A Study of Barzolvolimab in Patients With Prurigo Nodularis

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Barzolvolimab (CDX-0159) in Patients With Prurigo Nodularis

The purpose of this study is to assess the efficacy and safety of barzolvolimab in adults with prurigo nodularis.

Study Overview

• Status: Recruiting
• Conditions: Prurigo Nodularis
• Intervention / Treatment: Biological: barzolvolimab; Other: Matching Placebo

Detailed Description

The purpose of this study is to assess the efficacy and safety of bazolvolimab (CDX-0159) in adults with prurigo nodularis.

There is a screening period of approximately 28 days, a 24-week double-blind treatment period and a 16-week follow-up period after treatment. Participants will be randomly assigned on a 1:1:1 ratio to receive barzolvolimab (CDX-0159) by subcutaneous injections of 150 mg every 4 weeks (Q4W) after an initial loading dose of 450 mg, 300 mg Q4W after an initial loading dose of 450 mg, or placebo Q4W.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Celldex Therapeutics; Phone Number: 844-723-9363; Email: info@celldex.com

Study Locations

• United States
  • Michigan
    • Troy, Michigan, United States, 48084
      • Recruiting
      • Revival Research Institute, LLC
      • Contact: Sikar Grewal; Email: grewal@rev-research.com
  • Texas
    • Webster, Texas, United States, 77598
      • Recruiting
      • Center For Clinical Studies
      • Contact: Perla Rivas; Email: privas@ccstexas.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Males and females, ≥18 years of age.

2. Diagnosis of Prurigo Nodularis by a dermatologist at least 3 months prior to Screening with:

   1. At least 20 PN nodules with bilateral distribution on both arms and/or both legs and/or both sides of the trunk at screening.
   2. An Investigators Global Assessment for stage of chronic nodular prurigo (IGA-CNPG-S) score for PN ≥ 3 at screening and Baseline (Day 1).
3. Severe itch, defined as the mean of the daily worst itch NRS (WI-NRS) score of ≥ 7 during the 7-day period immediately prior to initiation of study treatment.
4. Documented history of inadequate response to prescription topical medications or for whom topical medications are medically inadvisable.
5. Willing to apply a topical moisturizer (emollient) once or twice a day throughout the study.
6. Both males and females of child-bearing potential must agree to use highly effective contraceptives during the study and for 150 days afterwards after treatment.
7. Willing and able to complete a daily symptom electronic diary for the duration of the study and adhere to the study visit schedule.

Key Exclusion Criteria

1. PN due to neuropathy, psychiatric disorders or medications.
2. Unilateral PN lesions limited to small area on one side of the body (e.g., only one arm affected).
3. Active unstable pruritic skin conditions in addition to PN.
4. Documented atopic dermatitis (moderate to severe) within 6 months before the start of screening.
5. Females who are pregnant or nursing.
6. Known hepatitis B or hepatitis C infection or active COVID-19 infection.
7. Vaccination with a live vaccine within 2 months prior to study drug administration (subjects must agree to avoid vaccination during the study and for four months thereafter). NOTE: Inactivated vaccines are allowed such as seasonal influenza for injection. COVID-19 vaccination is allowed.
8. History of anaphylaxis.
9. Prior receipt of barzolvolimab

