Substance P Challenge in Healthy Participants

NCT04676763 | Completed Results

• 1 other identifier: 213224
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Skin Diseases

Keywords

Substance P; Wheal response; Flare response; Skin challenge

Outcome Measures

Primary Outcomes (2)

• 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)

  Wheal response-time AUC during the 2 hours post-challenge period following skin challenge for Substance P (SP) was calculated using the trapezoidal rule. The wheal response was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50, 150 and 500 picomoles (pmol) during the 2 hours post-challenge period.

  0, 5, 10, 15, 20, 40, 60, 90 and 120 minutes post-challenge on Day 1 (Visit 1)

• 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)

  Wheal response-time AUC during the 2 hours post-challenge period following skin challenge for Substance P was calculated using the trapezoidal rule. The wheal response was calculated for each control challenge (saline and histamine) and each ascending Substance P concentration: 5, 15, 50 and 150 pmol during the 2 hours post-challenge period.

  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 (44)

• 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)

  2 hours post-challenge on Day 1 (Visit 1)

• 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)

  2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge at Week 2 (Visit 2)

• 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)

  2 hours post-challenge on Day 1 (Visit 1)

• 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)

  2 hours post-challenge on Day 1 (Visit 1) and 2 hours post-challenge at Week 2 (Visit 2)

• 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)

  2 hours post-challenge on Day 1 (Visit 1)

Study Arms (2)

Substance P challenge in Part 1

EXPERIMENTAL

Eligible participants will receive control challenge with saline and histamine, followed by challenge with ascending concentrations of Substance P. Part 1 will include a single challenge visit.

Drug: Substance P; Drug: Normal Saline; Drug: Histamine

Substance P challenge in Part 2

EXPERIMENTAL

Eligible participants will receive control challenge with saline and histamine, followed by challenge with ascending concentrations of Substance P. Part 2 will include two challenge visits.

Drug: Substance P; Drug: Normal Saline; Drug: Histamine

Interventions

Substance P DRUG

Participants will receive Substance P

Substance P challenge in Part 1; Substance P challenge in Part 2

Normal Saline DRUG

Participants will receive normal saline as Negative control

Substance P challenge in Part 1; Substance P challenge in Part 2

Histamine DRUG

Participants will receive histamine as Positive control

Substance P challenge in Part 1; Substance P challenge in Part 2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Leiden, 2333 CL, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 37547990 BACKGROUND

MeSH Terms

Conditions

Skin Diseases

Interventions

Substance P; Saline Solution; Histamine

Condition Hierarchy (Ancestors)

Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Tachykinins; Kinins; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Neuropeptides; Oligopeptides; Proteins; Nerve Tissue Proteins; Autacoids; Inflammation Mediators; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Ethylamines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Reponse Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: It is an open-label study.
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parts 1 and 2 will run sequentially. Part 1 will include 1 challenge visit; Part 2 will include two challenge visits.

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: December 21, 2020
• Study Start: March 2, 2021
• Primary Completion: July 21, 2021
• Study Completion: July 21, 2021
• Last Updated: January 20, 2025
• Results First Posted: February 8, 2024

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

NL (1)