Tracking Information

First Submitted Date ^ICMJE

September 12, 2018

First Posted Date ^ICMJE

September 25, 2018

Results First Submitted Date ^ICMJE

December 15, 2020

Results First Posted Date ^ICMJE

February 26, 2021

Last Update Posted Date

April 20, 2021

Actual Study Start Date ^ICMJE

September 28, 2018

Actual Primary Completion Date

March 6, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Average Daily Total Combined Score (TCS) [ Time Frame: 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

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Current Secondary Outcome Measures ^ICMJE

Number of Peak Pollen Season Days With a Lower Group Average Total Combined Score [ Time Frame: 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.
Patient Reported Pain or Discomfort Following Intra-lymphatic Injections [ Time Frame: 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).
Patient-reported Treatment Satisfaction at the End of Study [ Time Frame: Up to 4 months ]
Percentage of patients reporting satisfaction with their treatment
Percentage Change in Allergen-specific Serum IgE [ Time Frame: 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.
Total Safety Score (TSS) for Active and Placebo Treatment Groups [ Time Frame: 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.
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 [ Time Frame: 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:
1. experience anaphylaxis, or
2. are treated with epinephrine, or
3. experience any other treatment-emergent, serious adverse event (SAE) within 60 minutes of any of the three planned ILIT procedures.

Original Secondary Outcome Measures ^ICMJE

Proportion of Days in Which Active Patients Experience a Lower Total Combined Score Than Placebo Patients. [ Time Frame: Up to 4 months ]
To evaluate the efficacy of intra-lymphatic immunotherapy relative to placebo during the 2018-2019 Texas Mountain Cedar allergy season based on the proportion of days for which active treatment patients have a lower average total combined score TCS than the placebo patients.
Patient reported pain or discomfort [ Time Frame: Up to 30 minutes post-treatment ]
Patient reported pain will be measured immediately after and 30 minutes post 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).
Patient-reported treatment satisfaction [ Time Frame: Up to 4 months ]
Patient-reported treatment satisfaction at the end of the study using four Likert-style question, PGI-S and two selected questions modified from the Patient Experience Questionnaire (PEQ), "Are you satisfied with the treatment" and "Would you recommend the treatment to your friends or family?"
Change in Allergen-specific Serum IgE [ Time Frame: Up to 4 months ]
Average relative change in allergen-specific IgE baseline to the end-of-study visit between active ILIT and placebo.
Comparison of Average Total Safety Score (TSS) for Active and Placebo Treatment Groups [ Time Frame: 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 is the sum of the patient's score 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.
Relative Safety of ILIT for Mountain Cedar Pollinosis vs Placebo (Proportion of Subjects Who: Experience Anaphylaxis, Treated With Epinephrine, or Experience Any Other Treatment-emergent, (SAE) Within 60 Minutes of Any of Three Planned ILIT Procedures [ Time Frame: 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:
1. experience anaphylaxis, or
2. are treated with epinephrine, or
3. experience any other treatment-emergent, serious adverse event (SAE) within 60 minutes of any of the three planned ILIT procedures.

Current Other Pre-specified Outcome Measures

Total Number of Rescue Inhaler Uses by Patients With Asthma [ Time Frame: 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.

Original Other Pre-specified Outcome Measures

Use of Rescue Inhalers by Patients With Asthma [ Time Frame: 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.

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

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.

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 Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 2

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment

Condition ^ICMJE

Allergic Rhinitis Due to Tree Pollen
Allergic Conjunctivitis
Allergic Rhinoconjunctivitis

Intervention ^ICMJE

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 Name: NDC02686614
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.

Study Arms ^ICMJE

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.

Intervention: Biological: Intra-lymphatic allergenic extract
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.

Intervention: Biological: Intra-lymphatic placebo

Publications *

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.

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Actual Enrollment ^ICMJE

21

Original Estimated Enrollment ^ICMJE

96

Actual Study Completion Date ^ICMJE

April 29, 2019

Actual Primary Completion Date

March 6, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

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)
Patients must be willing to provide written, informed consent
Patients must be willing and able to comply with study procedures
Women of childbearing potential must agree to use an acceptable form of contraception during the trial

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:
1. Autoimmune diseases, other than allergic rhinitis (AR), stable allergic asthma, eczema and food sensitivities
2. Pulmonary or respiratory diseases other than stable asthma
3. Cancer other than basal cell carcinoma
4. Coronary artery disease or hypertension treated with beta-blockers
5. Clinically significant impairment of renal or hepatic function
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

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

No

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT03682965

Other Study ID Numbers ^ICMJE

TASC-ILIT-MC-2018

Has Data Monitoring Committee

No

U.S. FDA-regulated Product

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

IPD Sharing Statement ^ICMJE

Plan to Share IPD:

No

Responsible Party

Christopher Thompson, MD, Texan Allergy & Sinus Center

Study Sponsor ^ICMJE

Christopher Thompson, MD

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Principal Investigator:

Christopher Thompson, MD

Texan Allergy & Sinus Center

PRS Account

Texan Allergy & Sinus Center

Verification Date

March 2021

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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

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