A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Dose ranging Study to Assess the Efficacy and Safety of CDX 0159 in Patients with Chronic Inducible Urticaria

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Celldex Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

9 Nov 2022 → 13 Sep 2025

Decision date (initial)

2024-11-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Celldex Therapeutics Inc.

External identifiers

EU CT number

2024-516988-87-00

EudraCT number

2021-006447-95

ClinicalTrials.gov

NCT05405660

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Dose response, Efficacy, Pharmacodynamic

To evaluate efficacy of different dose regimens of CDX-0159 compared to placebo, in achieving a negative provocation test in patients with H1AH refractory CIndU in each subtype (ColdU and SD).

Secondary objectives 3

1. To evaluate efficacy of different dose regimens of CDX-0159 compared to placebo, in improving provocation thresholds and itch triggered by provocation test in each CIndU subtype
2. To evaluate efficacy of different dose regimens of CDX-0159 compared to placebo, in achieving a negative provocation test and improving itch triggered by provocation test in combined CIndU patients
3. To evaluate the safety profile of different dose regimens of CDX-0159 compared to placebo, in each CIndU subtype, and combined CIndU patients.

Conditions and MedDRA coding

Chronic Inducible Urticaria

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Read, understood, and provided written informed consent, and Health Insurance Portability and Accountability Act (HIPAA) authorization if applicable, after the nature of the study has been fully explained.
2. 2. Male or female, ≥ 18 years of age at the time of signing the informed consent
3. 3. Diagnosis of ColdU or SD for ≥ 3 months prior to Screening Visit 1
4. 4. Patients with chronic ColdU or SD whose urticaria remains uncontrolled despite a stable regimen of a second-generation non-sedating H1AH as defined by all of the following: Recurrent pruritic wheals with or without angioedema due to ColdU or SD for ≥ 6 weeks prior to Screening Visit 1 despite treatment with a H1AH Patients must have been on a stable regimen of daily use of a single second-generation non-sedating H1AH at approved or increased (up to 4 times the approved) dose for the treatment of ColdU or SD for ≥ 4 weeks prior to randomization and which is expected to remain stable at the time of randomization and throughout the study UCT < 12 at Screening Visit 1 and the randomization visit (Visit 3)
5. 5. Provocation tests that meet the following criteria: For ColdU patients: developing a wheal at the provocation site within 10 min after provocation using TempTest® at any temperature at both screening (Visit 1) and randomization (Visit 3) For SD patients, developing a wheal at the provocation site within 10 min after provocation using FricTest® with ≥ 3 pins at both screening (Visit 1) and randomization (Visit 3)
6. 6. Hemoglobin, white blood count (WBC), absolute neutrophil count (ANC), and platelets must be > the lower limit of normal (LLN) and < 1.5 X the upper limit of normal (ULN) range if the higher values between ULN and 1.5 X ULN are deemed to be not clinically significant by the Investigator, at Screening Visits 1 and 2*
7. 7. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2 x ULN, and total bilirubin < ULN (unless elevated bilirubin is related to Gilbert’s Syndrome), at Screening Visits 1 and 2*
8. 8. Females must meet one of the following criteria: (X) Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, administered as oral, intravaginal or transdermal (X) progestogen-only hormonal contraception associated with inhibition of ovulation administered as oral, injectable or by implantable means (X) Intrauterine device (IUD) (X) Intrauterine hormone-releasing system (IUS) Females of non-childbearing potential, who are surgically sterile (i.e., had undergone complete hysterectomy, salpingectomy and bilateral oophorectomy) or in a menopausal state (at least 1 year without menses), as confirmed by FSH levels, are eligible.
9. 9. Male patients must agree that while participating in the study and for at least 150 days after receipt of the study treatment, they will use highly effective methods of contraception with female partners of childbearing potential, and they will not donate sperm. Vasectomy is considered as a highly effective method of contraception provided that the vasectomized patient has received medical assessment confirming the surgical success.
10. Willing and able to comply with all study requirements and procedures, including the completion of a daily diary during screening and throughout the study. Note: For study eligibility, patients need to complete the diary for at least 6 of the 7 days immediately prior to randomization.

