临床试验/NCT04680975

NCT04680975终止2 期

A Phase 2, Open-label Multicenter Study to Evaluate the Efficacy and Safety of Belumosudil in Subjects With Diffuse Cutaneous Systemic Sclerosis (dcSSc)

Kadmon, a Sanofi Company6 个研究点分布在 1 个国家目标入组 10 人开始时间: 2021年3月3日最近更新: 2023年6月5日

适应症

干预措施

试验速览

阶段: 2 期
状态: 终止
发起方
入组人数: 10
试验地点: 6
主要终点: Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) Score at Week 24

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This was a phase 2, open-label, single-cohort, multicenter trial of belumosudil in participants with Diffuse Cutaneous Systemic Sclerosis (dcSSc). An estimated total of 12 to 15 participants would receive belumosudil 200 milligrams (mg) administered orally (PO) twice daily (BID) for 52 weeks. The primary analysis was at 24 weeks.

详细描述

The primary objective of this phase 2, open-label, single-cohort, multicenter trial was to evaluate the efficacy of belumosudil 200 mg BID using the Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) after 24 weeks of therapy. The duration of the study was approximately 14 months (4 weeks for screening, 52 weeks of dosing period, and 4 weeks of Follow-up)

Participants who had signed an Institutional Review Board/Independent Ethics Committee-(IRB/IEC)-approved informed consent form (ICF) and met all of the inclusion/exclusion criteria were enrolled. A total of 10 participants at 6 sites received belumosudil 200 mg in tablet form administered PO BID for 52 weeks. The total duration of the study is approximately 14 months: a 4-week screening period, a 52-week treatment period, and a 4-week follow-up.

The primary endpoint was analyzed using Week 24 data.

Efficacy was assessed throughout the 52-week dosing period using:

Composite Response Index in Systemic Sclerosis (CRISS)
Modified Rodnan Skin Score (mRSS)
Pulmonary Function Tests (PFTs)
Physician Global Assessment
Patient Global Assessment

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Male and female participants greater than or equal to (>=) 18 years old with the diagnosis of dcSSc according to the 2013 American College of Rheumatology and European League Against Rheumatism.
•Had disease duration (defined as interval from first non Raynaud disease manifestation) of less than or equal to (<=) 6 years.
•Had mRSS of >=15 but <=
•Had active disease as determined by the Principal Investigator within the 6 months prior to screening.
•Adequate organ and bone marrow functions evaluated during the 28 days prior to enrollment as follows:
•Absolute neutrophil count >= 1.5*10^9/L
•Platelet count >= 100*10^9/L
•Total bilirubin <= 1.0*upper limit of normal (ULN)
•Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and serum creatinine <= 1.5*ULN.
•Female participants of childbearing potential had a negative pregnancy test at screening. Females of childbearing potential were defined as sexually mature women without prior hysterectomy or who had any evidence of menses in the past 12 months. However, women who had been amenorrheic for 12 or more months were still considered to be of childbearing potential if the amenorrhea was possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression.
•Women of childbearing potential (i.e., menstruating women) must had a negative urine pregnancy test (positive urine tests were to be confirmed by serum test) documented within the 24-hour period prior to the first dose of study drug.
•Sexually active women of childbearing potential enrolled in the study agreed to use two forms of accepted methods of contraception during the course of the study and for 3 months after their last dose of study drug. Effective birth control includes (i) intrauterine device plus 1 barrier method; (ii) on stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus 1 barrier method; or (iii) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm), or a vasectomized partner.
•For male participants who were sexually active and who were partners of premenopausal women: agreement to use 2 forms of contraception as in criterion number 6b above during the treatment period and for at least 3 months after the last dose of study drug.
•Male participants must not donate sperm for 3 months after last dose of study drug.
•Able to provide written informed consent prior to the performance of any study-specific procedures.

排除标准

•Participants had corrected QT interval using Fridericia's formula (QTcF) greater than 450 milliseconds.
•Ongoing use or current use of concomitant medication known to have the potential for QTc prolongation.
•Female participant who was pregnant or breastfed.
•Participated in another study with an investigational drug within 28 days of study entry (for studies involving biologics, within 3 half-lives of the biologic).
•History or other evidence of severe illness or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study.
•Chronic heart failure with New York Heart Association Classes II, III, or IV.
•Acute or chronic liver disease (e.g., cirrhosis).
•Positive human immunodeficiency virus (HIV) test.
•Active hepatitis C virus (HCV), hepatitis B virus (HBV), or positive whole blood tuberculin test.
•Diagnosed with any malignancy within 3 years of enrollment, with the exception of basal cell or completely resected squamous cell carcinoma of the skin, resected in situ cervical malignancy, resected breast ductal carcinoma in situ, or low risk prostate cancer after curative resection.
•Had previous exposure to belumosudil or known allergy/sensitivity to belumosudil, or any other Rho-associated Protein Kinase-2 (ROCK2) inhibitor.
•Scleroderma renal crisis within 4 months prior to enrollment.
•Forced vital capacity <= 50% Predicted.

研究组 & 干预措施

Belumosudil

Experimental

Participants received belumosudil 200 mg tablet orally PO, BID for 52 weeks.

干预措施: Belumosudil (Drug)

结局指标

主要结局

Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) Score at Week 24

时间窗: Week 24

CRISS components included the following domains: modified Rodnan skin score (mRSS), forced vital capacity (FVC) percent predicted, physician global assessment, patient global assessment, and scleroderma health assessment questionnaire disability-index (SHAQ-DI). An algorithm determines the predicted probability of improvement from Baseline by incorporating change in the mRSS, FVC percent predicted, physician and patient global assessments, and SHAQ-DI. The outcome is a continuous variable between 0.0 and 1.0 (0 to 100%). A higher score indicated greater probability of improvement. Participants are not considered improved if they develop new onset of renal crisis, new onset or worsening of lung fibrosis, new onset of pulmonary arterial hypertension, new onset of left ventricular failure during the trial. CRISS score greater than 60% is considered the minimally important difference.

次要结局

Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) Score at Weeks 8, 16, 36, and 52(Week 8, 16, 36 and 52)
Change From Baseline in Scleroderma Health Assessment Questionnaire-Disability Index (SHAQ-DI) Total Score at Weeks 8, 16, 36, and 52(Baseline, Week 8, 16, 36 and 52)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(From first dose administration (i.e., Day 1) of study medication up to 28 days after last dose (i.e., up to 57.5 weeks))
Physician Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Week 24(Week 24)
Forced Vital Capacity (FVC) Level at Week 24(Week 24)
Scleroderma Health Assessment Questionnaire-Disability Index (SHAQ-DI) Total Score at Week 24(Week 24)
Change From Baseline in Modified Rodnan Skin Thickness Score (mRSS) at Weeks 8, 16, 36, and 52(Baseline, Week 8, 16, 36 and 52)
Change From Baseline in Forced Vital Capacity (FVC) Level at Weeks 8, 16, 36, and 52(Baseline, Week 8, 16, 36 and 52)
Change From Baseline in Physician Global Assessment (Reported by the Physician) Quantified of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Weeks 8, 16, 36, and 52(Baseline, Week 8, 16, 36 and 52)
Modified Rodnan Skin Score (mRSS) at Week 24(Week 24)
Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Week 24(Week 24)
Change From Baseline in Patient Global Assessment of Participant's Overall Health Using Visual Analogue Scale (VAS) Score at Weeks 8, 16, 36, and 52(Baseline, Week 8, 16, 36 and 52)

研究者

发起方

Kadmon, a Sanofi Company

申办方类型

Industry

责任方

Sponsor

研究点 (6)

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