Efficacy, Safety, and Tolerability of Oral DFD-29, a Low-Dose Formulation of Minocycline, in Rosacea: Two Phase 3 Randomized Clinical Trials.

IF 11 1区医学 Q1 DERMATOLOGY JAMA dermatology Pub Date : 2025-05-01 DOI:10.1001/jamadermatol.2024.6542

Neal Bhatia, James Del Rosso, Linda Stein Gold, Edward Lain, Zoe Diana Draelos, Srinivas Sidgiddi

{"title":"Efficacy, Safety, and Tolerability of Oral DFD-29, a Low-Dose Formulation of Minocycline, in Rosacea: Two Phase 3 Randomized Clinical Trials.","authors":"Neal Bhatia, James Del Rosso, Linda Stein Gold, Edward Lain, Zoe Diana Draelos, Srinivas Sidgiddi","doi":"10.1001/jamadermatol.2024.6542","DOIUrl":null,"url":null,"abstract":"Introduction: A low-dose modified formulation of minocycline hydrochloride, DFD-29, is under evaluation for treating papulopustular rosacea (PPR).Objective: To determine the efficacy and safety of DFD-29, 40 mg, compared with doxycycline, 40 mg, and placebo for treating PPR.Design, setting, and participants: This study included data from 2 double-blind, placebo-controlled, phase 3 randomized clinical trials (MVOR-1 and MVOR-2) conducted between March 2022 and May 2023 at 61 centers in the US and Germany. Healthy adults 18 years and older with moderate to severe PPR were included.Interventions: Participants were randomized 3:3:2 to oral DFD-29 (minocycline hydrochloride capsules), 40 mg; doxycycline, 40 mg; or placebo once daily for 16 weeks.Main outcomes and measures: The coprimary efficacy outcomes were (1) proportion of participants with Investigator's Global Assessment (IGA) treatment success with DFD-29 vs placebo and (2) total inflammatory lesion count reductions with DFD-29 vs placebo. Secondary outcomes included comparisons between DFD-29 and doxycycline in coprimary outcomes and between DFD-29 and placebo in erythema reduction.Results: Of 653 participants enrolled, 323 were randomized in MVOR-1 (247 [76.5%] women; mean [SD] age, 47.2 [13.7] years) and 330 were randomized in MVOR-2 (249 [75.5%] women; mean [SD] age, 51.6 [14.0] years). DFD-29 demonstrated superior efficacy in IGA success rates compared with placebo (MVOR-1: treatment difference [TD], 32.9%; 95% CI, 19.6-46.2; P < .001; MVOR-2: TD, 34.1%; 95% CI, 21.3-46.8; P < .001) and compared with doxycycline (MVOR-1: TD, 18.0%; 95% CI, 5.0-31.1; P = .01; MVOR-2: TD, 28.3%; 95% CI, 17.4-39.3; P < .001). DFD-29 also showed superior efficacy in least-squares mean reductions in total inflammatory lesions vs placebo (MVOR-1: TD, -9.2; 95% CI, -11.5 to -6.9; P < .001; MVOR-2: TD, -6.8; 95% CI, -8.9 to -4.8; P < .001) and doxycycline (MVOR-1: TD, -4.7; 95% CI, -6.7 to -2.8; P < .001; MVOR-2: TD, -3.5; 95% CI, -5.4 to -1.6; P < .001). Adverse events with DFD-29, doxycycline, and placebo were reported in 32 of 121 (26.4%), 25 of 116 (21.6%), and 27 of 76 (35.5%), respectively, in MVOR-1 and 51 of 122 (41.8%), 40 of 121 (33.1%), and 30 of 82 (36.6%), respectively, in MVOR-2. The most common adverse events with DFD-29, doxycycline, and placebo were nasopharyngitis, reported in 4 of 121 (3.3%), 2 of 116 (1.7%), and 3 of 76 (3.9%), respectively, in MVOR-1 and 13 of 122 (10.7%), 10 of 121 (8.3%), and 13 of 82 (15.9%), respectively, in MVOR-2, and COVID-19, reported in 4 of 121 (3.3%), 3 of 116 (2.6%), and 4 of 76 (5.3%) in MVOR-1 and 7 of 122 (5.7%), 8 of 121 (6.6%), and 5 of 82 (6.1%) in MVOR-2.Conclusions and relevance: In this study, DFD-29 was superior in efficacy to both doxycycline and placebo and demonstrated a favorable risk-benefit profile in the treatment of PPR.Trial registration: ClinicalTrials.gov Identifiers: NCT05296629 and NCT05343455.","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":"499-507"},"PeriodicalIF":11.0000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883608/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JAMA dermatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1001/jamadermatol.2024.6542","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DERMATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: A low-dose modified formulation of minocycline hydrochloride, DFD-29, is under evaluation for treating papulopustular rosacea (PPR).