Exclusion criteria 26

1. 1. Diseases with possible symptoms of urticaria or angioedema such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), autoimmune syndromes with urticarial lesions (e.g., Schnitzler Syndrome) and hereditary or acquired angioedema (e.g., due to C1 inhibitor deficiency).
2. 2. Active chronic spontaneous urticaria (CSU) or other forms of CIndU including cholinergic-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, or contact-urticaria that would confound assessments of ColdU or SD, respectively, based on the investigator’s clinical judgment.
3. 3. Familial cold urticaria (FCU), also known as familial cold autoinflammatory syndrome (FCAS).
4. 4. Any other active pruritic skin diseases that would confound CIndU assessments (e.g., atopic dermatitis, psoriasis, bullous pemphigoid, dermatitis herpetiformis, prurigo nodularis, chronic pruritus of unknown origin) based on the investigator's clinical judgment
5. 5. Regular (3 or more days a week) use of topical corticosteroid, topical calcineurin inhibitors or topical antihistamines, first-generation sedating antihistamines (e.g., diphenhydramine, hydroxyzine, doxylamine) and other sedatives/hypnotics (e.g., doxepin), within 1 week of Screening Visit 1.
6. 6. Phototherapy with ultraviolet (UV) A or UVB within 4 weeks of Screening Visit 1.
7. 7. Non-biologic systemic (oral or injectable) agents listed below, including investigational agents, within 4 weeks or 5 half-lives, whichever is longer, prior to Screening Visit 1. Note: Non-biologic systemic (oral or injectable) agents: corticosteroids, non-steroidal immunosuppressants (e.g., methotrexate, cyclosporin, tacrolimus, mycophenolate mofetil, azathioprine, cyclophosphamide), and other immunomodulators (e.g., dapsone, sulfasalazine, hydroxychloroquine, and colchicine, Jak inhibitors, Bruton's kinase [BTK] inhibitors), mast cell stabilizers (e.g., cromolyn, ketotifen), anabolic steroid (e.g., danazol), and other investigational agents; and trigger desensitization protocol
8. 8. Biologic therapy including investigational agents (e.g., omalizumab, ligelizumab, dupilumab, IL-1 inhibitor, interferon gamma, TNF inhibitor, B-cell depleting therapy (e.g., rituximab), or other investigational monoclonal antibodies) within 3 months prior to Screening Visit 1.
9. 9. Trigger desensitization within 4 weeks of Screening Visit 1.
10. 10. Planned or anticipated use of any prohibited medications during screening and study treatment, and follow-up
11. 11. Receipt of a live vaccine within 2 months prior to the Baseline (Day 1) Visit (patients must agree to avoid live vaccination during study treatment and within 3 months thereafter). Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally inactivated virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. Currently authorized COVID-19 vaccines are allowed.
12. 12. Diagnosis of idiopathic anaphylaxis or exercise-induced anaphylaxis, or a history of anaphylaxis (such as those due to Hymenoptera venom or IgE-mediated food allergy), that in the opinion of the investigator, would increase the patient’s risk for systemic hypersensitivity reactions; or any known contraindications or hypersensitivity to any component of study treatments, drugs of similar chemical classes (i.e., to murine, chimeric, or human antibodies) or antihistamines. Note: ColdU patients with a history of cold-induced anaphylaxis due to cold exposure over a large body surface area (such as swimming in cold water) are not excluded
13. 13. Women who are pregnant or nursing. All female patients with reproductive potential must have a negative pregnancy test prior to starting study treatment.
14. 14. Severe or uncontrolled chronic diseases (e.g., chronic hepatic or renal disease, diabetes mellitus) that might interfere with the evaluation of the clinical effect or safety of study treatment.
15. 15. Patients with moderate-to-severe pulmonary or cardiovascular diseases, see Appendix 23 for guidelines. Note: patients with symptomatic cardiovascular or pulmonary disease that requires medication should be carefully assessed and discussed with the medical monitor to assure their cardiovascular and/or pulmonary status does not increase their risk of study participation.
16. 16. Patients with contraindications for use of epinephrine (e.g., history of closed angle glaucoma, significant arrhythmias, myocardial infarction, or cardiomyopathy) or are taking medications that might interfere with the pharmacodynamic actions of epinephrine (e.g., beta blockers)
17. 17. Known active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
18. 18. Patients with active COVID-19 infection.
19. 19. History of malignancy within 5 years before Screening Visit 1, except fully treated carcinoma in situ of the cervix, full treated and resolved non-metastatic squamous or basal cell carcinoma of the skin.
20. 20. Other screening laboratory or electrocardiogram (ECG) findings that are considered clinically significant.
21. 21. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antifungals, antiparasitics or antiprotozoals during the Screening period.
22. 22. Any other acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with study participation or could interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into the study.
23. 23. Procedures requiring general or epidural anaesthesia within 8 weeks prior to study treatment, minor procedures (e.g., dental) within 14 days prior to study treatment, or anticipation of procedures requiring general anaesthesia during study participation.
24. 24. Prior receipt of CDX-0159
25. 25. Patients who live in detention on court order or on regulatory action will not be enrolled.
26. 26. Sponsor or contract research organization (CRO) staff directly involved in the conduct of the study, and site staff supervised by the investigator, and their respective family members.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Proportion (%) of patients with a negative provocation test at Week 12 in the ColdU subtype cohort (X) For ColdU patients, a negative provocation test is defined as absence of wheals at the provocation site within 10 min at ≤ 4°C after provocation using TempTest®
2. Proportion (%) of patients with a negative provocation test at Week 12 in the SD subtype cohort (X) For SD patients, a negative provocation test is defined as absence of wheals at the provocation site within 10 min at 0 pins after provocation using the FricTest®

Secondary endpoints 7

1. Mean change from baseline to Week 12 in CTT in the ColdU subtype cohort
2. Mean change from baseline to Week 12 in CFT in the SD subtype cohort
3. Mean change from baseline to Week 12 in WI-NRSprovo in the ColdU subtype cohort
4. Mean change from baseline to Week 12 in WI-NRSprovo in the SD subtype cohort
5. Proportion (%) of patients with a negative provocation test at Week 12 in the combined CIndU subtype cohorts
6. Mean change from baseline to Week 12 in WI-NRSprovo in the combined CIndU subtype cohorts
7. Proportion (%) of patients experiencing TEAEs over the 20-week treatment period by subtype cohort and in the combined CIndU subtype cohorts

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Celldex Therapeutics Inc.

Sponsor organisation

Celldex Therapeutics Inc.

Address

53 Frontage Road Suite 220

City

Hampton

Postcode

08827-4034

Country

United States

Scientific contact point

Organisation

Celldex Therapeutics Inc.

Contact name

Science Department

Public contact point

Organisation

Celldex Therapeutics Inc.

Contact name

Science Department

Locations

7 EU/EEA countries · 34 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 52 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications