Efficacy and Safety Evaluation of Barzolvolimab in Prurigo Nodularis: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial
- Trial ID
- 2023-510279-80-00
- Protocol
- CDX0159-10
- Sponsor
- Celldex Therapeutics Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the clinical effect of **barzolvolimab**, compared to placebo, on itch response in participants with **prurigo nodularis** (PN). This is measured by the proportion of participants achieving a ≥4-point improvement in the worst intensity itch per a numeric rating scale (WI-NRS). Additionally, the study aims to assess the safety profile of barzolvolimab in these participants. The clinical relevance of this objective lies in addressing the significant symptom burden of itch in PN, which can severely impact patients' quality of life.
Secondary objectives include:
- Evaluating the clinical effect of barzolvolimab on itch response as measured by the proportion of participants with ≥4-point improvement in WI-NRS and change from baseline in WI-NRS at different timepoints.
- Assessing the effect on skin lesions using the Investigator Global Assessment for chronic prurigo.
- Evaluating additional investigator assessments and patient-reported outcomes to determine the effect on PN.
- Assessing the impact on health-related quality of life in participants with PN.
- Evaluating the safety profile of barzolvolimab in participants with PN.
- In the open-label extension phase, evaluating the clinical effect on itch response and skin lesions, as well as patient-reported outcomes and health-related quality of life.
Participants
The clinical trial involves a total of **60 participants** diagnosed with **prurigo nodularis**, a chronic skin condition characterized by intensely itchy nodules. The study population includes both male and female subjects aged **18 years and older**. Participants were selected based on their ability to provide informed consent and their willingness to comply with study requirements, including maintaining a daily study diary. The trial population is characterized by individuals who have a documented history of inadequate response to prescription topical medications or for whom such medications are medically inadvisable. Participants are required to apply a topical moisturizer regularly and maintain certain health parameters, such as normal white blood cell counts and liver enzyme levels. The study includes individuals with severe itch, defined by a numeric rating scale, and those with a significant number of nodules distributed bilaterally on the body. The trial also considers lifestyle factors, such as the use of contraception for participants of childbearing potential. The selection criteria ensure that participants have a stable health status, allowing for the evaluation of the clinical effect and safety profile of the investigational drug, barzolvolimab, compared to placebo.
Plans and Procedures
The clinical trial is a **randomized, double-blind, placebo-controlled** study designed to evaluate the efficacy and safety of **barzolvolimab** in patients with **prurigo nodularis**. The trial is structured into two phases: the Double-Blind Main Phase (MAIN) and the Open-Label Extension Phase (OLE). The MAIN phase aims to assess the clinical effect of barzolvolimab on itch response, while the OLE phase focuses on evaluating the safety profile of the drug. The trial is expected to last until July 2026, with recruitment starting in September 2024.
Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on specific inclusion criteria, such as a diagnosis of prurigo nodularis and severe itch. The MAIN phase will include regular follow-up visits to monitor the primary endpoint, which is the proportion of participants with a ≥4-point improvement in the worst intensity itch numeric rating scale (WI-NRS) by Week 12. Secondary endpoints will be assessed at Weeks 4, 12, and 24, including changes in itch severity, sleep quality, and quality of life measures.
The OLE phase will continue to monitor participants who completed the MAIN phase, with follow-up visits extending through Week 40. Participants will be evaluated for safety and efficacy, with endpoints similar to those in the MAIN phase. The end-of-study visit will conclude the trial, ensuring all data is collected and any remaining safety concerns are addressed.
Participant involvement is expected to last up to 24 weeks for the MAIN phase, with the possibility of extension into the OLE phase. Conditions that may lead to early termination from the study include non-compliance with study procedures, withdrawal of consent, or the occurrence of adverse events deemed clinically significant by the investigator. The trial will adhere to rigorous scientific and ethical standards to ensure the integrity and reliability of the data collected.
Treatment
The clinical trial involves the administration of **Barzolvolimab**, a recombinant humanized anti-KIT IgG1κ monoclonal antibody. This experimental medication is provided in two pharmaceutical forms: a **solution for injection** and a **solution for injection in pre-filled syringe**. The active substance, **Barzolvolimab**, is a protein-based therapeutic agent developed by Celldex Therapeutics, Inc. The maximum daily dose is 450 mg, with a total maximum dose of 2250 mg over a treatment period of 24 weeks. The medication is administered via **subcutaneous use**. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.
