Bhatia Neal, Del Rosso James, Stein Gold Linda, Lain Edward, Draelos Zoe Diana, Sidgiddi Srinivas
Therapeutics Clinical Research, San Diego, California.
JDR Dermatology Research, Las Vegas, Nevada.
JAMA Dermatol. 2025 May 1;161(5):499-507. doi: 10.1001/jamadermatol.2024.6542.
A low-dose modified formulation of minocycline hydrochloride, DFD-29, is under evaluation for treating papulopustular rosacea (PPR).
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.
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.
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.
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.
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.
ClinicalTrials.gov Identifiers: NCT05296629 and NCT05343455.
低剂量改良型盐酸米诺环素制剂DFD-29正在接受治疗丘疹脓疱型玫瑰痤疮（PPR）的评估。
确定40毫克DFD-29与40毫克多西环素及安慰剂治疗PPR的疗效和安全性。
设计、地点和参与者：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。纳入了年龄在18岁及以上的中度至重度PPR健康成年人。
参与者按3:3:2随机分组，分别口服40毫克DFD-29（盐酸米诺环素胶囊）、40毫克多西环素或安慰剂，每日1次，共16周。
共同主要疗效结局为：（1）DFD-29与安慰剂相比，达到研究者整体评估（IGA）治疗成功的参与者比例；（2）DFD-29与安慰剂相比，总炎性皮损计数的减少情况。次要结局包括DFD-29与多西环素在共同主要结局方面的比较，以及DFD-29与安慰剂在红斑减轻方面的比较。
在653名纳入的参与者中，323人在MVOR-1中随机分组（247名[76.5%]女性；平均[标准差]年龄，47.2[13.7]岁），330人在MVOR-2中随机分组（249名[75.5%]女性；平均[标准差]年龄，51.6[14.0]岁）。与安慰剂相比，DFD-29在IGA成功率方面显示出更高的疗效（MVOR-1：治疗差异[TD]，32.9%；95%置信区间，19.6 - 46.2；P < .001；MVOR-2：TD，34.1%；95%置信区间，21.3 - 46.8；P < .001），与多西环素相比也更高（MVOR-1：TD，18.0%；95%置信区间，5.0 - 31.1；P = .01；MVOR-2：TD，28.3%；95%置信区间，17.4 - 39.3；P < .001）。与安慰剂相比，DFD-29在总炎性皮损的最小二乘均值减少方面也显示出更高的疗效（MVOR-1：TD，-9.2；95%置信区间，-11.5至-6.9；P < .001；MVOR-2：TD，-6.8；95%置信区间，-8.9至-4.8；P < .001），与多西环素相比同样如此（MVOR-1：TD，-4.7；95%置信区间，-6.7至-2.8；P < .001；MVOR-2：TD，-3.5；95%置信区间，-5.4至-1.6；P < .001）。在MVOR-1中，DFD-29、多西环素和安慰剂的不良事件报告率分别为121例中的32例（26.4%）、116例中的25例（21.6%）和76例中的27例（35.5%），在MVOR-2中分别为122例中的51例（41.8%）、121例中的40例（33.1%）和82例中的30例（36.6%）。DFD-29、多西环素和安慰剂最常见的不良事件是鼻咽炎，在MVOR-1中分别为121例中的4例（3.3%）、116例中的2例（1.7%）和76例中的3例（3.9%），在MVOR-2中分别为122例中的13例（10.7%）、121例中的10例（8.3%）和82例中的13例（15.9%），以及COVID-19，在MVOR-1中分别为121例中的4例（3.3%）、116例中的3例（2.6%）和76例中的4例（5.3%） 在MVOR-2中分别为122例中的7例（5.7%）、121例中的8例（6.6%）和82例中的5例（6.1%）。
在本研究中，DFD-29在疗效上优于多西环素和安慰剂，在治疗PPR方面显示出良好的风险效益比。
ClinicalTrials.gov标识符：NCT05296629和NCT05343455。
