Study of Dupilumab for the Treatment of Patients With Prurigo Nodularis, Inadequately Controlled on Topical Prescription Therapies or When Those Therapies Are Not Advisable (PRIME2)

NCT04202679 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: EFC164602019-003801-90U1111-1241-8174
• Study Type: interventional
• Target: 160
• Locations: 11 countries
• Sites: 57

Brief Summary

Primary Objective: To demonstrate the efficacy of dupilumab on itch response in participants with prurigo nodularis (PN), inadequately controlled on topical prescription therapy or when those therapies are not advisable. Secondary Objectives: To demonstrate the efficacy of dupilumab on additional itch endpoints in participants with PN, inadequately controlled on topical prescription therapy or when those therapies are not advisable. To demonstrate efficacy of dupilumab on skin lesions of PN. To demonstrate the improvement in health-related quality of life. To evaluate safety outcome measures. To evaluate immunogenicity of dupilumab.

Conditions

Neurodermatitis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Greater Than or Equal to (>=) 4 Points Improvement (Reduction) From Baseline in Worst-Itch Numeric Rating Scale (WI-NRS) Scores at Week 12

  WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants with \>=4 points improvement (reduction) from baseline in WI-NRS scores at Week 12 is reported in this outcome measure.

  Baseline, Week 12

Secondary Outcomes (22)

• Percentage of Participants With >=4 Points Improvement (Reduction) From Baseline in WI-NRS Scores at Week 24

  Baseline, Week 24

• Percentage of Participants With Investigator's Global Assessment For Prurigo Nodularis-Stage (IGA PN-S) Scores of 0 or 1 at Week 24

  At Week 24

• Percentage of Participants With Both an Improvement (Reduction) in WI-NRS by >=4 Points and an IGA PN-S Score of 0 or 1 From Baseline at Week 24

  Baseline, Week 24

• Percentage of Participants With IGA PN-S Scores of 0 or 1 at Week 12

  At Week 12

• Percent Change From Baseline in WI-NRS Scores at Week 24

  Baseline, Week 24

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants received placebo matched to dupilumab 600 milligrams (mg) (loading dose), subcutaneously (SC) on Day 1 followed by placebo matched to dupilumab 300 mg once every 2 weeks (q2w) for 24 weeks added to background therapy of topical corticosteroids/topical calcineurin inhibitors (TCS/TCI) at stable dose.

Drug: Placebo; Drug: Moisturizers; Drug: Low to medium potent topical corticosteroids; Drug: Topical calcineurin inhibitors

Dupilumab 300 mg Q2W

EXPERIMENTAL

Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose.

Drug: Dupilumab SAR231893; Drug: Moisturizers; Drug: Low to medium potent topical corticosteroids; Drug: Topical calcineurin inhibitors

Interventions

Dupilumab SAR231893 DRUG

Pharmaceutical form:Injection solution Route of administration: Subcutaneous

Dupilumab 300 mg Q2W

Placebo DRUG

Pharmaceutical form:Injection solution Route of administration: Subcutaneous

Placebo

Moisturizers DRUG

Pharmaceutical form: Route of administration: Topical

Dupilumab 300 mg Q2W; Placebo

Low to medium potent topical corticosteroids DRUG

Pharmaceutical form: Route of administration: Topical

Dupilumab 300 mg Q2W; Placebo

Topical calcineurin inhibitors DRUG

Pharmaceutical form: Route of administration: Topical

Dupilumab 300 mg Q2W; Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be 18 to 80 years of age, at the time of signing the informed consent.
• With a clinical diagnosis of PN defined by all of the following:
• Diagnosed by a dermatologist for at least 3 months before the Screening visit.
• On the Worst Itch Numeric Rating Scale (WI-NRS) ranging from 0 to 10, participants must have an average worst itch score of \>=7 in the 7 days prior to Day1.
• Participants must have a minimum of 20 PN lesions in total on both legs, and/or both arms and/or trunk, at Screening visit and Day 1
• History of failing a 2-week course of medium-to-superpotent topical corticosteroids (TCS) or when TCS are not medically advisable
• 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.
• Must be willing and able to complete a daily symptom eDiary for the duration of the study.

