Open Label Treprostinil Raynaud's Study

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Oral treprostinil (UT-15C) sustained release tablets
  30 patients with symptomatic primary or secondary Raynaud's phenomenon (RP) resistant to standard vasodilatory therapy will be enrolled. Prior to treatment, subjects will record each day for 42 days the number of RP attacks as well as the duration of each RP attack, considered to be baseline data. After the 6-week baseline run in, all subjects will receive oral treprostinil sustained release tablets. Dose escalations can occur every 48 hours in 0.125 mg increments. Subjects will be titrated as t

Первичные конечные точки

• Change in the Raynaud's Condition Score from baseline (6-week run in), comparing treprostinil treatment phase vs. baseline phase. [Срок оценки: 38 weeks]

Вторичные конечные точки (1)

• Digital Ulcer Score [Срок оценки: 32 Weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Brigham and Women's Hospital — Boston
• Brigham and Women's Hospital — Boston

Публикации

• Maverakis E, Patel F, Kronenberg DG, Chung L, Fiorentino D, Allanore Y, Guiducci S, Hesselstrand R, Hummers LK, Duong C, Kahaleh B, Macgregor A, Matucci-Cerinic M, Wollheim FA, Mayes MD, Gershwin ME. International consensus criteria for the diagnosis of Raynaud's phenomenon. J Autoimmun. 2014 Feb-Mar;48-49:60-5. doi: 10.1016/j.jaut.2014.01.020. Epub 2014 Feb 1. PMID 24491823
• Shah AA, Schiopu E, Hummers LK, Wade M, Phillips K, Anderson C, Wise R, Boin F, Seibold JR, Wigley F, Rollins KD. Open label study of escalating doses of oral treprostinil diethanolamine in patients with systemic sclerosis and digital ischemia: pharmacokinetics and correlation with digital perfusion. Arthritis Res Ther. 2013 Apr 18;15(2):R54. doi: 10.1186/ar4216. PMID 23597147
• Milio G, Corrado E, Genova C, Amato C, Raimondi F, Almasio PL, Novo S. Iloprost treatment in patients with Raynaud's phenomenon secondary to systemic sclerosis and the quality of life: a new therapeutic protocol. Rheumatology (Oxford). 2006 Aug;45(8):999-1004. doi: 10.1093/rheumatology/kel038. Epub 2006 Feb 16. PMID 16484290
• Roustit M, Blaise S, Allanore Y, Carpentier PH, Caglayan E, Cracowski JL. Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud's phenomenon: systematic review and meta-analysis of randomised trials. Ann Rheum Dis. 2013 Oct;72(10):1696-9. doi: 10.1136/annrheumdis-2012-202836. Epub 2013 Feb 20. PMID 23426043
• Denton CP, Hachulla E, Riemekasten G, Schwarting A, Frenoux JM, Frey A, Le Brun FO, Herrick AL; Raynaud Study Investigators. Efficacy and Safety of Selexipag in Adults With Raynaud's Phenomenon Secondary to Systemic Sclerosis: A Randomized, Placebo-Controlled, Phase II Study. Arthritis Rheumatol. 2017 Dec;69(12):2370-2379. doi: 10.1002/art.40242. PMID 29193819
• Garcia de la Pena Lefebvre P, Nishishinya MB, Pereda CA, Loza E, Sifuentes Giraldo WA, Roman Ivorra JA, Carreira P, Rua-Figueroa I, Pego-Reigosa JM, Munoz-Fernandez S. Efficacy of Raynaud's phenomenon and digital ulcer pharmacological treatment in systemic sclerosis patients: a systematic literature review. Rheumatol Int. 2015 Sep;35(9):1447-59. doi: 10.1007/s00296-015-3241-1. Epub 2015 Apr 1. PMID 25824427
• Costa E, Cunha-Santos F, Dourado E, Oliveira D, Falzon L, Romao V, Duarte AC, Cordeiro A, Santiago T, Sepriano A. Systematic literature review to inform the Portuguese recommendations for the management of Raynaud's phenomenon and digital ulcers in systemic sclerosis and other connective tissue diseases. ARP Rheumatol. 2024 Jul 1;3(Apr-Jun):128-144. doi: 10.63032/YHBL8967. PMID 38306796
• Khouri C, Lepelley M, Bailly S, Blaise S, Herrick AL, Matucci-Cerinic M, Allanore Y, Trinquart L, Cracowski JL, Roustit M. Comparative efficacy and safety of treatments for secondary Raynaud's phenomenon: a systematic review and network meta-analysis of randomised trials. Lancet Rheumatol. 2019 Dec;1(4):e237-e246. doi: 10.1016/S2665-9913(19)30079-7. PMID 38229380

Идентификаторы

NCT: NCT07112183 · 2025P001219

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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