The study also includes a **placebo** control, which is the vehicle of Barzolvolimab containing 0 mg/mL of the active substance. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo is administered in the same manner as the experimental medication to provide a consistent comparison between the treatment and control groups.
Efficacy
The clinical trial aims to assess the efficacy of **Barzolvolimab** in patients with Prurigo Nodularis through a Phase 2, randomized, double-blind, placebo-controlled study. The primary endpoint for efficacy evaluation is the proportion of participants achieving a ≥ 4-point improvement in the Worst Intensity Itch Numeric Rating Scale (WI-NRS) from baseline to Week 12. Secondary endpoints include the proportion of participants with a ≥ 4-point improvement in WI-NRS at Weeks 4, 24, and over time, as well as the proportion of participants achieving an Investigator Global Assessment for Chronic Nodular Prurigo Stage (IGA-CNPG-S) score of 0 or 1 at Weeks 4, 12, and 24.
Additional secondary endpoints involve absolute and percentage changes from baseline in WI-NRS, Sleep Quality Numerical Rating Scale (SQ-NRS), Worst Pain Numerical Rating Scale (WP-NRS), and Dermatology Life Quality Index (DLQI) at Weeks 4, 12, and 24. The study will also monitor the proportion of participants with WI-NRS scores below 2 and those achieving significant improvements in SQ-NRS, WP-NRS, and DLQI. Efficacy assessments will be conducted using validated scales and patient-reported outcomes at specified timepoints throughout the study duration.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Main 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. Patients must be able to provide informed consent themselves.
- Main 6: Documented history before the Screening Visit that participant had inadequate response to prescription topical medications or that topical medications are medically inadvisable for the participant (such as concerns for safety). Inadequate response to prescription topical medications is defined as failure to achieve or maintain clear, or almost clear skin, or mild disease activity of PN lesions per IGA-CNPG-S (i.e., 0=clear, 1=almost clear, 2=mild; despite treatment with a daily topical regimen of TCS of medium to high potency (with or without a concomitant TCI or other topical antipruritic) applied for ≥ 4 weeks or for the maximum duration recommended by the product label (e.g., 2 weeks for super-potent TCS), whichever is shorter.
- Main 7: Willing to apply a topical moisturizer (emollient) once or twice a day during screening and throughout the study. Participants must have applied a stable dose of topical emollient (moisturizer) once or twice daily for at least 5 out of the 7 consecutive days immediately before Day 1.
- Main 8: White blood count (WBC), absolute neutrophil count (ANC), and platelets above the lower limit of normal (LLN) range range and hemoglobin no less than1 g/dL below the LLN, as defined by the central laboratory at screening. ( *for 8, 9 and 10 above if test results do not meet the above criteria, a repeat test may be performed to determine eligibility).
- Main 9: Aspartate aminotransferase (AST) ≤ 2X the upper limit of normal (ULN,) and total bilirubin ≤ ULN (unless elevated bilirubin is related to Gilbert’s Syndrome), at screening* (*for 8, 9, 10 and 11 above if test results do not meet the above criteria, a repeat test may be performed to determine eligibility.)
- Main 10: Alanine aminotransferase (ALT) ≤ 2 X ULN and total bilirubin ≤ ULN (unless elevated bilirubin is related to Gilbert’s Syndrome), at screening*. (*for 8, 9, 10 and 11 above if test results do not meet the above criteria, a repeat test may be performed to determine eligibility.)
- Main 11: Estimated glomerular filtration rate based on creatinine (eGFRcr) as calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation is ≥ 45 mL/min/1.73 m2, at screening*. Note: participants with renal disease may be included if this criterion is met. (*for 8, 9, 10 and 11 above if test results do not meet the above criteria, a repeat test may be performed to determine eligibility.)
- Main 12: Females must meet one of the following criteria: If of childbearing potential, agrees to use highly effective contraception from the time of the Screening Visit and for at least 150 days after receipt the final dose of study treatment. Highly effective methods of contraception include the following: • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, administered as oral, intravaginal or transdermal • progestogen-only hormonal contraception associated with inhibition of ovulation administered as oral, injectable or by implantable means • intrauterine device (IUD) • intrauterine hormone-releasing system (IUS) • tubal ligation Females of non-childbearing potential, who are surgically sterile (i.e., had undergone complete hysterectomy, bilateral salpingectomy or bilateral oophorectomy) or in a menopausal state (at least 1 year without menses), as confirmed by follicle stimulating hormone (FSH) levels, are eligible.
