An Open Label Study to Assess Efficacy of Oral Treprostinil Titrated to 3.0mg Three Times Daily or Highest Tolerable Dose in 30 Patients With Symptomatic Primary or Secondary Raynaud's Phenomenon Resistant to Standard Vasodilatory Therapy
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Change in the Raynaud's Condition Score from baseline (6-week run in), comparing treprostinil treatment phase vs. baseline phase.
研究概览
简要总结
Raynaud's phenomenon is a condition where the blood vessels in participants fingers and toes get too narrow when cold or stressed. This makes participants fingers and toes change colors - they might turn white, then blue, and finally red as blood flow returns. It can be painful and cause numbness or tingling.
When participants have Raynaud's, blood vessels react too strongly to cold or stress. Fingers and toes may turn white (blood moves away from the area), blue (lack of oxygen), or red and feel painful or tingly when warming up. These episodes usually last from a few minutes to several hours.
There are two types of Raynaud's. Primary Raynaud's (also called Raynaud's disease) itself and isn't connected to other health problems. It's the most common type and affects mostly women under 30. Secondary Raynaud's (also called Raynaud's phenomenon) is caused by other diseases like lupus, scleroderma, or rheumatoid arthritis. This type tends to be more serious and may cause painful sores on fingertips called digital ulcers.
For mild cases, staying warm might be enough. But if symptoms are severe, participants doctor might prescribe various medications including calcium channel blockers - blood pressure medicines that help open blood vessels, or other vasodilators - medicines that widen blood vessels. About 40% of people with scleroderma develop painful sores on their fingertips called digital ulcers. These happen when there isn't enough blood flow to heal small injuries.
For severe cases with digital ulcers, doctors might use prostacyclin therapy - medicines that mimic a natural substance that opens blood vessels. Oral treprostinil is a newer pill form of prostacyclin therapy that helps improve blood flow. The investigators are conducting a research study testing whether oral treprostinil - a pill that mimics prostacyclin (a natural blood vessel opener) - can help people with severe Raynaud's that doesn't respond to usual treatments. This represents hope for better treatment options for people with the most challenging cases of this condition.
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
- •Patients aged ≥ 18 years
- •Active Raynaud's Phenomenon defined as patients with refractory RP having four or more RP attacks per week in the 4 weeks before inclusion in the study.
- •Patients with either:
- •Primary Raynaud's Phenomenon
- •Patients with Raynaud's secondary to connective tissue diseases (including scleroderma (SSc), limited scleroderma (CREST), mixed connective tissue disease (MCTD), primary Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), with diagnosis of the underlying rheumatic disease based on standard criteria.
- •If patients are on phosphodiesterase inhibitors (sildenafil, tadalafil or vardenafil), endothelin antagonists, alpha adrenergic antagonists, or calcium channel blockers, their dose must be stable, defined as 3-months with no change in dose or frequency.
- •If female of childbearing potential (FOCP), has demonstrated a negative beta HCG (human chorionic gonadotropin) serum pregnancy test, and agrees to comply with any applicable contraceptive requirements of the protocol
- •If female of non-childbearing potential, meets either of the following criteria:
- •Is in a postmenopausal state defined as no menses for 12 months without an alternative medical cause and follicle-stimulating hormone (FSH) level consistent with postmenopause (>25 mIU/mL). If a participant is >60 years old and has been amenorrheic for >5 years, the participant may be enrolled with an FSH <25 mIU/mL after discussion with the PI.
- •Has a documented hysterectomy, bilaterial oophorectomy, or salpingectomy.
排除标准
- •Uncontrolled hypertension, diabetes mellitus, acute coronary or cerebrovascular event within 3 months, history of sympathectomy
- •Smoking within 3 months or smoking cessation using nicotine products
- •History of alcohol or other substance abuse within the previous year
- •Subjects with diverticulosis confirmed via endoscopic evaluation of the sigmoid colon with at least three diverticula noted
- •Subjects with moderate to severe liver disease, Child Pugh Class B or C
- •Subjects currently taking any other prostacyclin.
- •Pregnant or breast feeding or considering pregnancy in next 4 months
- •Was dosed in any clinical research study evaluating another investigational drug (including biologics) or therapy (including specific immunotherapy) within 30 days or 5 half-lives (whichever is longer) of an investigational biologic drug before the start of the screening period.
- •Any serious chronic, and/or unstable pre-existing medical, surgical, psychiatric or other condition that could interfere with the participant's safety, obtaining informed consent, or compliance with study procedures per investigator's discretion.
- •Hospitalization for any indication within 7 days before the start of screening.
研究组 & 干预措施
An open label study to assess efficacy of oral treprostinil in patients with Raynaud's
A single center open label study to assess efficacy of oral treprostinil titrated to a tolerable goal dose of 3.0 mg three times per day (TID) in 30 patients with symptomatic primary or secondary Raynaud's phenomenon resistant to standard vasodilatory therapy. Eligible subjects at the time of signing an informed consent will have a diagnosis of primary or secondary Raynaud's phenomenon. Once enrolled, subjects will enter a run in period and record each day for 42 days the number of RP attacks as well as the duration of each RP attack. Frequency and duration of RP recorded within 6-weeks before active treatment phase will be baseline data. After the run in period subjects will be titrated as tolerated to a goal dose of 3mg TID over a 6-week period. Throughout the study (6-week titration - 26-week treatment phase) subjects will record each day the number of RP attacks as well as the duration of each RP attack.
干预措施: Oral treprostinil (UT-15C) sustained release tablets (Drug)
结局指标
主要结局
Change in the Raynaud's Condition Score from baseline (6-week run in), comparing treprostinil treatment phase vs. baseline phase.
时间窗: 38 weeks
Once enrolled, throughout the study (6-weeks before active treatment; 6-week titration; 26-week treatment phase) subjects will record each day the number of RP attacks as well as the duration of each RP attack.. Frequency and duration of RP recorded within 6-weeks before active treatment phase will be considered to be baseline data. Every day subjects will complete the Raynaud's Condition Score (RCS). The RCS is an 11-point numerical rating scale (0-10) where 0 = "no difficulty" and 10 = "extreme difficulty". Patients complete the scale daily, and the average scores are calculated. The scale asks patients to consider multiple factors when rating their difficulty, including the number and duration of Raynaud's attacks, symptoms such as pain, numbness, burning, and tingling, and how the condition affects their ability to use their hands and perform daily activities.
次要结局
- Digital Ulcer Score(32 Weeks)
研究者
Aaron Waxman MD PhD
Executive Director, Center for Pulmonary Heart Diseases, Director, Pulmonary Vascular Disease Program
Brigham and Women's Hospital