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ClinPharm Vault

Barzolvolimab

Overview

  • Priority class: KIT
  • Mechanistic bucket: KIT-targeted mast-cell pathway program
  • Sponsor: Celldex Therapeutics
  • Development focus: Active clinical development represented in current raw-source layer
  • Indications represented in current raw sources: Chronic Spontaneous Urticaria, Cold Urticaria, Cold Contact Urticaria, Symptomatic Dermographism, Symptomatic Dermatographism, Cholinergic Urticaria, Chronic Inducible Urticaria, Cold-Induced Urticaria

Strategy readout

  • Headline: Parallel KIT franchise build across CSU and CIndU, now extending into multiple phase 3 tracks.
  • Current strategic read: The current local source layer suggests Celldex is not treating barzolvolimab as a single-study CSU asset. Instead, it is using early KIT proof across both spontaneous and inducible urticaria to support a broader late-stage urticaria franchise.
  • Highest visible phase in current registry: Phase 3
  • Strategy confidence in current local layer: High

Why this looks like the strategy

  • Completed early studies cover both CSU and CIndU, so proof-of-concept was established across more than one urticaria phenotype before the current phase 3 wave.
  • Two active phase 3 CSU studies plus a separate recruiting phase 3 CIndU study suggest deliberate parallel expansion rather than sequential single-indication development.
  • The LTE study indicates lifecycle and durability planning, not just a one-shot registrational attempt.

What to watch next

  • How the sponsor differentiates the CSU pair versus the CIndU phase 3 branch in eventual positioning and labeling logic.
  • Whether later derived pages can tie sponsor posters and press releases more tightly to explicit trial IDs.

Operational study design view

Trial Arms in registry Active dose regimens Total enrollment Per-arm sample size summary
NCT04538794 2 4 45 45 randomized total, with 35 barzolvolimab-treated and 10 placebo-treated overall; publication abstract also lists four dose cohorts (0.5 mg/kg Q4W, 1.5 mg/kg Q4W, 3 mg/kg Q8W, 4.5 mg/kg Q8W).
NCT04548869 1 1 41 ClinicalTrials.gov arm description states planned enrollment of 20 Cold Contact Urticaria, 10 Symptomatic Dermographism, and 10 Cholinergic Urticaria patients; CT.gov lists 41 actual participants overall.
NCT05368285 6 3 208 Publication abstract supports placebo-controlled core randomization of 75 mg Q4W (n=53), 150 mg Q4W (n=52), 300 mg Q8W (n=51), and placebo (n=51). The currently generated 52-week CT.gov labels only map cleanly to the sustained 150 mg and 300 mg arms; the re-randomized 75 mg and placebo extension arms remain unresolved at exact row level in the current local evidence layer.
NCT05405660 6 2 196 ACAAI poster text supports ColdU n=96 split as 150 mg Q4W n=32, 300 mg Q8W n=32, placebo n=32, and symptomatic dermographism n=97 split as 150 mg Q4W n=33, 300 mg Q8W n=33, placebo n=31.
NCT06445023 4 4 963 963 total across 4 listed arms; exact arm-specific counts are not explicitly stated in the current local source text.
NCT06455202 4 4 976 976 total across 4 listed arms; exact arm-specific counts are not explicitly stated in the current local source text.
NCT07256392 2 1 1370 1370 total across 2 listed arms; exact arm-specific counts are not explicitly stated in the current local source text.
NCT07266402 4 1 240 240 total across 4 listed arms; exact arm-specific counts are not explicitly stated in the current local source text.

Study Inventory

Completed / historical studies

  • NCT04538794 - Phase 1; COMPLETED; Chronic Spontaneous Urticaria
  • NCT04548869 - Phase 1; COMPLETED; Cold Urticaria, Cold Contact Urticaria, Symptomatic Dermographism, Symptomatic Dermatographism, Cholinergic Urticaria
  • NCT05368285 - Phase 2; COMPLETED; Chronic Spontaneous Urticaria
  • NCT05405660 - Phase 2; COMPLETED; Chronic Inducible Urticaria

Active / recruiting studies

  • NCT06445023 - Phase 3; ACTIVE_NOT_RECRUITING; Chronic Spontaneous Urticaria
  • NCT06455202 - Phase 3; ACTIVE_NOT_RECRUITING; Chronic Spontaneous Urticaria
  • NCT07256392 - Phase 3; RECRUITING; Chronic Spontaneous Urticaria
  • NCT07266402 - Phase 3; RECRUITING; Chronic Inducible Urticaria, Cold Urticaria, Cold-Induced Urticaria, Symptomatic Dermographism

Other registry entries

  • None in current registry

Program Results Summary

Trials with source-backed results in the current local layer: 3 of 8

NCT04538794 (Published) - At week 12 across all barzolvolimab doses combined: 71% achieved well-controlled disease (UAS7 <= 6), 57% achieved complete response (UAS7 = 0). - Well tolerated; hair color change was the most common AE (mechanism-related KIT effect). - Sources: PMID 40415544

