A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Barzolvolimab in Patients with Prurigo Nodularis

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

25 Sep 2024 → ongoing

Decision date (initial)

2025-07-28

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Celldex Therapeutics

External identifiers

EU CT number

2023-510279-80-00

ClinicalTrials.gov

NCT06366750

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

"Double-Blind Main Phase (MAIN): To evaluate the clinical effect of barzolvolimab, compared to placebo, on itch response as measured by the proportion of participants with ≥ 4-point improvement in the worst intensity itch per a numeric rating scale (WI-NRS), in participants with PN
Open-label Extension Phase (OLE)
To evaluate the safety profile of barzolvolimab in participants with PN"

Secondary objectives 9

1. Main: To evaluate the clinical effect of barzolvolimab, compared to placebo on itch response as measured by the proportion of participants with ≥ 4-point improvement in WI-NRS and on change from baseline in the WI-NRS in participants with PN at different timepoints
2. Main: To evaluate the clinical effect of barzolvolimab, compared to placebo, on skin lesions as measured by the Investigator Global Assessment for chronic prurigo, in participants with PN
3. Main: To evaluate the clinical effect of barzolvolimab on PN by additional investigator assessments and patient-reported outcomes
4. Main: To evaluate the clinical effect of barzolvolimab on health-related quality of life in participants with PN
5. Main: To evaluate the safety profile the of barzolvolimab in participants with PN
6. OLE: To evaluate the clinical effect of barzolvolimab on itch response as measured by the WI-NRS in participants with PN
7. OLE: To evaluate the clinical effect of barzolvolimab on skin lesions as measured by the IGA for chronic prurigo in participants with PN.
8. OLE: To evaluate the clinical effect of barzolvolimab on PN by patient-reported outcomes in participants with PN
9. OLE: To evaluate the clinical effect of barzolvolimab on health-related quality of life in participants with PN

Conditions and MedDRA coding

Prurigo nodularis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. 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.
2. 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.
3. 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.
4. 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).
5. 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.)
6. 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.)
7. 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.)
8. 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.
9. 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.
10. 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.
11. Main 2: Male or female, ≥ 18 years of age.
12. Main 3: Has received a diagnosis of PN by a dermatologist at least 3 months prior to the Screening Visit.
13. 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
14. 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.
15. 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).
16. 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.
17. 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.
18. 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 30

1. 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).
2. 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.
3. Main 11: Planned or anticipated use of any prohibited medications during screening and throughout the study.
4. 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."
5. Main 13: History of anaphylaxis.
6. 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).
7. 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.
8. 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.
9. 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.
10. 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).
11. Main 19: Known active hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or coronavirus disease of 2019 (COVID-19) infection.
12. Main 2: PN due to medications.
13. 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.
14. Main 21: Other screening laboratory or electrocardiogram (ECG) findings that are considered clinically significant.
15. Main 22: Active infection requiring treatment with systemic antibiotics, antivirals, antifungals, antiparasitics or antiprotozoals at the Screening Visit.
16. 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.
17. 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.
18. Main 25: Prior receipt of barzolvolimab.
19. 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.
20. Main 27: Participants who live in detention on court order or on regulatory action will not be enrolled.
21. 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.
22. Main 3: Unilateral PN lesions that are limited to a small, localized area(s) on one side of the body.
23. 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.
24. 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.
25. 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)."
26. Main 7: Intralesional treatments of PN with a corticosteroid or botulin toxin within 4 weeks of the Baseline (Day 1) Visit.
27. Main 8: Phototherapy of PN with ultraviolet (UV) A or UVB within 4 weeks of the Baseline (Day 1) Visit.
28. 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."
29. OLE 1: Developed any of the exclusion criteria as described in the MAIN phase.
30. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Main: Proportion of participants with improvement (reduction) in WI-NRS by ≥ 4 from baseline to Week 12.
2. OLE: Incidence and severity of AEs from OLE baseline through Week X40.

