Clinical trial NCT04676763: Substance P Challenge in Healthy Participants
Official title: An Open Label, Single Centre, Enabling Study to Investigate the Optimum Method for Use of Intradermal Substance P as a Challenge Agent in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Skin Diseases
Keywords: Substance P
Wheal response
Flare response
Skin challenge
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2020-12-21
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Parts 1 and 2 will run sequentially. Part 1 will include 1 challenge visit; Part 2 will include two challenge visits.
Primary purpose: OTHER

Brief summary: The objectives of this enabling study are to characterize the wheal and flare responses over time following skin challenges with ascending concentrations of Substance P. This will be a 2-part study: Part 1 will aid in the understanding of the wheal and flare responses following Substance P. Part 2 will investigate the variability of the responses. Participants may be enrolled into Part 1 or Part 2, not both.


Eligibility criteria: Inclusion criteria:

* 18 to 50 years of age inclusive.
* Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, ECGs and vital signs.
* Participants who responded positive to histamine skin prick test and negative to saline injection at screening.
* Participants with Fitzpatrick skin type I-II (Caucasian).
* Body weight greater than or equal to (\>=) 50 kilogram (kg) and body mass index (BMI) within the range 19-29.9 kilogram per meter square (kg/m2) (inclusive).
* Male participants are eligible to participate in the study.
* A female participant is eligible to participate if she is not pregnant or breastfeeding or using highly effective contraceptive methods. Woman of non-childbearing potential can also participate.
* A sensitive pregnancy test is required to be negative on the day of each challenge.
* Capable of giving signed informed consent.

Exclusion Criteria:

* Significant history of or current, cardiovascular (including hypotension, severe hypertension, vasomotor instability), respiratory (including asthma), renal, gastrointestinal, endocrine, hematological, infectious or neurological disorders constituting a risk when taking part in the study or interfering with the interpretation of data.
* History or presence of significant skin disorder (such as but not limited to chronic urticaria, atopic dermatitis, severe eczema, psoriasis or skin cancer).
* History of risk for or actual experience of complications from skin biopsy including excess bleeding, infection, or scarring/keloid formation.
* Abnormal blood pressure as determined by the investigator.
* Alanine transaminase (ALT) \>1.5 times upper limit of normal (ULN).
* Total bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if total bilirubin is fractionated and direct bilirubin \<35%).
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
* QT interval corrected for heart rate according to Fridericia's formula (QTcF) \>450 millisecond (msec), based on the mean of triplicate ECGs.
* Use of any form of H1 or H2 antihistamine, tricyclic antidepressants, beta2 agonists, dopamine, or beta blocking agents within 14 days before the first challenge visit through final assessments.
* Use of topical medications such as but not limited to retinoids, steroids, and transdermal hormone replacement therapies on or near the intended site of application within 8 weeks prior to dosing through treatment follow up. Use of other topical preparations such as those containing vitamins, supplements or herbal within 2 weeks prior to dosing through treatment follow up.
* Past or intended use of any other non-topical over-the-counter or prescription medication, including herbal medications, within 7 days before the first challenge visit, unless, in the opinion of the investigator and GlaxoSmithKline medical monitor, the medication will not constitute a risk when taking the study intervention or interfere with the interpretation of data.
* Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 3 months.
* Current enrolment in any clinical study involving an investigational study intervention or any other type of medical research.
* Current enrolment or past participation in this study.
* Presence of Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HbcAb) at screening or within 3 months before the first challenge day.
* Positive Hepatitis C antibody test result at screening or within 3 months before the first challenge day.
* Positive Hepatitis C RNA test result at screening or within 3 months before the first challenge day.
* Positive pre-study drug/alcohol screen.
* Positive human immunodeficiency virus (HIV) antibody test at screening or within 3 months before the first challenge day.
* Current use of known drugs of abuse.
* Participants who present with damaged skin including sunburn, scar tissue, moles, uneven skin tones and dark skin tone (Fitzpatrick\>2), tattoos, body piercings, branding or other skin disfiguration on or near the intended site of application which could interfere with the assessments
* Regular alcohol consumption within 6 months before the study defined as an average weekly intake of \>21 units for males or \>14 units for females.
* Smoking test result indicative of smoking, history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
* Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
* Unable to refrain from the use of topical medications from before the first to after the last challenge visit.