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: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Barzolvolimab 450 mg, then 150 mg Q4W; 450 mg subcutaneous administration loading dose on Day 1 followed by 150 mg subcutaneous administration every 4 weeks, starting on Week 4, to Week 24.	Biological: barzolvolimab; subcutaneous administration
Experimental: Barzolvolimab 450 mg, then 300 mg Q4W; 450 mg subcutaneous administration loading dose on Day 1 followed by 300 mg subcutaneous administration every 4 weeks, starting on Week 4, to Week 24.	Biological: barzolvolimab; subcutaneous administration
Placebo Comparator: Placebo; Matching placebo subcutaneous administration every 4 weeks, starting on Week 4, to Week 24.	Other: Matching Placebo; subcutaneous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with improvement in Worst Itch Numeric Rating Scale (WI-NRS) by ≥ 4 from baseline to Week 12.	WI-NRS is a validated measure of itch severity. Participants are asked daily to rate the intensity of their worst pruritis (itch) over the past 24 hours using an 11-point scale ranging from 0= no itch to 10= worst imaginable itch. Higher scores indicate more severity.	From Day 1 (first dose) to Day 85 (week 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with improvement in WI-NRS by ≥ 4 from baseline to Week 4.	WI-NRS is a validated measure of itch severity. Participants are asked daily to rate the intensity of their worst pruritis (itch) over the past 24 hours using an 11-point scale ranging from 0= no itch to 10= worst imaginable itch. Higher scores indicate more severity.	From Day 1 (first dose) to Week 4
Proportion of participants with improvement in WI-NRS by ≥ 4 from baseline to Week 24.	WI-NRS is a validated measure of itch severity. Participants are asked daily to rate the intensity of their worst pruritis (itch) over the past 24 hours using an 11-point scale ranging from 0= no itch to 10= worst imaginable itch. Higher scores indicate more severity.	From Day 1 (first dose) to Week 24
Proportion of participants with improvement in WI-NRS by ≥ 4 from baseline to Day 169 (week 24).	WI-NRS is a validated measure of itch severity. Participants are asked daily to rate the intensity of their worst pruritis (itch) over the past 24 hours using an 11-point scale ranging from 0= no itch to 10= worst imaginable itch. Higher scores indicate more severity.	From Day 1 (first dose) to Day 169 (week 24)
Proportion of participants with Investigator Global Assessment for stage of chronic nodular prurigo score (IGA-CNPG-S) of 0 or 1 at Weeks 4, 12 and 24.	The IGA-CNPG-S is an instrument used to assess the overall number of PN lesions at a given timepoint, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4 where 0= clear, 1= almost clear, 2= mild, 3= moderate, and 4= severe. Higher scores indicate severe PN. In this outcome measure, percentage of participants with an IGA-CNPG-S score of either 0 or 1 at Weeks 4, 12 and 24 will be reported.	From Day 1 (first dose) to Day 169 (week 24)
Proportion of participants with improvement in both WI-NRS by ≥ 4 from baseline and IGA-CNPG-S score of 0 or 1 at Weeks 4, 12 and 24.	WI-NRS is a validated measure of itch severity. Participants are asked daily to rate the intensity of their worst pruritis (itch) over the past 24 hours using an 11-point scale ranging from 0 = no itch to 10 =worst imaginable itch. Higher scores indicate more severity. The Investigator Global Assessment for stage of chronic nodular prurigo (IGA-CNPG-S) is an instrument used to assess the overall number of PN lesions at a given timepoint, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4 where 0= clear, 1= almost clear, 2= mild, 3= moderate, and 4= severe. Higher scores indicate severe PN. Percentage of participants who achieve both an improvement in WI-NRS and an improvement in IGA-CNPG-S will be reported in this outcome.	From Day 1 (first dose) to Day 169 (week 24)
Proportion of participants with Investigator Global Assessment for activity of chronic prurigo (IGA-CPG-A) score of 0 or 1 at Weeks 4, 12 and 24.	The IGA-CPG-A is an instrument used to assess the overall activity of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0-4 where 0= clear (0% lesions showing excoriations/crusts), 1= almost clear (1-10% lesions showing excoriations/crusts), 2= Mild (11-25% lesions showing excoriations/crusts), 3= moderate (26-75% lesions showing excoriations/crusts), 4= severe (76-100% lesions showing excoriations/crusts). Higher scores indicate severe PN. In this outcome measure, percentage of participants with an IGA-CPG-A score of either 0 (clear) or 1 (almost clear) at Weeks 4,12 and 24 will be reported.	From Day 1 (first dose) to Day 169 (week 24)