Secondary endpoints 35

1. Main: Proportion of participants with improvement (reduction) in WI-NRS by ≥ 4 from baseline to Week 4, Week 24 and over time.
2. Main: Proportion of participants with IGA-CNPG-S score of 0 or 1 at Weeks 4. 12 and 24.
3. Main: Proportion of participants with improvement (reduction) in WI-NRS by ≥ 4 from baseline and IGA-CNPG-S score of 0 or 1 at Weeks 4, 12 and 24.
4. Main: Proportion of participants with IGA for activity of chronic prurigo (IGA-CPG-A) score of 0 or 1 at Weeks 4, 12 and 24.
5. Main: Absolute and percentage change from baseline in WI-NRS at Weeks 4, 12 and 24.
6. Main: Absolute and percentage change from baseline in Sleep Quality Numerical Rating Scale (SQ-NRS) at Weeks 4, 12 and 24.
7. Main: Absolute and percentage change from baseline in Worst Pain Numerical Rating Scale (WP-NRS) at Weeks 4, 12 and 24.
8. Main: Absolute and percentage change from baseline in PROMIS Fatigue-SF Daily at Weeks 4, 12 and 24.
9. Main: Absolute and percentage change from baseline in DLQI at Weeks 4, 12 and 24.
10. Main: Proportion of participants with WI-NRS score < 2 at Weeks 4, 12 and 24.
11. Main: Proportion of participants with improvement (reduction) in SQ-NRS by ≥ 4 from baseline to Week 4, 12 and 24.
12. Main: Proportion of participants with improvement (reduction) in WP-NRS by ≥ 4 from baseline to Weeks 4, 12 and 24.
13. Main: Proportion of participants with improvement (reduction) of ≥ 4 in DLQI from baseline to Weeks 4, 12 and 24.
14. Main: Proportion of participants achieving DLQI score of 0 or 1 at Weeks 4. 12 and 24.
15. Main: Absolute and percentage change from baseline in PGIS, and PGIS-SD at Weeks 4, 12 and 24.
16. Main: Vital signs, safety laboratory tests, physical examination findings, electrocardiograms (ECGs), and the incidence and severity of adverse events (AEs) throughout the study.
17. Main: Absolute and percentage change from baseline in IGA-CNPG-S at Weeks 4, 12, and 24.
18. Main: PGIC and PGIC-SD (also including the absolute and percentage change from Week 4) at Weeks 4, 12, and 24
19. OLE: Proportion of participants with improvement (reduction) in weekly average WI-NRS by ≥ 4 from OLE baseline through Week X24
20. OLE: Proportion of participants with IGA-CNPG-S score of 0 or 1 through Week X24
21. OLE: Proportion of participants with improvement (reduction) in weekly average WI-NRS by ≥ 4 from OLE baseline and IGA-CNPG-S score of 0 or 1 through Week X24
22. OLE: Proportion of participants with IGA-CPG-A score of 0 or 1 through Week X24
23. OLE: Absolute and percentage change in weekly average WI-NRS from OLE baseline through Week X24
24. OLE: Absolute and percentage change in IGA-CNPG-S from OLE baseline through Week X24
25. OLE: Absolute and percentage change in weekly average SQ-NRS from OLE baseline through Week X24
26. OLE: Absolute and percentage change in weekly average WP-NRS from OLE baseline through Week X24
27. OLE: Absolute and percentage change in weekly average PROMIS Fatigue-SF Daily from OLE baseline through Week X24
28. OLE: Absolute and percentage change in DLQI from OLE baseline through Week X24
29. OLE: Proportion of participants with weekly average WI-NRS score < 2 through Week X24
30. OLE: Proportion of participants with improvement (reduction) in weekly average SQ-NRS by ≥ 4 from OLE baseline through Week X24
31. OLE: Proportion of participants with improvement (reduction) in weekly average WP-NRS by ≥ 4 from OLE baseline through Week X24
32. OLE: Proportion of participants with improvement (reduction) of ≥ 4 in DLQI from OLE baseline through Week X24
33. OLE: Proportion of participants achieving DLQI score of 0 or 1 through Week X24
34. OLE: Absolute and percentage change in PGIS and PGIS-SD from OLE baseline through Week X24
35. OLE: PGIC and PGIC-SD (also including the absolute and percentage change from Week X4) at each visit through Week X24

Investigational products

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

Test 2

Placebo 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

Clinical Development

Third parties 9

Locations

4 EU/EEA countries · 31 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 33 files

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

Application history

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