TX-SMILE: Texan Allergy & Sinus Center Mountain Cedar Intra-Lymphatic Immunotherapy Study

• Sponsor: Christopher Thompson, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT03682965
• Collaborator: (none)
• Enrollment: 21
• Locations: 3
• Arms: 2
• Actual Duration (Months): 7
• Patients Per Site: 7
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Allergic Rhinitis Due to Tree Pollen; Allergic Conjunctivitis; Allergic Rhinoconjunctivitis	Biological: Intra-lymphatic allergenic extract; Biological: Intra-lymphatic placebo	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Texan Allergy & Sinus Center Mountain Cedar Intra-Lymphatic Immunotherapy Study
• Actual Study Start Date: Sep 28, 2018
• Actual Primary Completion Date: Mar 6, 2019
• Actual Study Completion Date: Apr 29, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: 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.; Other Names: NDC02686614
Placebo Comparator: 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.	Biological: 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.

Outcome Measures

Primary Outcome Measures

1. Average Daily Total Combined Score (TCS) [Up to 4 months]

   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

Secondary Outcome Measures

1. Number of Peak Pollen Season Days With a Lower Group Average Total Combined Score [Assessed up to 4 months, number of actual peak pollen season days was 27]

   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.

2. Patient Reported Pain or Discomfort Following Intra-lymphatic Injections [Immediately after the ILIT procedure]

   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).

3. Patient-reported Treatment Satisfaction at the End of Study [Up to 4 months]

   Percentage of patients reporting satisfaction with their treatment

4. Percentage Change in Allergen-specific Serum IgE [Assessed prior to the first injection and to 4-8 weeks after the end of the 2018-2019 pollen season]

   Percentage change in allergen-specific serum IgE from baseline to the end-of-study visit between active ILIT and placebo.

5. Total Safety Score (TSS) for Active and Placebo Treatment Groups [8 weeks]

   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.

6. 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 [8 weeks]

   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: experience anaphylaxis, or are treated with epinephrine, or experience any other treatment-emergent, serious adverse event (SAE) within 60 minutes of any of the three planned ILIT procedures.

Other Outcome Measures

1. Total Number of Rescue Inhaler Uses by Patients With Asthma [Up to 4 month]

   Relative use of rescue inhalers by patients with comorbid asthma between active and placebo groups during the 2018-2019 Mountain Cedar pollen season.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Both male and female adult patients with a history of Season Allergic Rhinitis (SAR) with bothersome symptoms due to Mountain Cedar pollinosis confirmed using the Modified Quantitate Test (MQT; defined as a wheal greater than or equal to 3 millimeters larger than the diluent control)

2. Patients must be willing to provide written, informed consent

3. Patients must be willing and able to comply with study procedures

4. Women of childbearing potential must agree to use an acceptable form of contraception during the trial

Exclusion Criteria:

1. Patients less than 18 years of age

2. Clinically-significant chronic sinusitis, as determined by the investigator

3. History of anaphylaxis during Mountain Cedar skin prick testing

4. Participation in another clinical trial or use of an experimental medication within 30 days of enrollment

5. 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:

6. Autoimmune diseases, other than allergic rhinitis (AR), stable allergic asthma, eczema and food sensitivities

7. Pulmonary or respiratory diseases other than stable asthma

8. Cancer other than basal cell carcinoma

9. Coronary artery disease or hypertension treated with beta-blockers

10. Clinically significant impairment of renal or hepatic function

11. 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)

12. Previously completed immunotherapy for Mountain Cedar pollinosis, that in the opinion of the investigator would interfere with the assessment or treatment of the patient

13. Inability to access suitable lymph nodes for intralympahtic injections

14. Plans to leave the area for a significant period of the upcoming Mountain Cedar pollen season

15. Pregnant or lactating females

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Texan Allergy & Sinus Center	Austin	Texas	United States	78758
2	Texan Allergy & Sinus Center	Grapevine	Texas	United States	76051
3	Texan Allergy & Sinus Center	San Antonio	Texas	United States	78232

Sponsors and Collaborators

• Christopher Thompson, MD

Investigators

• Principal Investigator: Christopher Thompson, MD, Texan Allergy & Sinus Center

Study Documents (Full-Text)

• Study Protocol - Dec 19, 2018
• Statistical Analysis Plan - Jun 10, 2019
• Informed Consent Form - Dec 24, 2018

More Information

Publications

None provided.

• Responsible Party: Christopher Thompson, MD, Principal Investigator, Texan Allergy & Sinus Center
• ClinicalTrials.gov Identifier: NCT03682965
• Other Study ID Numbers: TASC-ILIT-MC-2018
• First Posted: Sep 25, 2018
• Last Update Posted: Apr 20, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Christopher Thompson, MD, Principal Investigator, Texan Allergy & Sinus Center: Mountain Cedar; Juniperus Ashei; Pollinosis; Intra-lymphatic
• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic; Conjunctivitis; Conjunctivitis, Allergic