- Main 13: Male participants must agree to use barrier contraceptive methods with female partners of childbearing potential throughout the study and for at least 150 days after receiving the final dose of the study treatment. Additionally, these female partners must use highly effective contraception methods during the same period. Male participants who have undergone a vasectomy, confirmed as surgically successful, are exempt from this requirement. Male participants must also agree not to donate sperm during the study and for at least 150 days after receiving the study treatment. Male participants must agree to use highly effective methods of contraception with female partners of childbearing potential during the study and must also agree to not donate sperm during the study and for at least 150 days after receipt of the study treatment.
- Main 14: Willing and able to comply with all study requirements and procedures. Participants must comply with daily study diary completion for at least 5 of the 7 days for the 7-day period immediately preceding randomization.
- Main 2: Male or female, ≥ 18 years of age.
- Main 3: Has received a diagnosis of PN by a dermatologist at least 3 months prior to the Screening Visit.
- Main 4: A total of at least 20 PN nodules with bilateral distribution on both arms and/or both legs and/or both sides of the trunk at screening and Day 1 (i.e., Investigator Global Assessment for stage of chronic nodular prurigo (IGA-CNPG-S) score ≥ 3
- Main 5: 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 the Baseline (Day 1) Visit. Note: participant must have daily diary data for at least 5 of these 7 days to determine eligibility.
- OLE 1: Participated in the MAIN phase, did not discontinue the MAIN Treatment Period early, and completed through at least the MAIN EOT Visit (Week 24).
- OLE 2: Has active PN defined as mean daily WI-NRS ≥ 7 and IGA-CNPG-S ≥ 3 at Week 24 or at any of the follow-up visits between Week 24 and Week 40 of the MAIN phase.
- OLE 3: Treatment-related adverse events (AEs) in the MAIN phase must have resolved, returned to normal or baseline, or are no longer considered clinically significant by the investigator.
- OLE 4: Must continue to meet eligibility criteria as described for the MAIN phase and remain a candidate for treatment in the clinical judgment of the treating investigator.
Exclusion Criteria
- Main 1: PN due to neuropathy (e.g., small fiber neuropathy, post-herpetic itch, notalgia paresthetica, brachioradial pruritus) or psychiatric disorders (e.g., delusional parasitosis, factitious dermatitis, obsessive-compulsive disorders, schizophrenia).
- Main 10: Biologic therapy including approved or investigational agents (e.g., dupilumab, investigational monoclonal antibodies against IL-31 or IL-31 receptor or other monoclonal antibody) within 3 months or 5 half-lives, whichever is longer, prior to the Baseline (Day 1) Visit.
- Main 11: Planned or anticipated use of any prohibited medications during screening and throughout the study.
- Main 12: Receipt of a live vaccine within 2 months prior to the Baseline (Day 1) Visit (participants must agree to avoid live vaccination during study treatment and within 4 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."
- Main 13: History of anaphylaxis.
- Main 14: Any known contraindications or hypersensitivity to any component of study treatments and drugs of similar chemical classes (i.e., murine, chimeric or human antibodies).
- Main 15: Women who are pregnant or nursing. All female participants with reproductive potential must have a negative pregnancy test prior to starting study treatment.
- Main 16: 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.
- Main 17: Participants with moderate-to-severe pulmonary or cardiovascular diseases; see Appendix 7 for guidelines. Note: participants with symptomatic cardiovascular or pulmonary disease that requires medication should be carefully assessed and discussed with the medical monitor to ensure their cardiovascular and/or pulmonary status does not increase their risk of study participation.
- Main 18: Participants 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 pharmacodynamic actions of epinephrine (e.g., beta blockers).
- Main 19: Known active hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or coronavirus disease of 2019 (COVID-19) infection.
- Main 2: PN due to medications.
- Main 20: Malignancy or a history of malignancy (Exception: fully treated skin basal cell carcinoma, non-metastatic squamous cell carcinomas, or cervical intraepithelial neoplasia, or cervical carcinoma in situ with no evidence of recurrence) within five (5) years prior to Screening Visit.
