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Introduction <p>Despite recent advancements in treating severe alopecia areata (AA), many patients do not achieve target efficacy with approved therapies. Ritlecitinib is an oral Janus kinase 3 (JAK3)/tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinase inhibitor approved to treat severe AA at a dose of 50-mg once daily (QD). A new phase 3 clinical trial (NCT06873945) described herein evaluates a higher dose of ritlecitinib (100-mg QD) in patients with AA. The study employs an innovative design using patient-level data from patients with similar baseline characteristics from previous AA ritlecitinib studies to form an external placebo control group, a synthetic placebo control group (extrapolating for outcomes over a longer timeframe than captured previously), and an external ritlecitinib 50-mg nonresponders group, eliminating the need to randomize patients to placebo.</p> Methods <p>This randomized, double-blind clinical trial investigates the efficacy and safety of ritlecitinib in patients aged ≥ 12&#xa0;years with AA and ≥ 50% scalp hair loss. Patients are randomized to ritlecitinib 100-mg or 50-mg QD. Those randomized to ritlecitinib 100-mg continue the 100-mg dose through week&#xa0;48. Patients randomized to ritlecitinib 50-mg with a Severity of Alopecia Tool (SALT) score ≤ 20 at week&#xa0;24 (responders) continue ritlecitinib 50-mg through week&#xa0;48; nonresponders at week&#xa0;24 are rerandomized 2:1 to increase to ritlecitinib 100-mg or continue ritlecitinib 50-mg through week&#xa0;48.</p> Planned Outcomes <p>The primary end point is a SALT score ≤ 20 at week&#xa0;24 for ritlecitinib 100-mg versus external placebo. Key secondary end points include SALT score ≤ 20 at week&#xa0;24 for ritlecitinib 50-mg versus external placebo and week&#xa0;36 for ritlecitinib 100-mg versus synthetic placebo, and SALT score change from baseline at week&#xa0;24 for ritlecitinib 100-mg versus 50-mg. An external ritlecitinib 50-mg nonresponders control group augments the ritlecitinib 50-mg nonresponders at week&#xa0;24 rerandomized to ritlecitinib 50-mg to support comparative analyses at week&#xa0;48.</p> Clinicaltrials.gov Registration <p>NCT06873945.</p> <p><MediaObject ID="MOESM1"> <VideoObject FileRef="MediaObjects/13555_2025_1543_MOESM1_ESM.mp4" VideoID="1qp9UjXCwQpVDYPYkL6cNG"> <Caption Language="En" xml:lang="en"> <CaptionContent> <p>Video Abstract (MP4 303790&#xa0;kb)</p> </CaptionContent> </Caption> </VideoObject> </MediaObject></p>

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Rationale and Design of a Novel, Phase 3, External and Synthetic Placebo-Controlled Clinical Trial of Ritlecitinib 50 mg and 100 mg for Alopecia Areata

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月14日

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  • Brett King,
  • Amy McMichael,
  • Rodney Sinclair,
  • Sergio Vañó-Galvan,
  • Robert Wolk,
  • Deborah Woodworth,
  • Koshika Soma,
  • Feriel Robbana,
  • Alexandre Lejeune,
  • Lynne Napatalung,
  • Ernest Law,
  • Dalia Wajsbrot,
  • Cunshan Wang,
  • Satrajit Roychoudhury

摘要

Introduction

Despite recent advancements in treating severe alopecia areata (AA), many patients do not achieve target efficacy with approved therapies. Ritlecitinib is an oral Janus kinase 3 (JAK3)/tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinase inhibitor approved to treat severe AA at a dose of 50-mg once daily (QD). A new phase 3 clinical trial (NCT06873945) described herein evaluates a higher dose of ritlecitinib (100-mg QD) in patients with AA. The study employs an innovative design using patient-level data from patients with similar baseline characteristics from previous AA ritlecitinib studies to form an external placebo control group, a synthetic placebo control group (extrapolating for outcomes over a longer timeframe than captured previously), and an external ritlecitinib 50-mg nonresponders group, eliminating the need to randomize patients to placebo.

Methods

This randomized, double-blind clinical trial investigates the efficacy and safety of ritlecitinib in patients aged ≥ 12 years with AA and ≥ 50% scalp hair loss. Patients are randomized to ritlecitinib 100-mg or 50-mg QD. Those randomized to ritlecitinib 100-mg continue the 100-mg dose through week 48. Patients randomized to ritlecitinib 50-mg with a Severity of Alopecia Tool (SALT) score ≤ 20 at week 24 (responders) continue ritlecitinib 50-mg through week 48; nonresponders at week 24 are rerandomized 2:1 to increase to ritlecitinib 100-mg or continue ritlecitinib 50-mg through week 48.

Planned Outcomes

The primary end point is a SALT score ≤ 20 at week 24 for ritlecitinib 100-mg versus external placebo. Key secondary end points include SALT score ≤ 20 at week 24 for ritlecitinib 50-mg versus external placebo and week 36 for ritlecitinib 100-mg versus synthetic placebo, and SALT score change from baseline at week 24 for ritlecitinib 100-mg versus 50-mg. An external ritlecitinib 50-mg nonresponders control group augments the ritlecitinib 50-mg nonresponders at week 24 rerandomized to ritlecitinib 50-mg to support comparative analyses at week 48.

Clinicaltrials.gov Registration

NCT06873945.

Video Abstract (MP4 303790 kb)