HIS news
Pfizer Initiates Phase 2b Trial of Ritlecitinib in Antihistamine-Refractory Chronic Spontaneous Urticaria
Pfizer has launched a randomized, double-blind, placebo-controlled Phase 2b trial evaluating oral ritlecitinib (50 mg and 100 mg once daily) in adults with chronic spontaneous urticaria inadequately controlled by second-generation antihistamines. Approximately 150 participants will be enrolled across a 24-week double-blind treatment period.
Pfizer has initiated active recruitment for a Phase 2b trial (NCT07219615) investigating ritlecitinib, an oral JAK3/TEC-family kinase inhibitor, as a potential therapeutic option for adults with chronic spontaneous urticaria (CSU) that remains inadequately controlled despite second-generation antihistamine (sgAH) therapy. The trial is designed as a randomized, double-blind, placebo-controlled study with a 12-week core treatment period (Period A) followed by a 12-week double-blind extension (Period B).
Eligible participants must be 18 years or older with a confirmed CSU diagnosis of at least 3 months' duration and documented inadequate response to antihistamine therapy. Individuals with concurrent pruritic dermatoses or urticaria attributable to identifiable triggers are excluded. All participants are required to discontinue existing CSU therapies, with the exception of a background sgAH. Ritlecitinib will be evaluated at oral doses of 50 mg and 100 mg once daily versus placebo during Period A; participants originally randomized to placebo will be switched to ritlecitinib 100 mg for Period B, while active-arm participants continue their assigned doses.
The trial will enroll approximately 150 participants across up to 9 site visits over roughly 8 months. Assessments include physical examinations, audiometric testing, ECGs, laboratory evaluations, and daily electronic diary completion capturing CSU symptom burden. The inclusion of hearing assessments reflects the known auditory monitoring requirements associated with JAK inhibitor class surveillance. Primary endpoints encompassing efficacy, safety, and tolerability will inform dose selection for potential further development in this indication.
Key points
- Phase 2b randomized, double-blind, placebo-controlled trial of ritlecitinib (PF-06651600) in antihistamine-refractory CSU is actively recruiting (NCT07219615).
- Two oral once-daily doses—50 mg and 100 mg—are being evaluated against placebo over a 12-week primary period, with a 12-week double-blind extension.
- Target enrollment is approximately 150 adults with CSU uncontrolled by second-generation antihistamines for ≥3 months.
- Audiometric testing is included in the safety monitoring protocol, consistent with JAK inhibitor class surveillance requirements.
- Pfizer is the trial sponsor; ritlecitinib is already approved for alopecia areata in some jurisdictions, representing a potential label expansion into CSU.
Why it matters
CSU refractory to antihistamines represents a significant unmet need, and ritlecitinib's dual JAK3/TEC-family kinase inhibition offers a mechanistically distinct oral alternative to existing biologics such as omalizumab. Phase 2b dose-finding data will be critical for determining whether ritlecitinib can advance as a viable oral option in this population.