Absolute change from baseline in WI-NRS at Weeks 4, 12 and 24.	WI-NRS is a validated measure of itch severity. Participants are asked daily to rate the intensity of their worst pruritis (itch) over the past 24 hours using an 11-point scale ranging from 0= no itch to 10= worst imaginable itch. Higher scores indicate more severity.	From Day 1 (first dose) to Day 169 (week 24)
Percentage change from baseline in WI-NRS at Weeks 4, 12 and 24.	WI-NRS is a validated measure of itch severity. Participants are asked daily to rate the intensity of their worst pruritis (itch) over the past 24 hours using an 11-point scale ranging from 0= no itch to 10= worst imaginable itch. Higher scores indicate more severity.	From Day 1 (first dose) to Day 169 (week 24)
Absolute change from baseline in Sleep Quality Numerical Rating Scale (SQ-NRS) at Weeks 4, 12 and 24.	SQ-NRS is an assessment where participants rate their sleep during the past 24 hours as a score ranging from 0= best possible sleep to 10= worst possible sleep. Higher scores indicate more severity.	From Day 1 (first dose) to Day 169 (week 24)
Percentage change from baseline in SQ-NRS at Weeks 4, 12 and 24.	SQ-NRS is an assessment where participants rate their sleep during the past 24 hours as a score ranging from 0= best possible sleep to 10= worst possible sleep. Higher scores indicate more severity.	From Day 1 (first dose) to Day 169 (week 24)
Absolute change from baseline in Worst Pain Numerical Rating Scale (WP-NRS) at Weeks 4, 12 and 24.	WP-NRS is used to measure skin pain intensity. Participants are asked to rate their worst pain during the past 24 hours as a score ranging from 0= no pain to 10= worst imaginable pain. Higher scores indicate more severity.	From Day 1 (first dose) to Day 169 (week 24)
Percentage change from baseline in WP-NRS at Weeks 4, 12 and 24.	Worst Pain Numerical Rating Scale (WP-NRS) is used to measure skin pain intensity. Participants are asked to rate their worst pain during the past 24 hours as a score ranging from 0= no pain to 10= worst imaginable pain. Higher scores indicate more severity.	From Day 1 (first dose) to Day 169 (week 24)
Absolute change from baseline in Patient-Reported Outcomes Measurement Information System Fatigue - Short Form 7b Daily (PROMIS Fatigue-SF Daily) at Weeks 4, 12 and 24.	PROMIS Fatigue-SF Daily is an assessment where participants rate their fatigue on a daily basis by responding to 7 questions. Each question is based on a 5-point scale ranging from 1= never to 5= always.	From Day 1 (first dose) to Day 169 (week 24)
Percentage change from baseline in PROMIS Fatigue-SF Daily at Weeks 4, 12 and 24.	Patient-Reported Outcomes Measurement Information System Fatigue - Short Form 7b Daily (PROMIS Fatigue-SF Daily) is an assessment where participants rate their fatigue on a daily basis by responding to 7 questions. Each question is based on a 5-point scale ranging from 1= never to 5= always.	From Day 1 (first dose) to Day 169 (week 24)
Absolute change from baseline in Dermatology Life Quality Index (DLQI) at Weeks 4, 12 and 24.	The DLQI is a self-administered, dermatology-specific quality of life (QoL) questionnaire that consists of 10 questions concerning participants' perception of the impact of their skin disease on different aspects of their QoL (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment) over the previous week. The DLQI score ranges from 0= no effect on the participant's life to 30= extremely large effect on the participant's life.	From Day 1 (first dose) to Day 169 (week 24)
Percentage change from baseline in Dermatology Life Quality Index (DLQI) at Weeks 4, 12 and 24.	The DLQI is a self-administered, dermatology-specific quality of life (QoL) questionnaire that consists of 10 questions concerning participants' perception of the impact of their skin disease on different aspects of their QoL (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment) over the previous week. The DLQI score ranges from 0= no effect on the participant's life to 30= extremely large effect on the participant's life.	From Day 1 (first dose) to Day 169 (week 24)
Proportion of participants with WI-NRS score < 2 at Weeks 4, 12 and 24.	WI-NRS is a validated measure of itch severity. Participants are asked daily to rate the intensity of their worst pruritis (itch) over the past 24 hours using an 11-point scale ranging from 0 = no itch to 10 = worst imaginable itch. Higher scores indicate more severity. In this outcome measure, the proportion of participants with an improvement (reduction) in WI-NRS to a score of < 2 at Weeks 4, 12 and 24, will be reported.	From Day 1 (first dose) to Day 169 (week 24)