You may not qualify if:

• Participants were excluded from the study if any of the following criteria apply:
• Presence of skin morbidities other than PN and mild atopic dermatitis that may interfere with the assessment of the study outcomes.
• PN secondary to medications.
• PN secondary to medical conditions such as neuropathy or psychiatric disease.
• Within 6 months before the screening visit, or documented diagnosis of moderate to severe atopic dermatitis from screening visit to randomization visit.
• Severe concomitant illness(es) under poor control that, in the investigator's judgment, would adversely affect the participant's participation in the study.
• Severe renal conditions (eg, participants with uremia and/or on dialysis).
• Participants with uncontrolled thyroid disease.
• Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated.
• Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection, unless clinical and (if necessary) laboratory assessment have ruled out active infection before randomization.
• Active chronic or acute infection (except HIV) requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the screening visit and during the screening period.
• Known or suspected immunodeficiency.
• Active malignancy or history of malignancy within 5 years before the Baseline visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin.
• The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (57)

Investigational Site Number :8400054

Fort Smith, Arkansas, 72916, United States

Location

Investigational Site Number :8400008

Sacramento, California, 95816, United States

Location

Investigational Site Number :8400005

Pembroke Pines, Florida, 33028, United States

Location

Investigational Site Number :8400002

Plainfield, Indiana, 46168, United States

Location

Investigational Site Number :8400003

Baltimore, Maryland, 21205, United States

Location

Investigational Site Number :8400006

East Windsor, New Jersey, 08520, United States

Location

Investigational Site Number :8400001

Sugar Land, Texas, 77479, United States

Location

Investigational Site Number :1240002

Calgary, Alberta, T2G 1B1, Canada

Location

Investigational Site Number :1240006

Surrey, British Columbia, V3R 6A7, Canada

Location

Investigational Site Number :1240007

Markham, Ontario, L3P 1X3, Canada

Location

Investigational Site Number :1240008

Newmarket, Ontario, L3Y 5G8, Canada

Location

Investigational Site Number :1240001

Toronto, Ontario, M5A 3R6, Canada

Location

Investigational Site Number :1240009

Saskatoon, Saskatchewan, S7K 0H6, Canada

Location

Investigational Site Number :1520005

Valdivia, Los Ríos Region, 5110683, Chile

Location

Investigational Site Number :1520006

Osorno, Reg Metropolitana de Santiago, 5311523, Chile

Location

Investigational Site Number :1520003

Santiago, Reg Metropolitana de Santiago, 7580206, Chile

Location

Investigational Site Number :1520001

Santiago, Reg Metropolitana de Santiago, 7640881, Chile

Location

Investigational Site Number :1520004

Santiago, Reg Metropolitana de Santiago, 80004005, Chile

Location

Investigational Site Number :1520002

Santiago, Chile

Location

Investigational Site Number :2500007

Bordeaux, 33075, France

Location

Investigational Site Number :2500001

Brest, 29200, France

Location

Investigational Site Number :2500008

Le Mans, 72037, France

Location

Investigational Site Number :2500002

Lille, 59037, France

Location

Investigational Site Number :2500006

Lyon, 69003, France

Location

Investigational Site Number :2500004

Paris, 75010, France

Location

Investigational Site Number :2500005

Reims, 51100, France

Location

Investigational Site Number :2500003

Toulouse, 31059, France

Location

Investigational Site Number :3480004

Debrecen, 4032, Hungary

Location

Investigational Site Number :3480002

Orosháza, 5900, Hungary

Location

Investigational Site Number :3480005

Pécs, 7632, Hungary

Location

Investigational Site Number :3480003

Szeged, 6720, Hungary

Location

Investigational Site Number :3800001

Rozzano, Milano, 20089, Italy

Location

Investigational Site Number :3800004

