeks |
| Number of Subjects Who: Experienced Anaphylaxis, Were Treated With Epinephrine, or Experienced Any Other Treatment-emergent SAE Within 60 Minutes of Any of Three Planned ILIT Procedures | To evaluate the safety of ILIT for Mountain Cedar pollinosis relative to placebo control based on the proportion of subjects receiving allergenic extract versus the proportion of subjects receiving placebo that:
| 8 weeks |
| Grapevine |
| Texas |
| 76051 |
| United States |
| Texan Allergy & Sinus Center | San Antonio | Texas | 78232 | United States |
| FG001 | Intra-lymphatic Placebo | Diluent as placebo control (sterile saline solution containing 0.4% phenol as a preservative and matched concentration of glycerin) given as a series of three injections of 0.1 mL (about 2 drops) every four weeks into a superficial inguinal lymph node through guidance via ultrasonography using a 1-mL hypodermic syringe with a 25-gauge or smaller needle. Intra-lymphatic placebo: The control group will receive a regimen of 3 injections of diluent (placebo) directly into an inguinal lymph node on the same schedule as the active treatment group. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Intra-lymphatic Allergenic Extract | A series of three injections of 0.1 mL (about 2 drops) of the allergenic extract of Mountain Cedar Pollen given every four weeks into a superficial inguinal lymph node through guidance via ultrasonography using a 1-mL hypodermic syringe with a 25-gauge or smaller needle. Intra-lymphatic allergenic extract: Mountain Cedar pollen allergenic extract is an FDA-approved, commercially available product for diagnosis and hypo-sensitization treatment of allergies. The labeled use is deep subcutaneous or percutaneous injection. Hyposensitization treatment is typically a series of 30 - 70 injections over 3 - 5 years into the upper aspect of the arm. This investigation is a proof-of-concept study to evaluate an alternative hyposensitization regimen of 3 injections directly into an inguinal lymph node. |
| BG001 | Intra-lymphatic Placebo | Diluent as placebo control (sterile saline solution containing 0.4% phenol as a preservative and matched concentration of glycerin) given as a series of three injections of 0.1 mL (about 2 drops) every four weeks into a superficial inguinal lymph node through guidance via ultrasonography using a 1-mL hypodermic syringe with a 25-gauge or smaller needle. Intra-lymphatic placebo: The control group will receive a regimen of 3 injections of diluent (placebo) directly into an inguinal lymph node on the same schedule as the active treatment group. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Average Daily Total Combined Score (TCS) | The TCS is the preferred endpoint for rhinoconjunctivitis as recommended by the European Academy of Allergy and Clinical Immunology. Scoring of the TCS is from 0 to 38 on each day that it is assessed. The TCS is the sum of the symptom scores for "runny nose", "stuff nose", "sneezing", "itchy nose", "gritty/itchy eyes", and "watery eyes" rated from no symptoms = 0 to severe symptoms = 3 plus the score for use of rescue medications for allergy symptoms 6 points for oral antihistamine, 6 points for eye drops, and 8 points for a nasal corticosteroid. Thus, a lower score represents fewer symptoms and associated need for allergy medication, while a higher score reflects more severe symptoms and the use of medication to treat symptoms. The TCS will be measured during the 2018-2019 Mountain Cedar pollen se | Safety analysis included all participants who received at least one dose of study intervention. Efficacy analyses were on the per protocol dataset, which included participants who received three study treatment injections and completed at least 50% of expected electronic diary responses during the allergy season, with no major protocol violations. aLL enrolled patients met the criteria for inclusion in both the safety and per protocol analysis populations | Posted | Mean | Standard Deviation | units on a scale | Up to 4 months |
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| Secondary | Number of Peak Pollen Season Days With a Lower Group Average Total Combined Score | Evaluated during the 2018-2019 Texas Mountain Cedar allergy season. The number of days with a lower group average Total Combined Score, comparatively, in each Arm/Group are reported. Scoring of the TCS is from 0 to 38 on each day that it is assessed.The TCS is the sum of the symptom scores for "runny nose", "stuff nose", "sneezing", "itchy nose", "gritty/itchy eyes", and "watery eyes" rated from no symptoms = 0 to severe symptoms = 3 plus the score for use of rescue medications for allergy symptoms 6 points for oral antihistamine, 6 points for eye drops, and 8 points for a nasal corticosteroid. Thus, a lower score represents fewer symptoms and associated need for allergy medication, while a higher score reflects more severe symptoms and the use of medication to treat symptoms. | Posted | Number | days | Assessed up to 4 months, number of actual peak pollen season days was 27 |
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| Secondary | Patient Reported Pain or Discomfort Following Intra-lymphatic Injections | Patient reported pain will be measured immediately after ILIT procedure using the Numeric Rating Scale 11 (NRS-11 rating scale). The NRS-11 asks patients to rate their pain on a scale from 0 (no pain or discomfort) to 11 (worst possible pain). | Posted | Mean | Standard Deviation | units on a scale | Immediately after the ILIT procedure |
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| Secondary | Patient-reported Treatment Satisfaction at the End of Study | Percentage of patients reporting satisfaction with their treatment | Posted | Number | percentage of participants | Up to 4 months |
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| Secondary | Percentage Change in Allergen-specific Serum IgE | Percentage change in allergen-specific serum IgE from baseline to the end-of-study visit between active ILIT and placebo. | Posted | Mean | Standard Deviation | percentage change in serum IgE | Assessed prior to the first injection and to 4-8 weeks after the end of the 2018-2019 pollen season |
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| Secondary | Total Safety Score (TSS) for Active and Placebo Treatment Groups | The total safety score is a is based on World Allergy Organization grading for allergic reactions. Following allergen or placebo exposure via intra-lymphatic injection, patients are monitored for local and systemic allergic reactions for up to 60 minutes post-procedure. At each exposure, a score is rated on a scale from none = 0, local reactions only = 1, mild systemic reactions (WAO Grade 1/2) = 2, moderate systemic reaction (WAO Grade 3) = 3, and severe systemic reaction (WAO grade 4) = 4. The total safety score for each group is the sum of the individual scores of each patient across all three treatments (exposures). Thus, the subject may have a score from 0 to 12 with 0 reflecting no allergic reaction to the allergen and 12 reflecting severe allergic reactions, and the TSS for a group is the sum for all patients in the group. The TSS is used to elicit and grade adverse events of interest rather than for statistical analysis. | Posted | Number | score on a scale | 8 weeks |
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| Secondary | Number of Subjects Who: Experienced Anaphylaxis, Were Treated With Epinephrine, or Experienced Any Other Treatment-emergent SAE Within 60 Minutes of Any of Three Planned ILIT Procedures | To evaluate the safety of ILIT for Mountain Cedar pollinosis relative to placebo control based on the proportion of subjects receiving allergenic extract versus the proportion of subjects receiving placebo that:
| Posted | Count of Participants | Participants | 8 weeks |
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| Other Pre-specified | Total Number of Rescue Inhaler Uses by Patients With Asthma | Relative use of rescue inhalers by patients with comorbid asthma between active and placebo groups during the 2018-2019 Mountain Cedar pollen season. | Posted | Number | Rescue Inhaler Uses | Up to 4 month |
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From the start of treatment (1st ILIT injection) through the end of the pollen season and for two months therafter, an average of 4 months per participant.