Objective: To determine the efficacy and safety of DFD-29, 40 mg, compared with doxycycline, 40 mg, and placebo for treating PPR.

Design, setting, and participants: This study included data from 2 double-blind, placebo-controlled, phase 3 randomized clinical trials (MVOR-1 and MVOR-2) conducted between March 2022 and May 2023 at 61 centers in the US and Germany. Healthy adults 18 years and older with moderate to severe PPR were included.

Interventions: Participants were randomized 3:3:2 to oral DFD-29 (minocycline hydrochloride capsules), 40 mg; doxycycline, 40 mg; or placebo once daily for 16 weeks.

Main outcomes and measures: The coprimary efficacy outcomes were (1) proportion of participants with Investigator's Global Assessment (IGA) treatment success with DFD-29 vs placebo and (2) total inflammatory lesion count reductions with DFD-29 vs placebo. Secondary outcomes included comparisons between DFD-29 and doxycycline in coprimary outcomes and between DFD-29 and placebo in erythema reduction.

Results: Of 653 participants enrolled, 323 were randomized in MVOR-1 (247 [76.5%] women; mean [SD] age, 47.2 [13.7] years) and 330 were randomized in MVOR-2 (249 [75.5%] women; mean [SD] age, 51.6 [14.0] years). DFD-29 demonstrated superior efficacy in IGA success rates compared with placebo (MVOR-1: treatment difference [TD], 32.9%; 95% CI, 19.6-46.2; P < .001; MVOR-2: TD, 34.1%; 95% CI, 21.3-46.8; P < .001) and compared with doxycycline (MVOR-1: TD, 18.0%; 95% CI, 5.0-31.1; P = .01; MVOR-2: TD, 28.3%; 95% CI, 17.4-39.3; P < .001). DFD-29 also showed superior efficacy in least-squares mean reductions in total inflammatory lesions vs placebo (MVOR-1: TD, -9.2; 95% CI, -11.5 to -6.9; P < .001; MVOR-2: TD, -6.8; 95% CI, -8.9 to -4.8; P < .001) and doxycycline (MVOR-1: TD, -4.7; 95% CI, -6.7 to -2.8; P < .001; MVOR-2: TD, -3.5; 95% CI, -5.4 to -1.6; P < .001). Adverse events with DFD-29, doxycycline, and placebo were reported in 32 of 121 (26.4%), 25 of 116 (21.6%), and 27 of 76 (35.5%), respectively, in MVOR-1 and 51 of 122 (41.8%), 40 of 121 (33.1%), and 30 of 82 (36.6%), respectively, in MVOR-2. The most common adverse events with DFD-29, doxycycline, and placebo were nasopharyngitis, reported in 4 of 121 (3.3%), 2 of 116 (1.7%), and 3 of 76 (3.9%), respectively, in MVOR-1 and 13 of 122 (10.7%), 10 of 121 (8.3%), and 13 of 82 (15.9%), respectively, in MVOR-2, and COVID-19, reported in 4 of 121 (3.3%), 3 of 116 (2.6%), and 4 of 76 (5.3%) in MVOR-1 and 7 of 122 (5.7%), 8 of 121 (6.6%), and 5 of 82 (6.1%) in MVOR-2.