Study Results

Participant Flow

Arm/Group Title	Intra-lymphatic Allergenic Extract	Intra-lymphatic Placebo
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	11	10
COMPLETED	11	10
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Intra-lymphatic Allergenic Extract	Intra-lymphatic Placebo	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	11	10	21
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	11 100%	10 100%	21 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	34	32	33
Sex: Female, Male (Count of Participants)
Female	7 63.6%	5 50%	12 57.1%
Male	4 36.4%	5 50%	9 42.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 9.1%	1 10%	2 9.5%
Not Hispanic or Latino	10 90.9%	9 90%	19 90.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	3 27.3%	3 30%	6 28.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	8 72.7%	7 70%	15 71.4%
Region of Enrollment (participants) [Number]
United States	11 100%	10 100%	21 100%

Outcome Measures

1. Primary Outcome

Title	Average Daily Total Combined Score (TCS)
Description	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
Time Frame	Up to 4 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Intra-lymphatic Allergenic Extract	Intra-lymphatic Placebo
Arm/Group Description	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.	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.
Measure Participants	11	10
Mean (Standard Deviation) [units on a scale]	10.1 (3.3)	13.0 (7.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intra-lymphatic Allergenic Extract, Intra-lymphatic Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Kruskal-Wallis
	Comments

2. Secondary Outcome

Title	Number of Peak Pollen Season Days With a Lower Group Average Total Combined Score
Description	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.
Time Frame	Assessed up to 4 months, number of actual peak pollen season days was 27

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intra-lymphatic Allergenic Extract	Intra-lymphatic Placebo
Arm/Group Description	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.	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.
Measure Participants	11	10
Number [days]	20	7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intra-lymphatic Allergenic Extract, Intra-lymphatic Placebo
	Comments	The secondary efficacy endpoint was the percentage of days during peak pollen season for which the average total combined score was lower in the immunotherapy group than in the placebo group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments	The Holm-Bonferroni correction for multiple tests was used because the two outcomes are based on correlated data.
	Method	Clopper-Pearson binomial exact test
	Comments

3. Secondary Outcome

Title	Patient Reported Pain or Discomfort Following Intra-lymphatic Injections
Description	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).
Time Frame	Immediately after the ILIT procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intra-lymphatic Allergenic Extract	Intra-lymphatic Placebo
Arm/Group Description	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.	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.
Measure Participants	11	10
Mean (Standard Deviation) [units on a scale]	0.5 (0.5)	0.5 (0.5)

4. Secondary Outcome

Title	Patient-reported Treatment Satisfaction at the End of Study
Description	Percentage of patients reporting satisfaction with their treatment
Time Frame	Up to 4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intra-lymphatic Allergenic Extract	Intra-lymphatic Placebo
Arm/Group Description	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.	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.
Measure Participants	11	10
Number [percentage of participants]	91 827.3%	90 900%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intra-lymphatic Allergenic Extract, Intra-lymphatic Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Percentage Change in Allergen-specific Serum IgE
Description	Percentage change in allergen-specific serum IgE from baseline to the end-of-study visit between active ILIT and placebo.
Time Frame	Assessed prior to the first injection and to 4-8 weeks after the end of the 2018-2019 pollen season

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intra-lymphatic Allergenic Extract	Intra-lymphatic Placebo
Arm/Group Description	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.	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.
Measure Participants	11	10
Mean (Standard Deviation) [percentage change in serum IgE]	148 (214)	201 (231)

6. Secondary Outcome

Title	Total Safety Score (TSS) for Active and Placebo Treatment Groups
Description	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.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intra-lymphatic Allergenic Extract	Intra-lymphatic Placebo
Arm/Group Description	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.	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.
Measure Participants	11	10
Number [score on a scale]	3	1

7. Secondary Outcome

Title	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
Description	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: experience anaphylaxis, or are treated with epinephrine, or experience any other treatment-emergent, serious adverse event (SAE) within 60 minutes of any of the three planned ILIT procedures.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intra-lymphatic Allergenic Extract	Intra-lymphatic Placebo
Arm/Group Description	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.	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.
Measure Participants	11	10
Count of Participants [Participants]	0 0%	0 0%

8. Other Pre-specified Outcome

Title	Total Number of Rescue Inhaler Uses by Patients With Asthma
Description	Relative use of rescue inhalers by patients with comorbid asthma between active and placebo groups during the 2018-2019 Mountain Cedar pollen season.
Time Frame	Up to 4 month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intra-lymphatic Allergenic Extract	Intra-lymphatic Placebo
Arm/Group Description	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.	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.
Measure Participants	11	10
Number [Rescue Inhaler Uses]	0	0

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	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.
Arm/Group Title	Intra-lymphatic Allergenic Extract		Intra-lymphatic Placebo
Arm/Group Description	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.		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.
All Cause Mortality
	Intra-lymphatic Allergenic Extract		Intra-lymphatic Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/10 (0%)
Serious Adverse Events
	Intra-lymphatic Allergenic Extract		Intra-lymphatic Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Intra-lymphatic Allergenic Extract		Intra-lymphatic Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/11 (45.5%)		1/10 (10%)
Cardiac disorders
hypertension	1/11 (9.1%)	1	0/10 (0%)	0
General disorders
peri-procedural anxiety	1/11 (9.1%)	2	0/10 (0%)	0
Skin and subcutaneous tissue disorders
Injection-site redness	3/11 (27.3%)	3	0/10 (0%)	0
Injection-site bruising	0/11 (0%)	0	1/10 (10%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.