Primary outcomes:
measure: Part 1: Wheal Response-time Area Under the Curve (AUC) Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1)
timeFrame: 0, 5, 10, 15, 20, 40, 60, 90 and 120 minutes post-challenge on Day 1 (Visit 1)
measure: Part 2: Wheal Response-time AUC Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)
timeFrame: 0, 5, 10, 15, 20, 30, 40, 60, 90 and 120 minutes post-challenge on Day 1 (Visit 1) and on Week 2 (Visit 2)
Secondary outcomes:
measure: Part 1: Maximum Observed Wheal Area Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1)
timeFrame: 2 hours post-challenge on Day 1 (Visit 1)
measure: Part 2: Maximum Observed Wheal Area Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P Across- at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)
timeFrame: 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge at Week 2 (Visit 2)
measure: Part 1: Time to Maximum Observed Wheal Area Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1)
timeFrame: 2 hours post-challenge on Day 1 (Visit 1)
measure: Part 2: Time to Maximum Observed Wheal Area Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)
timeFrame: 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge at Week 2 (Visit 2)
measure: Part 1: Time to Complete Wheal Area Disappearance Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1)
timeFrame: 2 hours post-challenge on Day 1 (Visit 1)
measure: Part 2: Time to Complete Wheal Area Disappearance Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)
timeFrame: 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge at Week 2 (Visit 2)
measure: Part 1: Flare Response-time AUC Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1)
timeFrame: 0, 5, 10, 15, 20, 40, 60, 90 and 120 minutes post-challenge on Day 1 (Visit 1)
measure: Part 2: Flare Response-time AUC Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)
timeFrame: 0, 5, 10, 15, 20, 30, 40, 60, 90 and 120 minutes post-challenge on Day 1 (Visit 1) and on Week 2 (Visit 2)
measure: Part 1: Maximum Observed Flare Area Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1)
timeFrame: 2 hours post-challenge on Day 1 (Visit 1)
measure: Part 2: Maximum Observed Flare Area Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P Across- at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)
timeFrame: 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge At Week 2 (Visit 2)
measure: Part 1: Time to Maximum Observed Flare Area Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1)
timeFrame: 2 hours post-challenge on Day 1 (Visit 1)
measure: Part 2: Time to Maximum Observed Flare Area Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)
timeFrame: 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge At Week 2 (Visit 2)
measure: Part 1: Time to Complete Flare Area Disappearance Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1)
timeFrame: 2 hours post-challenge on Day 1 (Visit 1)
measure: Part 2: Time to Complete Flare Area Disappearance Over the 2 Hours Post-challenge Period Following Skin Challenge With Substance P- at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)
timeFrame: 2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge At Week 2 (Visit 2)
measure: Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)- Substance P Only
timeFrame: Up to Day 1
measure: Part 2: Number of Participants With Non-serious AEs and SAEs- Substance P Only
timeFrame: Up to 3 weeks
measure: Part 1: Number of Participants With Worst Case Vital Signs Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 1 (Day 1)
timeFrame: At Day 1 (Visit 1)
measure: Part 2: Number of Participants With Worst Case Vital Signs Parameter Results by Potential Clinical Importance (PCI) Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)
timeFrame: At Day 1 (Visit 1) and Week 2 (Visit 2)
measure: Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophil Count, Platelet Count and White Blood Cell Count- Substance P Only at Challenge Visit 1 (Day 1)
timeFrame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
measure: Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophil Count, Platelet Count and White Blood Cell Count- Substance P Only at Challenge Visit 2 (Week 2)
timeFrame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
measure: Part 1: Change From Baseline in Hematology Parameter: Hemoglobin- Substance P Only at Challenge Visit 1 (Day 1)
timeFrame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
measure: Part 2: Change From Baseline in Hematology Parameter: Hemoglobin- Substance P Only at Challenge Visit 2 (Week 2)
timeFrame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
