Phase 3 Trials of Tirbanibulin Ointment for Actinic Keratosis.

Acetamides / adverse effects Administration, Topical Aged Double-Blind Method Enzyme Inhibitors / adverse effects Face / pathology Female Humans Kaplan-Meier Estimate Keratosis, Actinic / drug therapy Male Middle Aged Morpholines / adverse effects Ointments / therapeutic use Polymerization / drug effects Pyridines / adverse effects Scalp / pathology Skin / pathology Tubulin / metabolism

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
11 02 2021
Historique:
entrez: 10 2 2021
pubmed: 11 2 2021
medline: 18 2 2021
Statut: ppublish

Résumé

The tubulin polymerization and Src kinase signaling inhibitor tirbanibulin is being investigated as a topical treatment for actinic keratosis, a precursor of squamous-cell carcinoma. In two identically designed double-blind trials, we randomly assigned, in a 1:1 ratio, adults with actinic keratoses on the face or scalp to receive either topical tirbanibulin or vehicle (placebo) ointment. The ointment was applied by the patients to a 25-cm A total of 702 patients were enrolled in the two trials (351 patients per trial). Complete clearance in trial 1 occurred in 44% of the patients (77 of 175) in the tirbanibulin group and in 5% of those (8 of 176) in the vehicle group (difference, 40 percentage points; 95% confidence interval [CI], 32 to 47; P<0.001); in trial 2, the percentages were 54% (97 of 178 patients) and 13% (22 of 173), respectively (difference, 42 percentage points; 95% CI, 33 to 51; P<0.001). The percentages of patients with partial clearance were significantly higher in the tirbanibulin groups than in the vehicle groups. At 1 year, the estimated percentage of patients with recurrent lesions was 47% among patients who had had a complete response to tirbanibulin. The most common local reactions to tirbanibulin were erythema in 91% of the patients and flaking or scaling in 82%. Adverse events with tirbanibulin were application-site pain in 10% of the patients and pruritus in 9%, all of which resolved. In two identically designed trials, tirbanibulin 1% ointment applied once daily for 5 days was superior to vehicle for the treatment of actinic keratosis at 2 months but was associated with transient local reactions and recurrence of lesions at 1 year. Trials comparing tirbanibulin with conventional treatments and that have longer follow-up are needed to determine the effects of tirbanibulin therapy on actinic keratosis. (Funded by Athenex; ClinicalTrials.gov numbers, NCT03285477 and NCT03285490.).

Sections du résumé

BACKGROUND
The tubulin polymerization and Src kinase signaling inhibitor tirbanibulin is being investigated as a topical treatment for actinic keratosis, a precursor of squamous-cell carcinoma.
METHODS
In two identically designed double-blind trials, we randomly assigned, in a 1:1 ratio, adults with actinic keratoses on the face or scalp to receive either topical tirbanibulin or vehicle (placebo) ointment. The ointment was applied by the patients to a 25-cm
RESULTS
A total of 702 patients were enrolled in the two trials (351 patients per trial). Complete clearance in trial 1 occurred in 44% of the patients (77 of 175) in the tirbanibulin group and in 5% of those (8 of 176) in the vehicle group (difference, 40 percentage points; 95% confidence interval [CI], 32 to 47; P<0.001); in trial 2, the percentages were 54% (97 of 178 patients) and 13% (22 of 173), respectively (difference, 42 percentage points; 95% CI, 33 to 51; P<0.001). The percentages of patients with partial clearance were significantly higher in the tirbanibulin groups than in the vehicle groups. At 1 year, the estimated percentage of patients with recurrent lesions was 47% among patients who had had a complete response to tirbanibulin. The most common local reactions to tirbanibulin were erythema in 91% of the patients and flaking or scaling in 82%. Adverse events with tirbanibulin were application-site pain in 10% of the patients and pruritus in 9%, all of which resolved.
CONCLUSIONS
In two identically designed trials, tirbanibulin 1% ointment applied once daily for 5 days was superior to vehicle for the treatment of actinic keratosis at 2 months but was associated with transient local reactions and recurrence of lesions at 1 year. Trials comparing tirbanibulin with conventional treatments and that have longer follow-up are needed to determine the effects of tirbanibulin therapy on actinic keratosis. (Funded by Athenex; ClinicalTrials.gov numbers, NCT03285477 and NCT03285490.).