NCT05368285 (Published) - Primary endpoint met at week 12 (UAS7 change from baseline, LS mean delta versus placebo): 150 mg Q4W -12.55 (P < 0.0001), 300 mg Q8W -13.41 (P < 0.0001), 75 mg Q4W -6.60 (P = 0.0017). - Hair color changes (26%), neutropenia (17%), skin hypopigmentation (13%); all mechanism-related, mostly Grade 1, reversible upon discontinuation. - Sources: PMID 41747871; raw/sponsors/kit/barzolvolimab/aaaai-2025-csu-poster.md; raw/sponsors/kit/barzolvolimab/eadv-2024-congress-presentation.md; raw/sponsors/kit/barzolvolimab/eadv-2025-csu-ige-poster.md

NCT05405660 (Conference) - Primary endpoint (negative provocation test at week 12) -- Cold urticaria: 150 mg Q4W 53.1%, 300 mg Q8W 46.9%, placebo 12.5%. - 98% of TEAEs were Grade 1 or 2; hair color changes 13% (versus 0% placebo), neutropenia 10% (versus 0% placebo). - Sources: raw/sponsors/kit/barzolvolimab/phase-2-cindu-acaai-poster.md; raw/sponsors/kit/barzolvolimab/ir-press-release-pdf-additional-data.md

Sponsor-sourced result evidence

CSU sponsor-poster layer is unusually deep, extending the manuscript-backed phase 2 story into durability, quality-of-life, and IgE-subgroup analyses.

AAAAI 2025 CSU poster (52-week control and quality-of-life follow-up) (Conference poster) - Improvement in urticaria control was sustained through week 52, with up to 82% of patients reporting well-controlled urticaria by UCT and approximately half reporting complete control at week 52. - The poster also frames week-52 quality-of-life improvement, with many patients reporting that CSU symptoms no longer had meaningful impact on daily life. - This poster strengthens the interpretation that the phase 2 CSU dataset is not only statistically positive at week 12, but also durable and patient-meaningful over longer follow-up. - Safety: Mechanism-related events highlighted in the sponsor poster remained mainly hair color change, neutropenia, urticaria, and skin pigment change, consistent with the broader barzolvolimab safety narrative. - Source(s): raw/sponsors/kit/barzolvolimab/aaaai-2025-csu-poster.md

EADV 2025 CSU IgE subgroup poster (Conference poster) - Weeks 12 and 52 analyses suggest similarly strong efficacy for 150 mg Q4W and 300 mg Q8W in patients with low (< 40 IU/mL) and normal/high (>= 40 IU/mL) baseline IgE levels. - The cached poster text states that adjusted p-values were non-significant for comparisons between IgE subgroups, while most active-versus-placebo comparisons remained significant, supporting efficacy across biologically distinct CSU subsets. - This is especially useful strategically because low-IgE CSU is often discussed as a more autoimmune / anti-IgE-refractory phenotype. - Source(s): raw/sponsors/kit/barzolvolimab/eadv-2025-csu-ige-poster.md

Late follow-up sponsor disclosures (ACAAI/AAAAI-linked releases) (Sponsor press release / IR PDF) - Sponsor disclosures extend the CSU phase 2 story beyond active treatment, including up to 41% complete response at week 76 and persistence of control after treatment discontinuation in a subset of week-52 responders. - One sponsor summary also highlights a subset analysis in which 88% of patients who completed 52 weeks on 150 mg Q4W or 300 mg Q8W and finished treatment with at least well-controlled disease reported complete response. - Safety: Sponsor summaries continue to describe the safety profile as well tolerated, with KIT-related tolerability findings largely reversible after discontinuation. - Source(s): raw/sponsors/kit/barzolvolimab/ir-press-release-additional-positive-data.md; raw/sponsors/kit/barzolvolimab/ir-press-release-pdf-additional-data.md

Longitudinal efficacy view

  • Plotted page: Barzolvolimab longitudinal UAS7
  • Shared comparison page: Cross-program longitudinal UAS7 comparison
  • Current explicit numeric plotting coverage: week 12 UAS7 change-from-baseline by core randomized arm, plus week 12 and week 52 UAS7 <= 6 and UAS7 = 0 landmarks.
  • Current main caveat: the week 52 values for the former 75 mg and placebo groups are post-week-16 transition-group landmarks, not unchanged original-arm trajectories.
  • Current main gap: the full week-by-week mean UAS7 curve is still graph-only in the current local extraction and remains intentionally unplotted.
  • Local data backbone: data/barzolvolimab_longitudinal_uas7.json and data/barzolvolimab_longitudinal_uas7_notes.md.

Evidence Coverage

  • CT.gov trials in registry: 8
  • Sponsor artifacts in registry: 7
  • Primary publications in registry: 3
  • Supporting publications in registry: 2
  • Publication status: primary_manuscripts_found
  • Publication summary: Strong manuscript coverage across early CIndU proof-of-concept, CSU phase 1b MAD, and CSU phase 2 dose-finding.