Conclusions and relevance: In this study, DFD-29 was superior in efficacy to both doxycycline and placebo and demonstrated a favorable risk-benefit profile in the treatment of PPR.

Trial registration: ClinicalTrials.gov Identifiers: NCT05296629 and NCT05343455.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

口服二甲胺四环素低剂量制剂DFD-29治疗酒渣鼻的疗效、安全性和耐受性：两项3期随机临床试验

介绍：一种低剂量的盐酸米诺环素改良制剂，DFD-29，正在评估治疗丘疹性酒渣鼻（PPR）。目的：比较dfd - 29,40 mg与强力霉素40 mg、安慰剂治疗PPR的疗效和安全性。设计、环境和参与者：本研究纳入了2022年3月至2023年5月在美国和德国61个中心进行的2项双盲、安慰剂对照、3期随机临床试验（MVOR-1和MVOR-2）的数据。18岁及以上患有中度至重度PPR的健康成年人被纳入研究对象。干预措施：参与者按3:3:2随机分组，口服DFD-29（盐酸米诺环素胶囊），40mg；强力霉素，40毫克；或安慰剂，每天一次，持续16周。主要结局和测量：主要疗效结局是(1)与安慰剂相比，使用DFD-29获得研究者总体评估（IGA）治疗成功的参与者比例；(2)与安慰剂相比，使用DFD-29减少了炎症病灶总数。次要结果包括DFD-29和强力霉素在主要结果中的比较，以及DFD-29和安慰剂在红斑减少方面的比较。结果：入组的653名参与者中，323名被随机分为MVOR-1组(247名[76.5%]女性；平均[SD]年龄，47.2[13.7]岁)和330名MVOR-2随机分组(249名[75.5%]名女性；平均[SD]年龄，51.6[14.0]岁)。与安慰剂相比，DFD-29在IGA成功率方面表现出更高的疗效(MVOR-1：治疗差异[TD]， 32.9%；95% ci, 19.6-46.2；结论和相关性：在本研究中，DFD-29的疗效优于多西环素和安慰剂，并且在治疗PPR方面表现出良好的风险-收益特征。试验注册：ClinicalTrials.gov标识符：NCT05296629和NCT05343455。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

JAMA dermatology DERMATOLOGY-

CiteScore

14.10

自引率

5.50%

发文量

300

期刊介绍： JAMA Dermatology is an international peer-reviewed journal that has been in continuous publication since 1882. It began publication by the American Medical Association in 1920 as Archives of Dermatology and Syphilology. The journal publishes material that helps in the development and testing of the effectiveness of diagnosis and treatment in medical and surgical dermatology, pediatric and geriatric dermatology, and oncologic and aesthetic dermatologic surgery. JAMA Dermatology is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications. It is published online weekly, every Wednesday, and in 12 print/online issues a year. The mission of the journal is to elevate the art and science of health and diseases of skin, hair, nails, and mucous membranes, and their treatment, with the aim of enabling dermatologists to deliver evidence-based, high-value medical and surgical dermatologic care. The journal publishes a broad range of innovative studies and trials that shift research and clinical practice paradigms, expand the understanding of the burden of dermatologic diseases and key outcomes, improve the practice of dermatology, and ensure equitable care to all patients. It also features research and opinion examining ethical, moral, socioeconomic, educational, and political issues relevant to dermatologists, aiming to enable ongoing improvement to the workforce, scope of practice, and the training of future dermatologists. JAMA Dermatology aims to be a leader in developing initiatives to improve diversity, equity, and inclusion within the specialty and within dermatology medical publishing.

期刊最新文献

Human Papillomavirus Diversity in Asian Individuals With Cutaneous Squamous Cell Carcinoma. Necrobiosis Lipoidica. Risk of Skin Cancer Among Patients With Chronic Lymphocytic Leukemia. Predicting Laryngeal Involvement in Pemphigus Vulgaris Using a Clinical Risk Score. A Woman With Pulmonary Arterial Hypertension, Hemangiomas, and Hyperpigmentation.