- Main 21: Other screening laboratory or electrocardiogram (ECG) findings that are considered clinically significant.
- Main 22: Active infection requiring treatment with systemic antibiotics, antivirals, antifungals, antiparasitics or antiprotozoals at the Screening Visit.
- Main 23: 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 participant inappropriate for entry into the study.
- Main 24: 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.
- Main 25: Prior receipt of barzolvolimab.
- Main 26: Participation in another research study involving an investigational product within 3 months or 5 half-lives, whichever is greater, prior to the Baseline (Day 1) Visit.
- Main 27: Participants who live in detention on court order or on regulatory action will not be enrolled.
- Main 28: 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.
- Main 3: Unilateral PN lesions that are limited to a small, localized area(s) on one side of the body.
- Main 4: Active unstable (e.g., in an acute flare) pruritic skin conditions in addition to PN (e.g., moderate to severe atopic dermatitis) that would interfere with the assessment of PN based on the investigator’s clinical judgment.
- Main 5: Participants with documented moderate to severe atopic dermatitis (e.g., an Investigator Global Assessment [IGA] for atopic dermatitis score of 3 or 4, an Eczema Area and Severity Index [EASI] score of ≥16, or a scoring atopic dermatitis [SCORAD] score of ≥25) within 6 months before the start of screening.
- Main 6: The following topical treatments for PN within 2 weeks of the Baseline (Day 1) Visit: • TCS/TCI • Initiation of treatment with prescription moisturizers or moisturizers containing additives such as ceramide, hyaluronic acid, urea, menthol, polidocanol, or filaggrin degradation products during screening Note: Participants who initiated such moisturizers before screening can continue using them as long as the dose remains stable throughout the study. • Topical JAK-1 inhibitors • Topical capsaicin • Topical vitamin D analogs (e.g., calcipotriol) • Topical phosphodiesterase 4 (PDE4) inhibitors (e.g., crisaborole) • Topical cannabinoids • Topical anaesthetics (lidocaine, prilocaine, polidocanol, amitriptyline hydrochloride/ketamine mixture, pramoxine) • Topical mast cell stabilizers (e.g., cromolyn, ketotifen) • Topical products containing other itch relieving agents (e.g., menthol, strontium)."
- Main 7: Intralesional treatments of PN with a corticosteroid or botulin toxin within 4 weeks of the Baseline (Day 1) Visit.
- Main 8: Phototherapy of PN with ultraviolet (UV) A or UVB within 4 weeks of the Baseline (Day 1) Visit.
- Main 9: Non-biologic systemic (oral or injectable) agents listed below, including investigational agents, within 4 weeks or 5 half-lives, whichever is longer, prior to the Baseline (Day 1) Visit. Note: Non-biologic systemic (oral or injectable) treatments: first-generation sedating antihistamines, opioid receptor modulators (e.g., naltrexone, naloxone, nalbuphine), cannabinoids, mast cell stabilizers (e.g., cromolyn, ketotifen), neurokinin receptor-1 antagonists (e.g., aprepitant), retinoids, immunosuppressants/Confidential Page 15 of 86 immunomodulators (e.g., corticosteroids, methotrexate, cyclosporin, tacrolimus, mycophenolate mofetil, azathioprine, Janus kinase [Jak] inhibitors, thalidomide, lenalidomide), or other approved systemic agents with anti-pruritic effects."
- OLE 1: Developed any of the exclusion criteria as described in the MAIN phase.
- OLE 2: Participants who, during their participation in the MAIN phase, experienced an AE, which in the opinion of the investigator could indicate that continued treatment with barzolvolimab may present an unreasonable risk for the participant.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Croatia | Not Recruiting | 06 Sept 2024 | 12 |
 Germany | Not Recruiting | 06 Sept 2024 | 27 |
 Poland | Not Recruiting | 06 Sept 2024 | 25 |
 Spain | Not Recruiting | 06 Sept 2024 | 14 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
BARZOLVOLIMAB | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 450 | 24 | PRD11544482 |
Placebo for this study is the barzolvolimab vehicle (containing 0 mg/mL barzolvolimab). | Placebo | N/A | — | — | — | N/A |
BARZOLVOLIMAB | Test | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS USE | 450 | 24 | PRD11655867 |