Proportion of participants with improvement in SQ-NRS by ≥ 4 from baseline to Week 4, 12 and 24.	Sleep Quality Numerical Rating Scale (SQ-NRS) is an assessment where participants rate their sleep during the past 24 hours as a score ranging from 0 = best possible sleep to 10 = worst possible sleep. Higher scores indicate more severity.	From Day 1 (first dose) to Day 169 (week 24)
Proportion of participants with improvement in WP-NRS by ≥ 4 from baseline to Weeks 4, 12 and 24.	Worst Pain Numerical Rating Scale (WP-NRS) is used to measure skin pain intensity. Participants are asked to rate their worst pain during the past 24 hours as a score ranging from 0 = no pain to 10 = worst imaginable pain. Higher scores indicate more severity.	From Day 1 (first dose) to Day 169 (week 24)
Proportion of participants with improvement of ≥ 4 in DLQI from baseline to Weeks 4, 12 and 24.	The DLQI is a self-administered, dermatology-specific quality of life (QoL) questionnaire that consists of 10 questions concerning participants' perception of the impact of their skin disease on different aspects of their QoL (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment) over the previous week. The DLQI score ranges from 0= no effect on the participant's life to 30= extremely large effect on the participant's life. Proportion of participants with improvement in DLQI scores of ≥ 4 points from baseline to Weeks 4,12 and 24 will be reported.	From Day 1 (first dose) to Day 169 (week 24)
Proportion of participants achieving DLQI score of 0 or 1 at Weeks 4, 12 and 24.	The DLQI is a self-administered, dermatology-specific quality of life (QoL) questionnaire that consists of 10 questions concerning participants' perception of the impact of their skin disease on different aspects of their QoL (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment) over the previous week. The DLQI score ranges from 0= no effect on the participant's life to 30= extremely large effect on the participant's life. Proportion of participants achieving DLQI scores of 0 or 1 at Weeks 4,12 and 24 will be reported.	From Day 1 (first dose) to Day 169 (week 24)
Absolute change from baseline in PGIS, PGIS-SD, PGIC and PGIC-SD.	Patient Global Impression of Severity of Disease (PGIS) is an assessment where participants rate the severity in their PN. Patient Global Impression of Severity of Sleep Disturbance (PGIS-SD) is an assessment where participants rate the severity of their sleep disturbance. PGIS and PGIS-SD are gauged on a scale ranging from 0= none to 4= very severe. Patient Global Impression of Change of Disease (PGIC) is an assessment where participants rate the change in their PN. Patient Global Impression of Change of Sleep Disturbance (PGIC-SD) is an assessment where the participants rate the change in their sleep disturbance. PGIC and PGIC-SD are gauged on a scale of 1= Much better to 5= Much worse. Participants will be asked to provide this rating in comparison to just before the participant starts taking study treatment.	From Day 1 (first dose) to Day 169 (week 24)
Percentage change from baseline in PGIS, PGIS-SD, PGIC and PGIC-SD at Weeks 4, 12 and 24.	PGIS is an assessment where participants rate the change in their PN. PGIS-SD is an assessment where participants rate the severity of their sleep disturbance. PGIS and PGIS-SD are gauged on a scale ranging from 0= none to 4= very severe. PGIC is an assessment where participants rate the change of their PN. PGIC-SD is an assessment where the participants rate the change in their sleep disturbance. PGIC and PGIC-SD are gauged on a scale of 1= Much better to 5= Much worse. Participants will be asked to provide this rating in comparison to just before the participant starts taking study treatment.	From Day 1 (first dose) to Day 169 (week 24)
Number of participants with Treatment-Emergent Adverse Events (TEAEs) throughout the study.	An adverse event (AE) is any untoward medical occurrence in a participant administered study treatment and does not have to have a causal relationship with the treatment. TEAEs are defined as AEs that develop, worsen or become serious during the treatment- emergent (TE) period from the first investigational medicinal product (IMP) administration to the last IMP administration.	From Day 1 (first dose) to Day 281 (last follow-up visit)

Collaborators and Investigators

• Sponsor: Celldex Therapeutics

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: March 27, 2024
• First Submitted That Met QC Criteria: April 15, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: CDX-0159; barzolvolimab; PN
• Additional Relevant MeSH Terms: Skin Diseases; Dermatitis; Skin Diseases, Eczematous; Prurigo; Neurodermatitis
• Other Study ID Numbers: CDX0159-10; 2023-510279-80-00 (Other Identifier: EU CT)

Drug and device information, study documents

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