Efficacy and safety of subcutaneous dupilumab for the treatment of adult participants with chronic pruritus of unknown origin (CPUO)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

28 Apr 2022 → ongoing

Decision date (initial)

2025-11-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Sanofi-Aventis Research & Development

External identifiers

EU CT number

2023-508879-36-00

EudraCT number

2021-004315-76

WHO UTN

U1111-1253-9888

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

Study A and B:
• To demonstrate the efficacy of dupilumab on itch response in participants with CPUO

Secondary objectives 4

1. To demonstrate the efficacy of dupilumab on additional itch endpoints in participants with CPUO
2. To demonstrate the improvement in sleep, anxiety and depression, and health-related quality of life (HRQoL)
3. To evaluate safety outcome measures
4. To evaluate immunogenicity of dupilumab

Conditions and MedDRA coding

Pruritus

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001501-PIP11-21

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of the trial participants. Further details on Sanofi´s data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Participant must be 18 (or the legal age of consent in the jurisdiction in which the study is taking place) to 90 years of age inclusive, at the time of signing the informed consent.
2. Participants with chronic pruritus for at least 6 months before the screening visit.
3. Chronic pruritus considered of unknown origin as assessed by the investigator at baseline (excluding chronic pruritus secondary to dermatological or systemic conditions, of neuropathic or psychogenic origin or secondary to drugs).
4. Chronic pruritus must affect at least 2 of the following body areas: legs, arms, or trunk.
5. History of insufficient control of the chronic pruritus with prior treatment.
6. Participants should receive optimal treatment for concomitant conditions that could impact pruritus (eg, diabetes, iron deficiency).
7. Participants must have a history of severe itch and a worst itch score of ≥7 at screening on the WI-NRS (score scale ranges from 0 to 10; higher score indicates worse itch) and Patient global impression of severity (PGIS) of pruritus scored “severe” at screening.
8. Participants must have an average worst itch score of ≥7 in the 7 days prior to run-in visit and in the 7 days prior to Day 1 on the WI-NRS.
9. Participants scored “severe” in the PGIS of pruritus on Day 1.

Exclusion criteria 10

1. Severe concomitant illness(es) that, in the Investigator’s judgment, would adversely affect the patient’s participation in the study.
2. Patients with active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis, unless it is well documented by a specialist that the participant has been adequately treated and can now start treatment with a biologic agent.
3. Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drug within 2 weeks before the screening visit.
4. HIV infection.
5. Severe renal failure (dialysis).
6. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the run-in visit
7. Known or suspected immunodeficiency.
8. Active malignancy or history of malignancy within 5 years before the baseline visit, except completely treated in situ carcinoma of the cervix and completely treated and resolved non metastatic squamous or basal cell carcinoma of the skin.
9. History of hypersensitivity or intolerance to non-sedative antihistamines.
10. Participation in prior dupilumab clinical study or have been treated with commercially available dupilumab.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Study A: Proportion of participants with improvement (reduction) in weekly average of daily worst-itch numerical rating scale (WI-NRS) by ≥4 from baseline to Week 24
2. Study B: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline to Week 12

Secondary endpoints 41

1. Study A: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline to Week 12
2. Study A: Proportion of participants who scored “none” or “mild” in Patient Global Impression of Severity (PGIS) of pruritus at Week 24
3. Study A; Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline over time until Week 24
4. Study A: Time to first response of WI-NRS ≥4 points reduction from baseline by Week 24
5. Study A: Absolute change from baseline in weekly average of daily WI-NRS at Week 24
6. Study A: Percent change from baseline in weekly average of daily WI-NRS at Week 24
7. Study A: Proportion of participants who scored “none” or “mild” in PGIS of pruritus at Week 12
8. Study A: Absolute change from baseline in weekly average of daily WI-NRS at Week 12
9. Study A: Percent change from baseline in weekly average of daily WI-NRS at Week 12
10. Study A: Absolute change from baseline in weekly average of daily sleep disturbances numerical rating scale (NRS) at Week 24
11. Study A: Percent change from baseline in weekly average of daily sleep disturbances NRS at Week 24
12. Study A: Change from baseline in Dermatology Life Quality Index (DLQI) score at Week 24
13. Study A: Change from baseline in the Itchy quality of life (ItchyQoL) score at Week 24
14. Study A: Change from baseline in Hospital Anxiety and Depression Scale (HADS) total score at Week 24
15. Study A: Absolute change from baseline in weekly average of daily sleep disturbances NRS at Week 12
16. Study A: Percent change from baseline in weekly average of daily sleep disturbances NRS at Week 12
17. Study A: Change from baseline in DLQI score at Week 12
18. Study A: Change from baseline in the ItchyQoL score at Week 12
19. Study A: Change from baseline in HADS total score at Week 12
20. Study A: Percentage of participants experiencing treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) from baseline through end of study (EOS)
21. Study A: Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab
22. Study B: Proportion of participants who scored “none” or “mild” in PGIS of pruritus at Week 24
23. Study B: Proportion of participants who scored “none” or “mild” in PGIS of pruritus at Week 12
24. Study B: Absolute change from baseline in weekly average of daily WI-NRS at Week 12
25. Study B: Percent change from baseline in weekly average of daily WI-NRS at Week 12
26. Study B: Absolute change from baseline in weekly average of daily WI-NRS at Week 24
27. Study B: Percentage change from baseline in weekly average of daily WI-NRS at Week 24
28. Study B: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline, sustained from Week 19 through Week 24
29. Study B: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥5 from baseline to Week 24
30. Study B: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥4 from baseline to Week 24
31. Study B: Proportion of participants with weekly average of daily WI-NRS <2 at Week 24
32. Study B: Time to first response of WI-NRS ≥4 points reduction from baseline by Week 24
33. Study B: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by ≥5 from baseline to Week 12
34. Study B: Proportion of participants with weekly average of daily WI-NRS <2 at Week 12
35. Study B: Absolute change from baseline in weekly average of daily itch-related sleep disturbance NRS at Week 12 and Week 24
36. Study B: Percent change from baseline in weekly average of daily itch-related sleep disturbance NRS at Week 12 and Week 24
37. Study B: Change from baseline in DLQI score at Week 12 and Week 24
38. Study B: Change from baseline in the ItchyQoL score at Week 12 and Week 24
39. Study B: Change from baseline in HADS total score at Week 12 and Week 24
40. Study B: Percentage of participants experiencing TEAEs or SAEs from baseline through EOS
41. Study B: Incidence of treatment-emergent ADA against dupilumab

Investigational products

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

Test 1

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 15

Locations

6 EU/EEA countries · 32 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 103 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