Efficacy and Safety of Rocatinlimab in Adults with Prurigo Nodularis Unresponsive to Topical Therapies: A Phase 3, Randomized, Double-blind, Placebo-controlled Study

The primary objective is to assess the efficacy of multiple dose levels of rocatinlimab versus placebo on the patient‑reported outcome (PRO) measure of pruritus in adults with Prurigo Nodularis who are inadequately controlled with or ineligible for topical therapy, thereby determining the therapeutic impact on the most burdensome symptom of the disease. Secondary objectives include:

• Evaluation of dose‑dependent efficacy versus placebo using the investigator’s clinical assessment of disease severity.
• Confirmation of efficacy on the PRO measure of pruritus, mirroring the primary endpoint.
• Assessment of dose‑dependent effects on the PRO measure of skin pain associated with the disease.
• Combined analysis of PRO‑reported pruritus and investigator‑rated disease activity.
• Characterization of the safety profile and tolerability of rocatinlimab in the study population.

The trial enrolled 277 participants who were adults (≥ 18 years of age) of both sexes and had a confirmed clinical diagnosis of Prurigo Nodularis present for at least three months, characterized by chronic pruritus for more than six weeks, ongoing scratching behavior, and a minimum of 20 pruriginous nodules distributed bilaterally on the limbs, trunk, or both. Selection required informed consent, a documented inadequate response to topical therapy (or contraindication to such therapy), and, when applicable, prior systemic treatment or phototherapy followed by appropriate wash‑out periods. Eligible individuals also needed to have completed at least four of seven days of daily electronic itch diary entries before randomization. General health status was required to be stable, with no concurrent conditions that would confound evaluation of the investigational product. No specific dietary or physical‑activity restrictions were imposed as part of eligibility.

The study is a randomized, double-blind, placebo-controlled Phase 3 trial evaluating subcutaneous rocatinlimab versus placebo in adult subjects with Prurigo Nodularis who are inadequately controlled on topical therapies. After obtaining informed consent, participants undergo a screening visit to confirm eligibility criteria, including disease duration, lesion count, and diary‑recorded itch scores, followed by a prerandomization baseline assessment on Day 1. Subjects are then allocated to treatment arms and receive study drug at the specified dose every 4 weeks for a total of 52 weeks. Scheduled follow‑up visits occur at Weeks 4, 12, 24, 36, and 48 to evaluate efficacy endpoints, safety parameters, and tolerability, with the primary endpoint being reduction in weekly average daily itch score at predefined time points. An end‑of‑study visit at Week 52 (or early withdrawal) completes the trial assessments, including final investigator lesion evaluation, quality‑of‑life questionnaires, and collection of adverse‑event data. Participant involvement therefore extends from screening through the 52‑week treatment period and a final follow‑up, totaling approximately 54 weeks. Early termination may occur due to serious adverse events, emergence of contraindicating medical conditions, non‑compliance with study procedures, or participant withdrawal of consent.

The investigational product Rocatinlimab is supplied as a solution for injection intended for subcutaneous administration. Each dose contains 9999 mg per millilitre and is administered according to the dosing schedule defined in the study protocol. The pharmaceutical form is a sterile solution prepared for injection, and the route of administration is subcutaneous injection.

The comparator arm utilizes a matching Placebo formulation, designated for AMG 451, which contains no active pharmaceutical ingredient. The placebo is administered by the same subcutaneous route and follows an identical dosing schedule to maintain blinding.

Both study treatments are delivered in a double‑blind fashion, with dosing performed at study visits as specified in the protocol. Compliance with the administration schedule is monitored through site documentation of each injection, verification of returned study material, and, when applicable, electronic adherence records. The trial enrolls adult subjects with Prurigo Nodularis who are inadequately controlled by, or not eligible for, topical therapies.

Efficacy will be assessed by measuring the reduction from baseline in the weekly average of the daily itching score using a patient‑reported outcome (PRO) measure of pruritus at pre‑specified time points throughout the 52‑week treatment period.

Additional efficacy parameters include investigator assessment of Prurigo Nodularis lesions, changes from baseline in daily itching, daily skin pain, quality of life, and sleep disturbance. These secondary endpoints will be captured at baseline and at each scheduled study visit during the trial.

Data collection will utilize daily electronic diaries for itch and pain scores, a standardized investigator rating scale for lesion evaluation, and validated questionnaires for quality of life and sleep disruption. Analyses will compare the magnitude of change from baseline between rocatinlimab dose groups and placebo at the defined assessment time points.