Ancona, 60032, Italy

Location

Investigational Site Number :3800003

Catanzaro, 88100, Italy

Location

Investigational Site Number :3800002

Milan, 20122, Italy

Location

Investigational Site Number :6200001

Coimbra, 3000-075, Portugal

Location

Investigational Site Number :6200002

Lisbon, 1998-018, Portugal

Location

Investigational Site Number :6200003

Porto, 4099-001, Portugal

Location

Investigational Site Number :4100002

Busan, Busan, 49241, South Korea

Location

Investigational Site Number :4100003

Bucheon-si, Gyeonggi-do, 14584, South Korea

Location

Investigational Site Number :4100007

Incheon, Incheon-gwangyeoksi, 21431, South Korea

Location

Investigational Site Number :4100005

Seoul, Seoul-teukbyeolsi, 03722, South Korea

Location

Investigational Site Number :4100001

Seoul, Seoul-teukbyeolsi, 06973, South Korea

Location

Investigational Site Number :4100006

Seoul, Seoul-teukbyeolsi, 07441, South Korea

Location

Investigational Site Number :7240009

Badalona, Barcelona [Barcelona], 08916, Spain

Location

Investigational Site Number :7240001

Pontevedra, Galicia [Galicia], 36071, Spain

Location

Investigational Site Number :7240008

Santullano, Principality of Asturias, 33619, Spain

Location

Investigational Site Number :7240004

Córdoba, 14004, Spain

Location

Investigational Site Number :7240007

Madrid, 28034, Spain

Location

Investigational Site Number :7240003

Valencia, 46026, Spain

Location

Investigational Site Number :7240002

Zaragoza, 50009, Spain

Location

Investigational Site Number :1580005

Hsinchu, 30059, Taiwan

Location

Investigational Site Number :1580006

Kaohsiung City, 833, Taiwan

Location

Investigational Site Number :1580008

Taichung, Taiwan

Location

Investigational Site Number :1580001

Taipei, 10002, Taiwan

Location

Investigational Site Number :1580002

Taipei, 10449, Taiwan

Location

Investigational Site Number :8260001

Redhill, Surrey, RH1 5RH, United Kingdom

Location

Related Publications (4)

• Yosipovitch G, Kim BS, Koo JY, Chen Z, Wiggins S, Zahn J, Sugerman P, Haddad EB, Cyr SL. Dupilumab Reduces Pruritus in Clinically Distinct Dermatologic Diseases: Data from Clinical Trials on Atopic Dermatitis, Prurigo Nodularis, and Chronic Spontaneous Urticaria. Dermatol Ther (Heidelb). 2025 Nov 22. doi: 10.1007/s13555-025-01596-8. Online ahead of print.

  PMID: 41272364 DERIVED

• Kim BS, Goncalo M, Ugajin T, Gao XH, Praestgaard AH, Makhija M, Zahn J, Bansal A, Wiggins S. Efficacy and Safety of Dupilumab in Adults with Prurigo Nodularis with or Without Atopic Comorbidities: A Subgroup Analysis from Two Randomized Phase III Clinical Trials. Am J Clin Dermatol. 2026 Jan;27(1):167-180. doi: 10.1007/s40257-025-00993-1. Epub 2025 Nov 11.

  PMID: 41219577 DERIVED

• Kwatra SG, Yosipovitch G, Kim B, Stander S, Rhoten S, Ivanescu C, Haeusler N, Brookes E, Msihid J, Makhija M, Bansal A, Thomas RB, Bahloul D. Worst Itch Numeric Rating Scale for Prurigo Nodularis: A Secondary Analysis of 2 Randomized Clinical Trials. JAMA Dermatol. 2024 Aug 1;160(8):813-821. doi: 10.1001/jamadermatol.2024.1634.

  PMID: 38865146 DERIVED

• Yosipovitch G, Mollanazar N, Stander S, Kwatra SG, Kim BS, Laws E, Mannent LP, Amin N, Akinlade B, Staudinger HW, Patel N, Yancopoulos GD, Weinreich DM, Wang S, Shi G, Bansal A, O'Malley JT. Dupilumab in patients with prurigo nodularis: two randomized, double-blind, placebo-controlled phase 3 trials. Nat Med. 2023 May;29(5):1180-1190. doi: 10.1038/s41591-023-02320-9. Epub 2023 May 4.

  PMID: 37142763 DERIVED

Related Links

• EFC16460 Plain Language Results Summary

MeSH Terms

Conditions

Neurodermatitis

Interventions

dupilumab; Calcineurin Inhibitors

Condition Hierarchy (Ancestors)

Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2019
• First Posted: December 17, 2019
• Study Start: January 16, 2020
• Primary Completion: August 30, 2021
• Study Completion: November 22, 2021
• Last Updated: September 17, 2025
• Results First Posted: September 28, 2022

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

CL (6); ES (7); PT (3); CA (6); KR (6); FR (8); IT (4); TW (5); GB (1); US (7); HU (4)