This study is being conducted to determine the safety and tolerability of ruxolitinib 1.5% cream under maximal use conditions in participants with Prurigo Nodularis (PN).

Inclusion Criteria:

• Clinical diagnosis of PN ≥ 3 months before screening.
• Pruriginous lesions (defined as papules, nodules, plaques, umbilicated lesions, and linear lesions) on ≥ 2 different body areas (such as right and left leg) at screening and baseline.
• Total estimated treatment BSA ≥ 25% (excluding the scalp) at screening and baseline.
• IGA-CPG-S score of ≥ 2 at screening and baseline.
• Baseline PN-related WI-NRS score ≥ 7. Baseline WI-NRS score is defined as the 7-day average of WI-NRS scores before Day 1 (data from a minimum of 4 out of 7 days prior to Day 1 is needed).

Exclusion Criteria:

• Chronic or acute pruritus due to a condition other than PN.
• Active AD lesions (signs and symptoms other than dry skin) within 6 months of screening and baseline.
• Acute or chronic active HBV or HCV infection.
• Any underlying condition known to be associated with the clinical presentation of PN that is not under control (stable) prior to the baseline visit.
• Any serious illness or medical, physical, or psychiatric condition(s) that, in the investigator's opinion, would interfere with full participation in the study, including administration of study cream and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.

Other protocol-defined Inclusion/Exclusion Criteria may apply.