Primary publications

  • PMID 36385701 (2023, Allergy): Anti-KIT antibody, barzolvolimab, reduces skin mast cells and disease activity in chronic inducible urticaria.
  • Role: cindu_open_label_proof_of_concept
  • Linked trial IDs: NR
  • Local cache: raw/publications/pubmed/markdown/PMID36385701.md
  • PMID 40415544 (2025, Allergy): Anti-KIT Barzolvolimab for Chronic Spontaneous Urticaria.
  • Role: csu_phase_1b_mad
  • Linked trial IDs: NCT04538794
  • Local cache: raw/publications/pubmed/markdown/PMID40415544.md
  • PMID 41747871 (2026, The Journal of allergy and clinical immunology): Randomized dose-finding study of anti-KIT barzolvolimab in patients with chronic spontaneous urticaria.
  • Role: csu_phase_2_core
  • Linked trial IDs: NCT05368285
  • Local cache: raw/publications/pubmed/markdown/PMID41747871.md

Supporting evidence

  • PMID 37897679: Inhibition of KIT for chronic urticaria: a status update on drugs in early clinical development. (raw/publications/pubmed/markdown/PMID37897679.md)
  • PMID 38937013: Emerging Therapeutics in Chronic Urticaria. (raw/publications/pubmed/markdown/PMID38937013.md)
  • Sponsor artifact: IR press release positive results (Celldex)
  • raw/sponsors/kit/barzolvolimab/ir-press-release-positive-results.html
  • raw/sponsors/kit/barzolvolimab/ir-press-release-positive-results.md
  • Sponsor artifact: IR press release additional positive data (Celldex)
  • raw/sponsors/kit/barzolvolimab/ir-press-release-additional-positive-data.html
  • raw/sponsors/kit/barzolvolimab/ir-press-release-additional-positive-data.md
  • Sponsor artifact: AAAAI 2025 CSU poster (Celldex)
  • raw/sponsors/kit/barzolvolimab/aaaai-2025-csu-poster.pdf
  • raw/sponsors/kit/barzolvolimab/aaaai-2025-csu-poster.txt
  • raw/sponsors/kit/barzolvolimab/aaaai-2025-csu-poster.md
  • Sponsor artifact: Phase 2 CIndU ACAAI poster (Celldex)
  • raw/sponsors/kit/barzolvolimab/phase-2-cindu-acaai-poster.pdf
  • raw/sponsors/kit/barzolvolimab/phase-2-cindu-acaai-poster.txt
  • raw/sponsors/kit/barzolvolimab/phase-2-cindu-acaai-poster.md
  • Sponsor artifact: EADV 2024 congress presentation (Celldex)
  • raw/sponsors/kit/barzolvolimab/eadv-2024-congress-presentation.pdf
  • raw/sponsors/kit/barzolvolimab/eadv-2024-congress-presentation.txt
  • raw/sponsors/kit/barzolvolimab/eadv-2024-congress-presentation.md
  • Sponsor artifact: EADV 2025 CSU IgE subgroup poster (Celldex)
  • raw/sponsors/kit/barzolvolimab/eadv-2025-csu-ige-poster.pdf
  • raw/sponsors/kit/barzolvolimab/eadv-2025-csu-ige-poster.txt
  • raw/sponsors/kit/barzolvolimab/eadv-2025-csu-ige-poster.md
  • Sponsor artifact: IR press release PDF additional data (Celldex)
  • raw/sponsors/kit/barzolvolimab/ir-press-release-pdf-additional-data.pdf
  • raw/sponsors/kit/barzolvolimab/ir-press-release-pdf-additional-data.txt
  • raw/sponsors/kit/barzolvolimab/ir-press-release-pdf-additional-data.md

Interpretation

  • Verified facts: the current v2 registry tracks 8 CT.gov entries for this program and links them conservatively to sponsor and publication evidence where explicit identifiers are available.
  • Interpretation: this program already has enough linked manuscript or registry support for a source-first derived program page, but individual study pages should still be reviewed and enriched over time.
  • Open questions:
  • Unclassified publication PMIDs remain in the search set: 40074986, 39598410, 40747638, 35166638, 36719690, 40702781, 41654334, 41270830, 33685605
  • Several sponsor artifacts remain program-level because no explicit study identifier was captured in cached metadata.

Provenance

  • Primary source(s):
  • ../inventories/source_registry.json
  • ../inventories/source_registry.md
  • Supporting source(s):
  • ../inventories/ctgov_priority_trials.json
  • ../inventories/publication_priority_curation.json
  • ../inventories/sponsor_priority_sources.json
  • Last verified: 2026-04-08
  • Verification status: Partial

Change Log

  • 2026-04-08: Generated or refreshed this program page from the v2 source registry and local source caches.