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

JRCT ID: jRCT2061220017

Registered date:19/05/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Pruritus
• Date of first enrollment: 20/05/2022
• Target sample size: 208
• Countries of recruitment: Argentina,Japan,Canada,Japan,Italy,Japan,Korea,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Drug: Dupilumab (SAR231893)
Pharmaceutical form: Injection solution, Route of administration: Subcutaneous
Drug: Placebo
Pharmaceutical form: Injection solution, Route of administration: Subcutaneous
Drug: Fexofenadine (loratadine if not available)
Pharmaceutical form: Tablet or capsule, Route of administration: Oral
Drug: Moisturizer
Pharmaceutical form: NA, Route of administration: Topical

Outcome(s)

Primary Outcome

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 12 [ Time Frame: Baseline to Week 12 ]
WI-NRS is a patient reported outcome (PRO) comprised of a single item rated on a scale from 0 (No itch) to 10 (Worst imaginable itch).
2. Study B: Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by >=4 from baseline to Week 12 [ Time Frame: Baseline to Week 12 ]
WI-NRS is a PRO comprised of a single item rated on a scale from 0 (No itch) to 10 (Worst imaginable itch).

Secondary Outcome

The following No.1 (22) -3 (24) are for Study A and B.
1 (22). Proportion of participants who scored "none" or "mild" in Patient Global Impression of Severity (PGIS) of pruritus at Week 12 [ Time Frame: Week 12 ]
The PGIS of pruritus is a one-item categorical scale that asks participants to provide the overall self-assessment of their pruritus severity on a 4-point scale for the past week. Response choices are: "None", "Mild", "Moderate", "Severe".
2 (23). Absolute change from baseline in weekly average of daily WI-NRS at Week 12 [ Time Frame: Baseline to Week 12 ]
WI-NRS is a PRO comprised of a single item rated on a scale from 0 (No itch) to 10 (Worst imaginable itch).
3 (24). Percent change from baseline in weekly average of daily WI-NRS at Week 12 [ Time Frame: Baseline to Week 12 ]
WI-NRS is a PRO comprised of a single item rated on a scale from 0 (No itch) to 10 (Worst imaginable itch).

The following No.4-21 are for Study A.
4. Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by >=4 from baseline to Week 24 [ Time Frame: Baseline to Week 24 ]
WI-NRS is a PRO comprised of a single item rated on a scale from 0 (No itch) to 10 (Worst imaginable itch).
5. Proportion of participants who scored "none" or "mild" in PGIS of pruritus at Week 24 [ Time Frame: Week 24 ]
The PGIS of pruritus is a one-item categorical scale that asks participants to provide the overall self-assessment of their pruritus severity on a 4-point scale for the past week. Response choices are: "None", "Mild", "Moderate", "Severe".
6. Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by >=4 from baseline over time until Week 24 [ Time Frame: Baseline to Week 24 ]
WI-NRS is a PRO comprised of a single item rated on a scale from 0 (No itch) to 10 (Worst imaginable itch).
7. Time to first response of WI-NRS >=4 points reduction from baseline by Week 24 [ Time Frame: Baseline to Week 24 ]
WI-NRS is a PRO comprised of a single item rated on a scale from 0 (No itch) to 10 (Worst imaginable itch).
8. Absolute change from baseline in weekly average of daily WI-NRS at Week 24 [ Time Frame: Baseline to Week 24 ]
WI-NRS is a PRO comprised of a single item rated on a scale from 0 (No itch) to 10 (Worst imaginable itch).
9. Percent change from baseline in weekly average of daily WI-NRS at Week 24 [ Time Frame: Baseline to Week 24 ]
WI-NRS is a PRO comprised of a single item rated on a scale from 0 (No itch) to 10 (Worst imaginable itch).
10. Absolute change from baseline in weekly average of daily sleep disturbances numerical rating scale (NRS) at Week 12 [ Time Frame: Baseline to Week 12 ]
The sleep disturbance NRS is to be used by the participants to report the degree of their sleep loss related to itch over the past 24 hours. Participants will rate their sleep disturbance from 0 (no sleep loss related to itch) to 10 (I cannot sleep at all due to itch) once daily in the morning.
11. Percent change from baseline in weekly average of daily sleep disturbances NRS at Week 12 [ Time Frame: Baseline to Week 12 ]
Refer to No.10 about the sleep disturbance NRS.
12. Change from baseline in Dermatology Life Quality Index (DLQI) score at Week 12 [ Time Frame: Baseline to Week 12 ]
The DLQI is a validated 10-item questionnaire to measure dermatology-specific quality of life (QoL) in adult patients. Overall scoring ranges from 0 to 30, with a higher score indicating a poorer QoL.
13. Change from baseline in the Itchy quality of life (ItchyQoL) score at Week 12 [ Time Frame: Baseline to Week 12 ]
ItchyQoL is a pruritus-specific QoL instrument that measures specifically disease burden in pruritus patients. It is a 22-item instrument that measures the degree to which pruritus affects quality-of-life for the past week. The overall score is the average of the 22 items ranging from 1 to 5. A higher score corresponds to a more adverse impact on QoL.
14. Change from baseline in Hospital Anxiety and Depression Scale (HADS) total score at Week 12 [ Time Frame: Baseline to Week 12 ]
The HADS is a validated questionnaire for screening anxiety and depression in non-psychiatric populations. The total score ranges from 0 to 42. 0 to 7= normal; 8 to 10= borderline abnormal; 11 to 21= abnormal.
15. Absolute change from baseline in weekly average of daily sleep disturbances NRS at Week 24 [ Time Frame: Baseline to Week 24 ]
Refer to No.10 about the sleep disturbance NRS.
16. Percent change from baseline in weekly average of daily sleep disturbances NRS at Week 24 [ Time Frame: Baseline to Week 24 ]
Refer to No.10 about the sleep disturbance NRS.
17. Change from baseline in DLQI score at Week 24 [ Time Frame: Baseline to Week 24 ]
Refer to No.12 about the DLQI.
18. Change from baseline in the ItchyQoL score at Week 24 [ Time Frame: Baseline to Week 24 ]
Refer to No.13 about ItchyQoL.
19. Change from baseline in HADS total score at Week 24 [ Time Frame: Baseline to Week 24 ]
Refer to No.14 about the HADS.
20. Percentage of participants experiencing treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) from baseline through end of study (EOS) [ Time Frame: Baseline to Week 36 ]
21. Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab [ Time Frame: Baseline to Week 36 ]

