A Study to Evaluate Efficacy, Safety and Tolerability of Remibrutinib in Adult Participants With Severe Chronic Pruritus of Unknown Origin (CPUO)

A 52-week Multi-center, Randomized, Double-blind, Placebo Controlled Phase 3 Study to Evaluate the Efficacy, Safety and Tolerability of Remibrutinib in Adult Participants With Severe Chronic Pruritus of Unknown Origin (CPUO)

The purpose of this phase 3 study is to establish the efficacy, safety and tolerability of remibrutinib in adult participants with severe chronic pruritus of unknown origin (CPUO).

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Pruritus of Unknown Origin
• Intervention / Treatment: Drug: Placebo; Drug: Remibrutinib

Detailed Description

This is a global, phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy, safety, and tolerability of remibrutinib in adult participants with severe CPUO.

The design includes 4 periods, for a total duration of up to 60 weeks:

• Screening period: up to 4 weeks.
• Double-blind treatment period (treatment period 1, TP1): 24 weeks of double-blind treatment with remibrutinib or matching placebo
• Open-label treatment period (treatment period 2, TP2): 28 weeks of open-label treatment with remibrutinib. The participants randomized to the placebo arm will be switched to remibrutinib at Week 24.
• Safety follow-up period: 4 weeks of treatment-free safety follow-up.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Participant must be ≥ 18 years of age, at the time of signing the informed consent.
• Participants with chronic pruritus for at least 4 months prior to screening.
• Chronic pruritus considered of unknown origin as assessed by the investigator at baseline (e.g., excluding chronic pruritus related to primary dermatological or systemic conditions, neuropathic or psychogenic origin or secondary to drugs or other allergen exposures).
• Chronic pruritus must affect at least 2 of the following body areas: trunk, arms, or legs (cannot be unilateral and/or dermatomal in distribution).
• Participants with ongoing, severe chronic pruritus despite the use of emollients and who are candidates for systemic therapy.
• Participants must have severe itch defined by a WI-NRS ≥7 at screening; score scale ranges from 0 to 10; higher score indicates worse itch.
• Participants must have an average WI-NRS ≥7 over the 7 days prior to randomization/baseline visit.
• The average WI-NRS score over the preceding 7 days prior to the randomization/baseline visit will be calculated based on the daily WI-NRS scores (0-10).
• Participants must have PGIS of pruritus scored as 3 "severe" at screening and baseline visits.

Key Exclusion Criteria:

• Any active skin conditions (e.g., atopic dermatitis, psoriasis, etc.) that may interfere with the assessment of CPUO.
• Known systemic condition(s) or medication(s) that are considered by the investigator to be the primary cause of current pruritus.
• Known or suspected infectious disease that is active, chronic or recurrent which precludes the participant from participating in the clinical trial as per Investigator´s assessment. These infectious diseases include but are not limited to opportunistic infections (e.g., tuberculosis, atypical mycobacterioses, listeriosis or aspergillosis) and/or known or suspected HIV infection.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• Significant bleeding risk or coagulation disorders. History of gastrointestinal bleeding, e.g., in association with use of nonsteroidal anti-inflammatory drugs (NSAIDs), that was clinically relevant (e.g., where intervention was indicated or requiring hospitalization or blood transfusion). Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited.
• History or current hepatic disease, including but not limited to, acute or chronic hepatitis, cirrhosis or hepatic failure or aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) levels of more than 1.5 x upper limit of normal (ULN) or International Normalized Ratio (INR) of more than 1.5 at screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remibrutinib; Remibrutinib film coated tablets	Drug: Remibrutinib; Oral administration of remibrutinib; Other Names: LOU064
Experimental: Placebo followed by remibrutinib; Matching placebo. At the Week 24 visit, all participants will receive active treatment (remibrutinib).	Drug: Placebo; Oral administration of matching placebo.; Drug: Remibrutinib; Oral administration of remibrutinib; Other Names: LOU064

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants achieving ≥4 point reduction from baseline in Worst itch Numerical Rating Scale (WI NRS)	The WI-NRS is a patient-reported outcome (PRO) instrument consisting of a single question that asks participants to rate the severity of their worst itch over a defined period. The score range is from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicate worse itch severity.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants achieving ≥4 point reduction from baseline in WI NRS	The WI-NRS is a PRO instrument consisting of a single question that asks participants to rate the severity of their worst itch over a defined period. The score range is from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicate worse itch severity.	Baseline, Week 4
Proportion of participants achieving Patient Global Impression of Severity (PGIS) score of 0 (none) or 1 (mild)	The PGIS of pruritus is a PRO measure consisting of a single item that captures the participant's overall self-assessment of the severity of their pruritus (itch) over a defined recall period. The score range is from 0 (none) to 3 (severe). Lower scores indicate better outcome.	Week 12
Proportion of participants achieving Patient Global Impression of Severity (PGIS) score of 0 (none) or 1 (mild)	The PGIS of pruritus is a PRO measure consisting of a single item that captures the participant's overall self-assessment of the severity of their pruritus (itch) over a defined recall period. The score range is from 0 (none) to 3 (severe). Lower scores indicate better outcome.	Week 24
Change from baseline in Pruritus-related Sleep Disturbance Numerical Rating Scale (SD-NRS)	The SD-NRS is a PRO instrument used to assess the degree of sleep disturbance caused by pruritus (itch). The score range is from 0 (No sleep disturbance) to 10 (Worst possible sleep disturbance). Higher scores indicate greater sleep disturbance due to pruritus.	Week 12
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Number of participants with AEs and SAEs.	Up to Week 52

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): August 14, 2026
• Primary Completion (Estimated): December 19, 2029
• Study Completion (Estimated): April 15, 2030

Study Registration Dates

• First Submitted: July 7, 2026
• First Submitted That Met QC Criteria: July 7, 2026
• First Posted (Actual): July 13, 2026

Study Record Updates

• Last Update Posted (Actual): July 13, 2026
• Last Update Submitted That Met QC Criteria: July 7, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: BTK inhibitor; chronic pruritus; remibrutinib; chronic pruritus of unknown origin; CPUO
• Additional Relevant MeSH Terms: remibrutinib
• Other Study ID Numbers: CLOU064R12301; 2025-524497-41 (Other Identifier: EU CTIS number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No