measure: Part 1: Change From Baseline in Hematology Parameter: Hematocrit- Substance P Only at Challenge Visit 1 (Day 1)
timeFrame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
measure: Part 2: Change From Baseline in Hematology Parameter: Hematocrit- Substance P Only at Challenge Visit 2 (Week 2)
timeFrame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
measure: Part 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin- Substance P Only at Challenge Visit 1 (Day 1)
timeFrame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
measure: Part 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin- Substance P Only at Challenge Visit 2 (Week 2)
timeFrame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
measure: Part 1: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume- Substance P Only at Challenge Visit 1 (Day 1)
timeFrame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
measure: Part 2: Change From Baseline in Hematology Parameter: Mean Corpuscle Volume- Substance P Only at Challenge Visit 2 (Week 2)
timeFrame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
measure: Part 1: Change From Baseline in Hematology Parameter: Red Blood Cell Count- Substance P Only at Challenge Visit 1 (Day 1)
timeFrame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
measure: Part 2: Change From Baseline in Hematology Parameter: Red Blood Cell Count- Substance P Only at Challenge Visit 2 (Week 2)
timeFrame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
measure: Part 1: Change From Baseline in Hematology Parameter: Reticulocyte- Substance P Only at Challenge Visit 1 (Day 1)
timeFrame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
measure: Part 2: Change From Baseline in Hematology Parameter: Reticulocyte- Substance P Only at Challenge Visit 2 (Week 2)
timeFrame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
measure: Part 1: Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase and Aspartate Aminotransferase- Substance P Only at Challenge Visit 1 (Day 1)
timeFrame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
measure: Part 2: Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase and Aspartate Aminotransferase- Substance P Only at Challenge Visit 2 (Week 2)
timeFrame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
measure: Part 1: Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin and Creatinine- Substance P Only at Challenge Visit 1 (Day 1)
timeFrame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
measure: Part 2: Change From Baseline in Clinical Chemistry Parameters: Total Bilirubin and Creatinine- Substance P Only at Challenge Visit 2 (Week 2)
timeFrame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
measure: Part 1: Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN)- Substance P Only at Challenge Visit 1 (Day 1)
timeFrame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
measure: Part 2: Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, and Urea/BUN- Substance P Only at Challenge Visit 2 (Week 2)
timeFrame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
measure: Part 1: Change From Baseline in Clinical Chemistry Parameter: Total Protein- Substance P Only at Challenge Visit 1 (Day 1)
timeFrame: Baseline (Day 1: pre-dose) and At Day 1 (Visit 1)
measure: Part 2: Change From Baseline in Clinical Chemistry Parameter: Total Protein- Substance P Only at Challenge Visit 2 (Week 2)
timeFrame: Baseline (Day 1: pre-dose) and At Week 2 (Visit 2)
measure: Part 1: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 1 (Day 1)
timeFrame: At Day 1 (Visit 1)
measure: Part 2: Number of Participants With Worst Case Urinalysis Parameters Post-Baseline Relative to Baseline- Substance P Only at Challenge Visit 2 (Week 2)
timeFrame: At Week 2 (Visit 2)
measure: Part 1: Number of Participants With Clinically Significant Abnormal 12-lead Electrocardiogram (ECG) Findings- Substance P Only at Challenge Visit 1 (Day 1)
timeFrame: At Day 1 (Visit 1)
measure: Part 2: Number of Participants With Clinically Significant Abnormal 12-lead ECG Findings- Substance P Only at Challenge Visit 1 (Day 1) and Challenge Visit 2 (Week 2)
timeFrame: At Day 1 (Visit 1) and Week 2 (Visit 2)
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: GSK Investigational Site
Study officials:
References:
citation: Ten Voorde W, Akinseye C, Abdisalaam I, Wind S, Klarenbeek N, Bergmans M, van Doorn M, Rissmann R, Kaur R, Hotee S, Foster K, Nair A, Fortunato L, Macphee C, Mole S, Baumann K, Brigandi R. Intradermal substance P as a challenge agent in healthy individuals. Clin Transl Sci. 2023 Oct;16(10):1856-1865. doi: 10.1111/cts.13592. Epub 2023 Aug 7.