In addition to spontaneous reporting and safety monitoring procedures, including vital signs assessments, Adverse Events of Interest were collected using the Total Safety Score worksheet during each injection procedure.
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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 | Intra-lymphatic Allergenic Extract | A series of three injections of 0.1 mL (about 2 drops) of the allergenic extract of Mountain Cedar Pollen given every four weeks into a superficial inguinal lymph node through guidance via ultrasonography using a 1-mL hypodermic syringe with a 25-gauge or smaller needle. Intra-lymphatic allergenic extract: Mountain Cedar pollen allergenic extract is an FDA-approved, commercially available product for diagnosis and hypo-sensitization treatment of allergies. The labeled use is deep subcutaneous or percutaneous injection. Hyposensitization treatment is typically a series of 30 - 70 injections over 3 - 5 years into the upper aspect of the arm. This investigation is a proof-of-concept study to evaluate an alternative hyposensitization regimen of 3 injections directly into an inguinal lymph node. | 0 | 11 | 0 | 11 | 5 | 11 |
| EG001 | Intra-lymphatic Placebo | Diluent as placebo control (sterile saline solution containing 0.4% phenol as a preservative and matched concentration of glycerin) given as a series of three injections of 0.1 mL (about 2 drops) every four weeks into a superficial inguinal lymph node through guidance via ultrasonography using a 1-mL hypodermic syringe with a 25-gauge or smaller needle. Intra-lymphatic placebo: The control group will receive a regimen of 3 injections of diluent (placebo) directly into an inguinal lymph node on the same schedule as the active treatment group. | 0 | 10 | 0 | 10 | 1 | 10 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection-site redness | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Injection-site bruising | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| hypertension | Cardiac disorders | Systematic Assessment | transient elevation in blood pressure during post-injection monitoring |
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| peri-procedural anxiety | General disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mark Shapiro | Pharma Initiatives | 9193063675 | mshapiro@pharmainitiatives.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 10, 2019 | Dec 11, 2020 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 24, 2018 | Dec 11, 2020 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D003233 | Conjunctivitis, Allergic |
| D006255 | Rhinitis, Allergic, Seasonal |
| ID | Term |
|---|---|
| D003231 | Conjunctivitis |
| D003229 | Conjunctival Diseases |
| D005128 | Eye Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D065631 | Rhinitis, Allergic |
| D012220 | Rhinitis |
| D009668 | Nose Diseases |
| D012140 | Respiratory Tract Diseases |
| D012130 | Respiratory Hypersensitivity |
| D010038 | Otorhinolaryngologic Diseases |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| OG001 | Intra-lymphatic Placebo | Diluent as placebo control (sterile saline solution containing 0.4% phenol as a preservative and matched concentration of glycerin) given as a series of three injections of 0.1 mL (about 2 drops) every four weeks into a superficial inguinal lymph node through guidance via ultrasonography using a 1-mL hypodermic syringe with a 25-gauge or smaller needle. Intra-lymphatic placebo: The control group will receive a regimen of 3 injections of diluent (placebo) directly into an inguinal lymph node on the same schedule as the active treatment group. |
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| OG001 | Intra-lymphatic Placebo | Diluent as placebo control (sterile saline solution containing 0.4% phenol as a preservative and matched concentration of glycerin) given as a series of three injections of 0.1 mL (about 2 drops) every four weeks into a superficial inguinal lymph node through guidance via ultrasonography using a 1-mL hypodermic syringe with a 25-gauge or smaller needle. Intra-lymphatic placebo: The control group will receive a regimen of 3 injections of diluent (placebo) directly into an inguinal lymph node on the same schedule as the active treatment group. |
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Diluent as placebo control (sterile saline solution containing 0.4% phenol as a preservative and matched concentration of glycerin) given as a series of three injections of 0.1 mL (about 2 drops) every four weeks into a superficial inguinal lymph node through guidance via ultrasonography using a 1-mL hypodermic syringe with a 25-gauge or smaller needle.
Intra-lymphatic placebo: The control group will receive a regimen of 3 injections of diluent (placebo) directly into an inguinal lymph node on the same schedule as the active treatment group.
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