Identifiants

DOI: 10.1056/NEJMoa2024040 PMID: 33567191
pubmed: 33567191
doi: 10.1056/NEJMoa2024040
doi:

Substances chimiques

Acetamides 0
Enzyme Inhibitors 0
Morpholines 0
Ointments 0
Pyridines 0
Tubulin 0
tirbanibulin 0

Banques de données

ClinicalTrials.gov
['NCT03285477', 'NCT03285490']

Types de publication

Clinical Trial, Phase III Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

512-520

Investigateurs

Glynis Ablon (G)
Jerry Bagel (J)
Michael Bukhalo (M)
J Clay Davis (JC)
Sunil Dhawan (S)
Robert Fixler (R)
David Greenstein (D)
Scott Guenthner (S)
George Han (G)
Catherine Hren (C)
Stephen Huang (S)
John Humeniuk (J)
Sarah Jackson (S)
Timothy Jochen (T)
Terry Jones (T)
Steven Kempers (S)
Edward Lain (E)
Debra Liu (D)
Chere Lucas-Anthony (C)
James Pehoushek (J)
Catherine Pointon (C)
Jeffrey Rosen (J)
Joel Schlessinger (J)
James Solomon (J)
Leonard Swinyer (L)
Douglas Thomas (D)
Aldo Trovato (A)
Eduardo Tschen (E)
John Tu (J)
Stephen Tyring (S)
Matthew Zook (M)
Joshua Berlin (J)
Andrew Blauvelt (A)
Suzanne Bruce (S)
Norman Bystol (N)
Anne Chapas (A)
Joel Cohen (J)
Jess DeMaria (J)
Janet DuBois (J)
Seth Forman (S)
Joseph Fowler (J)
Scott Fretzin (S)
Peter Jenkin (P)
Fasahat Hamzavi (F)
C William Hanke (CW)
Abel Jarell (A)
S Sasha Jazayeri (SS)
Robert Lieberman (R)
Keith Loven (K)
Kappa Meadows (K)
Adnan Nasir (A)
Terri Nutt (T)
Maureen Olivier (M)
Edward Primka (E)
Todd Schlesinger (T)
Kenneth Stein (K)
Melody Lynn Stone (ML)
Dow Stough (D)
Jens Thiele (J)
Anne Truitt (A)
Darryl Wong (D)
Martin Zaiac (M)

Informations de copyright

Copyright © 2021 Massachusetts Medical Society.

Auteurs

Andrew Blauvelt (A)

From the Oregon Medical Research Center, Portland (A.B.); the Minnesota Clinical Study Center, New Brighton (S.K.); the Austin Institute for Clinical Research, Pflugerville (E.L.), and the Department of Dermatology and Center for Clinical Studies, University of Texas Health Science Center at Houston, Houston (S.T.) - both in Texas; the Clinical Research Center of the Carolinas, Charleston, SC (T.S.); ForCare Clinical Research, Tampa, FL (S.F.); Ablon Skin Institute Research Center, Manhattan Beach, CA (G.A.); Dr. George Martin Dermatology Associates, Kihei, HI (G.M.); and Athenex, Buffalo, NY (H.W., D.L.C., J.F., M.-F.R.K.).

Steven Kempers (S)

From the Oregon Medical Research Center, Portland (A.B.); the Minnesota Clinical Study Center, New Brighton (S.K.); the Austin Institute for Clinical Research, Pflugerville (E.L.), and the Department of Dermatology and Center for Clinical Studies, University of Texas Health Science Center at Houston, Houston (S.T.) - both in Texas; the Clinical Research Center of the Carolinas, Charleston, SC (T.S.); ForCare Clinical Research, Tampa, FL (S.F.); Ablon Skin Institute Research Center, Manhattan Beach, CA (G.A.); Dr. George Martin Dermatology Associates, Kihei, HI (G.M.); and Athenex, Buffalo, NY (H.W., D.L.C., J.F., M.-F.R.K.).

Edward Lain (E)

From the Oregon Medical Research Center, Portland (A.B.); the Minnesota Clinical Study Center, New Brighton (S.K.); the Austin Institute for Clinical Research, Pflugerville (E.L.), and the Department of Dermatology and Center for Clinical Studies, University of Texas Health Science Center at Houston, Houston (S.T.) - both in Texas; the Clinical Research Center of the Carolinas, Charleston, SC (T.S.); ForCare Clinical Research, Tampa, FL (S.F.); Ablon Skin Institute Research Center, Manhattan Beach, CA (G.A.); Dr. George Martin Dermatology Associates, Kihei, HI (G.M.); and Athenex, Buffalo, NY (H.W., D.L.C., J.F., M.-F.R.K.).

