A Single Dose Study of the Safety, Pharmacokinetics and Pharmacodynamics of CDX-0159 in Patients With Cold Contact Urticaria, Symptomatic Dermographism, or Cholinergic Urticaria

An Open Label, Phase 1 Single Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of CDX-0159 as Add on Therapy in Patients With Cold Contact Urticaria, Symptomatic Dermographism and Cholinergic Urticaria

This is a study to determine the safety of CDX-0159 in patients with Cold Contact Urticaria, Symptomatic Dermographism, or Cholinergic Urticaria.

Study Overview

• Status: Completed
• Conditions: Cold Urticaria; Symptomatic Dermographism; Cholinergic Urticaria; Cold Contact Urticaria; Symptomatic Dermatographism
• Intervention / Treatment: Drug: CDX-0159

Detailed Description

This study is an open label Phase 1 study evaluating the safety, pharmacokinetics, and pharmacodynamics of a single dose of CDX-0159 in patients with Cold Contact Urticaria, Symptomatic Dermographism, or Cholinergic Urticaria who remain symptomatic despite treatment with antihistamines. Twenty patients with Cold Contact Urticaria, ten patients with Symptomatic Dermographism, and ten patients with Cholinergic Urticaria will be enrolled in four separate cohorts for a total of 40 patients.

Prospective patients will be screened with tests in clinic as well as daily at home diaries for 2 weeks prior to enrollment. CDX-0159 will be administered intravenously on Day 1. Post-treatment, patients will be followed for 12 weeks with an optional longer term follow up period.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charité University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Diagnosis of Cold Contact Urticaria, Symptomatic Dermographism, or Cholinergic Urticaria which does not respond to antihistamines

   • Diagnosis for ≥ 3 months; symptoms of both hive (wheal) and itch/burning/painful sensation despite concurrent use of anti-histamines
   • During screening, in clinic, for Cold Contact Urticaria, patients must have a positive cold stimulation test, for Symptomatic Dermographism, patients must have a positive FricTest®, and for Cholinergic Urticaria, patients must have a positive pulse-controlled ergometry (PCE) provocation test
   • On stable dose of antihistamines
2. Other than a diagnosis of Cold Contact Urticaria, Symptomatic Dermographism, or Cholinergic Urticaria, no other conditions which would introduce additional risk factors or would interfere with the study procedures, as determined by the investigator, based on a medical evaluation
3. Female and male patients must use highly effective contraception from the time of the screening visit and for at least 150 days after receipt of study treatment
4. Willing and able to comply with all study requirements and procedures including completion of a daily medication diary and questionnaires

Key Exclusion Criteria:

1. A clearly defined diagnosis of hives or angioedema other than chronic urticaria.
2. Receipt of prior biologic therapy (e.g.: omalizumab, dupilumab, ligelizumab) within past 3 months
3. Treatment with immunosuppressives (e.g. systemic corticosteroids, cyclosporine, methotrexate, dapsone, cyclophosphamide, tacrolimus and mycophenolate mofetil, hydroxychloroquine or others) within 4 weeks or 5 half lives
4. Active COVID-19 infection
5. HIV, hepatitis B or hepatitis C infection

There are additional criteria that your study doctor will review with you to confirm you are eligible for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CDX-0159; 20 patients with Cold Contact Urticaria, 10 patients with Symptomatic Dermographism, and 10 patients with Cholinergic Urticaria will be enrolled and treated with a single dose of CDX-0159	Drug: CDX-0159; Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as assessed by the incidence and severity of adverse events	Safety of a single dose of CDX-0159 as determined by adverse events	From Day 1 through week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
For patients with Cold Contact Urticaria, Change in Critical Temperature Thresholds (CTT)	The change from baseline in critical temperature thresholds over time as determined by provocation testing using the TempTest®	From Day 1 to Day 85
For patients with Symptomatic Dermographism, change in provocation thresholds	The change from baseline in provocation thresholds over time as determined by provocation testing using the FricTest®	From Day 1 to Day 85
For patients with Cholinergic Urticaria, changes in baseline Urticaria Activity Score Provocation (UASprovo)	Changes from baseline and percentage of responders as measured by UASprovo	From Day 1 to Day 85
Changes from baseline in Urticaria Control Test (UCT)	Changes from baseline and percentage of responders for the UCT and modified UCT	From Day 1 to Day 85
Blood Biomarkers	Pre-treatment and post-treatment blood samples will be collected and analyzed for changes in Stem Cell Factor	From Day 1 to Day 85
Blood Biomarkers	Pre-treatment and post-treatment blood samples will be collected and analyzed for changes in tryptase	From Day 1 to Day 85
Pharmacokinetic Evaluation	CDX-0159 concentrations will be measured.	From Day 1 to Day 85
Immunogenicity Evaluation	Patients will be monitored for the development of anti-drug antibodies.	From Day 1 to Day 85

Collaborators and Investigators

• Sponsor: Celldex Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2020
• Primary Completion (Actual): December 16, 2022
• Study Completion (Actual): May 12, 2023

Study Registration Dates

• First Submitted: September 8, 2020
• First Submitted That Met QC Criteria: September 8, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Actual): May 17, 2023
• Last Update Submitted That Met QC Criteria: May 16, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Skin Diseases, Vascular; Hypersensitivity; Urticaria
• Other Study ID Numbers: CDX0159-03; 2020-002792-35 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No