The following No.25-33 are for Study B.
25. Proportion of participants with improvement (reduction) in weekly average of daily WI-NRS by >=4 from baseline over time until Week 12 [ Time Frame: Baseline to Week 12 ]
WI-NRS is a PRO comprised of a single item rated on a scale from 0 (No itch) to 10 (Worst imaginable itch).
26. Time to first response of WI-NRS >=4 points reduction from baseline by Week 12 [ Time Frame: Baseline to Week 12 ]
WI-NRS is a PRO comprised of a single item rated on a scale from 0 (No itch) to 10 (Worst imaginable itch).
27. Absolute change from baseline in weekly average of daily sleep disturbances NRS at Week 12 [ Time Frame: Baseline to Week 12 ]
Refer to No.10 about the sleep disturbance NRS.
28. Percent change from baseline in weekly average of daily sleep disturbances NRS at Week 12 [ Time Frame: Baseline to Week 12 ]
Refer to No.10 about the sleep disturbance NRS.
29. Change from baseline in DLQI score at Week 12 [ Time Frame: Baseline to Week 12 ]
Refer to No.12 about the DLQI.
30. Change from baseline in the ItchyQoL score at Week 12 [ Time Frame: Baseline to Week 12 ]
Refer to No.13 about ItchyQoL.
31. Change from baseline in HADS total score at Week 12 [ Time Frame: Baseline to Week 12 ]
Refer to No.14 about the HADS.
32. Percentage of participants experiencing TEAEs or SAEs from baseline through EOS [ Time Frame: Baseline to Week 24 ]
33. Incidence of treatment-emergent ADA against dupilumab [ Time Frame: Baseline to Week 24 ]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 90age old
• Gender: Both

Include criteria

- 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.
- Participants with chronic pruritus for at least 6 months before the screening visit.
- 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).
- Chronic pruritus must affect at least 2 of the following body areas: legs, arms, or trunk.
- History of insufficient control of the chronic pruritus with prior treatment.
- Participants should receive optimal treatment for concomitant conditions that could impact pruritus (eg, diabetes, iron deficiency).
- 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.
- 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.
- Participants scored "severe" in the PGIS of pruritus on Day 1.

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:
- Severe concomitant illness(es) that, in the Investigator's judgment, would adversely affect the patient's participation in the study.
- 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.
- Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drug within 2 weeks before the screening visit.
- HIV infection.
- Severe renal failure (dialysis).
- Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the run-in visit.
- 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 and completely treated and resolved non metastatic squamous or basal cell carcinoma of the skin.
- History of hypersensitivity or intolerance to non-sedative antihistamines.
- Participation in prior dupilumab clinical study or have been treated with commercially available dupilumab.

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT05263206,2021-004315-76