Todd Schlesinger (T)

From the Oregon Medical Research Center, Portland (A.B.); the Minnesota Clinical Study Center, New Brighton (S.K.); the Austin Institute for Clinical Research, Pflugerville (E.L.), and the Department of Dermatology and Center for Clinical Studies, University of Texas Health Science Center at Houston, Houston (S.T.) - both in Texas; the Clinical Research Center of the Carolinas, Charleston, SC (T.S.); ForCare Clinical Research, Tampa, FL (S.F.); Ablon Skin Institute Research Center, Manhattan Beach, CA (G.A.); Dr. George Martin Dermatology Associates, Kihei, HI (G.M.); and Athenex, Buffalo, NY (H.W., D.L.C., J.F., M.-F.R.K.).

Stephen Tyring (S)

From the Oregon Medical Research Center, Portland (A.B.); the Minnesota Clinical Study Center, New Brighton (S.K.); the Austin Institute for Clinical Research, Pflugerville (E.L.), and the Department of Dermatology and Center for Clinical Studies, University of Texas Health Science Center at Houston, Houston (S.T.) - both in Texas; the Clinical Research Center of the Carolinas, Charleston, SC (T.S.); ForCare Clinical Research, Tampa, FL (S.F.); Ablon Skin Institute Research Center, Manhattan Beach, CA (G.A.); Dr. George Martin Dermatology Associates, Kihei, HI (G.M.); and Athenex, Buffalo, NY (H.W., D.L.C., J.F., M.-F.R.K.).

Seth Forman (S)

From the Oregon Medical Research Center, Portland (A.B.); the Minnesota Clinical Study Center, New Brighton (S.K.); the Austin Institute for Clinical Research, Pflugerville (E.L.), and the Department of Dermatology and Center for Clinical Studies, University of Texas Health Science Center at Houston, Houston (S.T.) - both in Texas; the Clinical Research Center of the Carolinas, Charleston, SC (T.S.); ForCare Clinical Research, Tampa, FL (S.F.); Ablon Skin Institute Research Center, Manhattan Beach, CA (G.A.); Dr. George Martin Dermatology Associates, Kihei, HI (G.M.); and Athenex, Buffalo, NY (H.W., D.L.C., J.F., M.-F.R.K.).

Glynis Ablon (G)

From the Oregon Medical Research Center, Portland (A.B.); the Minnesota Clinical Study Center, New Brighton (S.K.); the Austin Institute for Clinical Research, Pflugerville (E.L.), and the Department of Dermatology and Center for Clinical Studies, University of Texas Health Science Center at Houston, Houston (S.T.) - both in Texas; the Clinical Research Center of the Carolinas, Charleston, SC (T.S.); ForCare Clinical Research, Tampa, FL (S.F.); Ablon Skin Institute Research Center, Manhattan Beach, CA (G.A.); Dr. George Martin Dermatology Associates, Kihei, HI (G.M.); and Athenex, Buffalo, NY (H.W., D.L.C., J.F., M.-F.R.K.).

George Martin (G)

From the Oregon Medical Research Center, Portland (A.B.); the Minnesota Clinical Study Center, New Brighton (S.K.); the Austin Institute for Clinical Research, Pflugerville (E.L.), and the Department of Dermatology and Center for Clinical Studies, University of Texas Health Science Center at Houston, Houston (S.T.) - both in Texas; the Clinical Research Center of the Carolinas, Charleston, SC (T.S.); ForCare Clinical Research, Tampa, FL (S.F.); Ablon Skin Institute Research Center, Manhattan Beach, CA (G.A.); Dr. George Martin Dermatology Associates, Kihei, HI (G.M.); and Athenex, Buffalo, NY (H.W., D.L.C., J.F., M.-F.R.K.).

Hui Wang (H)

From the Oregon Medical Research Center, Portland (A.B.); the Minnesota Clinical Study Center, New Brighton (S.K.); the Austin Institute for Clinical Research, Pflugerville (E.L.), and the Department of Dermatology and Center for Clinical Studies, University of Texas Health Science Center at Houston, Houston (S.T.) - both in Texas; the Clinical Research Center of the Carolinas, Charleston, SC (T.S.); ForCare Clinical Research, Tampa, FL (S.F.); Ablon Skin Institute Research Center, Manhattan Beach, CA (G.A.); Dr. George Martin Dermatology Associates, Kihei, HI (G.M.); and Athenex, Buffalo, NY (H.W., D.L.C., J.F., M.-F.R.K.).

David L Cutler (DL)

From the Oregon Medical Research Center, Portland (A.B.); the Minnesota Clinical Study Center, New Brighton (S.K.); the Austin Institute for Clinical Research, Pflugerville (E.L.), and the Department of Dermatology and Center for Clinical Studies, University of Texas Health Science Center at Houston, Houston (S.T.) - both in Texas; the Clinical Research Center of the Carolinas, Charleston, SC (T.S.); ForCare Clinical Research, Tampa, FL (S.F.); Ablon Skin Institute Research Center, Manhattan Beach, CA (G.A.); Dr. George Martin Dermatology Associates, Kihei, HI (G.M.); and Athenex, Buffalo, NY (H.W., D.L.C., J.F., M.-F.R.K.).

Jane Fang (J)

From the Oregon Medical Research Center, Portland (A.B.); the Minnesota Clinical Study Center, New Brighton (S.K.); the Austin Institute for Clinical Research, Pflugerville (E.L.), and the Department of Dermatology and Center for Clinical Studies, University of Texas Health Science Center at Houston, Houston (S.T.) - both in Texas; the Clinical Research Center of the Carolinas, Charleston, SC (T.S.); ForCare Clinical Research, Tampa, FL (S.F.); Ablon Skin Institute Research Center, Manhattan Beach, CA (G.A.); Dr. George Martin Dermatology Associates, Kihei, HI (G.M.); and Athenex, Buffalo, NY (H.W., D.L.C., J.F., M.-F.R.K.).

Min-Fun R Kwan (MR)

From the Oregon Medical Research Center, Portland (A.B.); the Minnesota Clinical Study Center, New Brighton (S.K.); the Austin Institute for Clinical Research, Pflugerville (E.L.), and the Department of Dermatology and Center for Clinical Studies, University of Texas Health Science Center at Houston, Houston (S.T.) - both in Texas; the Clinical Research Center of the Carolinas, Charleston, SC (T.S.); ForCare Clinical Research, Tampa, FL (S.F.); Ablon Skin Institute Research Center, Manhattan Beach, CA (G.A.); Dr. George Martin Dermatology Associates, Kihei, HI (G.M.); and Athenex, Buffalo, NY (H.W., D.L.C., J.F., M.-F.R.K.).

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Classifications MeSH

Recherchemedicale.com › Composés chimiques organiques › Acides carboxyliques › Acides acycliques › Acétamides › Phase 3 Trials of Tirbanibulin Ointment for...
Recherchemedicale.com › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Administration par voie topique › Phase 3 Trials of Tirbanibulin Ointment for...
Recherchemedicale.com › Personnes › Tranches d'âge › Adulte › Sujet âgé › Phase 3 Trials of Tirbanibulin Ointment for...
Recherchemedicale.com › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Méthode en double aveugle › Phase 3 Trials of Tirbanibulin Ointment for...
Recherchemedicale.com › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Phase 3 Trials of Tirbanibulin Ointment for...
Recherchemedicale.com › Régions du corps › Tête › Face › Phase 3 Trials of Tirbanibulin Ointment for...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Phase 3 Trials of Tirbanibulin Ointment for...
Recherchemedicale.com › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de survie › Estimation de Kaplan-Meier › Phase 3 Trials of Tirbanibulin Ointment for...
Recherchemedicale.com › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Kératose › Kératose actinique › Phase 3 Trials of Tirbanibulin Ointment for...
Recherchemedicale.com › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Phase 3 Trials of Tirbanibulin Ointment for...
Recherchemedicale.com › Composés hétérocycliques › Composés hétéromonocycliques › Oxazines › Morpholines › Phase 3 Trials of Tirbanibulin Ointment for...
Recherchemedicale.com › Préparations pharmaceutiques › Onguents › Phase 3 Trials of Tirbanibulin Ointment for...
Recherchemedicale.com › Phénomènes chimiques › Polymérisation › Phase 3 Trials of Tirbanibulin Ointment for...
Recherchemedicale.com › Composés hétérocycliques › Composés hétéromonocycliques › Pyridines › Phase 3 Trials of Tirbanibulin Ointment for...
Recherchemedicale.com › Régions du corps › Tête › Cuir chevelu › Phase 3 Trials of Tirbanibulin Ointment for...
Recherchemedicale.com › Système tégumentaire › Peau › Phase 3 Trials of Tirbanibulin Ointment for...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Tubuline › Phase 3 Trials of Tirbanibulin Ointment for...