A Phase II, Double-blind, Randomized, Placebo-controlled Study to Investigate Pharmacokinetics (PK), Safety and Efficacy of Intravenous Factor XIII Treatment in Patients With Systemic Sclerosis
试验速览
- 阶段
- 2 期
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Primary outcome assessed by skin involvement measured with modified Rodnan skin score
研究概览
简要总结
Many patients with Scleroderma (Systemic sclerosis) experience damage to blood vessels, mainly to the small arteries. A common manifestation of this is Raynaud's phenomenon (fingers or toes turning white then blue in the cold) and digital ulcers (open sores on the fingertips). The purpose of this study is to see how effective the study drug Human Factor XIII Concentrate is in treating patients who have these and other common manifestation of Scleroderma. It will be given in addition to the accepted treatments used for this disease.
详细描述
This is a phase II, double-blind, randomized, placebo-controlled study to investigate pharmacokinetics (PK), safety and efficacy of intravenous factor XIII treatment in patients with systemic sclerosis.
Scleroderma (Systemic sclerosis) is a multisystem rheumatic disease that is characterised by progressive vascular damage e.g Raynaud's phenomenon and digital ulcers and organ fibrosis e.g. skin thickening and pulmonary fibrosis.The disease is associated with significant morbidity and mortality and current therapeutic options are only partially effective, including Cyclophosphamide for skin or lung fibrosis and Bosentan which reduces but does not heal digital ulcers.
There is no cure available and there is therefore a high need for new therapeutic options.Administration of human Factor XIII (FXIII) concentrate in patients with scleroderma demonstrated promising results in the 1980s and 1990s . However these studies were not performed according to current Good Clinical Practice (GCP) guidelines and involved relatively small sample sizes.
This is a single site study, therefore all study participants will be seen at the Royal Free London National Health Service (NHS) Foundation Trust.Total study duration is 36 months and will involve 2 phases: an initial single dose, pharmacokinetic (PK) phase in 8 subjects over 6 weeks and a multiple dose, active treatment phase in 18 subjects over 24 weeks. During the treatment phase subjects will be randomized at 2:1 ratio to either FXIII or Placebo and will receive biweekly injection of either factor XIII Concentrate or placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
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 adults.
- •Subjects with a diagnosis of systemic sclerosis (scleroderma, SSc) according to the 2013 American College of Rheumatology European League Against Rheumatism (ACR EULAR) classification criteria. They will be classified according to LeRoy criteria as limited or diffuse subset.
- •Females of childbearing potential must be willing to use a reliable form of medically acceptable contraception and have a negative pregnancy test.
- •Subjects will have serological status for hepatitis A and B assessed at screening.
- •Patients who have given their free and informed consent. -≥ 18 years.
排除标准
- •Participants must:
- •Be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 6 weeks after treatment discontinuation (females of childbearing potential and males)
- •Have a negative pregnancy test within 7 days prior to being registered for trial treatment (females of childbearing potential). NOTE: Subjects are considered not of child bearing potential if they are surgically sterile (i.e. they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
- •Not be breastfeeding (females).
- •Participants must not:
- •Have allergies to excipients of the investigational medicinal product (IMP) and placebo
- •Have uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure ≥ 160 mmHg or sitting diastolic blood pressure ≥ 100 mmHg.
- •Have portal hypertension or chronic liver disease defined as mild to severe hepatic impairment (Child-Pugh Class A-C). Subjects positive for Hepatitis C with evidence of active viral replication on sensitive polymerase chain reaction (PCR) testing are also excluded.
- •Have hepatic dysfunction, defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≥ 3 times the upper limit of the normal range (× ULN) at the Screening Visit.
- •Have chronic renal insufficiency as defined by a serum creatinine ≥ 2.5 mg/dL (≤ 221 micromol/L) or requires dialysis.
- •Have a haemoglobin concentration ≤ 10 g/dL (≤ 100 g/L) at the Screening Visit.
- •Have a history of left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following: aortic or mitral valve disease (stenosis or regurgitation) defined as more than minimum aortic insufficiency and more than moderate mitral regurgitation (stenosis or regurgitation≥ grade 1); pericardial constriction; restrictive or congestive cardiomyopathy; left ventricular ejection fraction ≤ 40 % by multiple gated acquisition scan (MUGA), angiography, or echocardiography; left ventricular shortening fraction ≤ 22 % by echocardiography; or symptomatic coronary disease with demonstrable ischemia.
- •Have a history of malignancies within 5 years of Screening Visit with the exception of localized skin or cervical carcinomas.
- •Have psychiatric, addictive, or other disorder that compromises the ability to give informed consent for participating in this study. This includes subjects with a recent history of abusing alcohol or illicit drugs.
- •Be receiving ongoing treatment with hyperbaric oxygen
- •Have pulmonary artery hypertension (PAH)
- •Have received IV Iloprost within the last 2 months
- •Have been treated with sympathectomy or toxin botulinum A within the last 3 months
- •Have had thrombosis, stroke, pulmonary embolism or myocardial infarction in the last 6 months
- •Have a diagnosis of diabetes mellitus requiring dietary restriction of carbohydrate.
- •Be on a low sodium diet on medical advice.
- •Be participating in another clinical trial involving an investigational medicinal product.
研究组 & 干预措施
Active treatment arm
Fibrogammin®P, coagulation factor XIII concentrate (Human) IV infusion
干预措施: Fibrogammin®P, coagulation factor XIII concentrate (Human) (Drug)
Placebo arm
Placebo will be 0.9 % Sodium chloride solution IV infusion
干预措施: 0.9% sodium chloride (Drug)
结局指标
主要结局
Primary outcome assessed by skin involvement measured with modified Rodnan skin score
时间窗: 24 weeks
Primary outcome assessed by skin involvement measured with Raynaud condition score
时间窗: 24 weeks
次要结局
- Pulmonary function measured by pulmonary function test(24 weeks)
- Hand function measured with Cochin hand function(24 weeks)
- Quality of life measured with Short Form-36 (SF-36) quality of life questionnaire(24 weeks)
- Number of new digital ulcers (DU)(24 weeks)
- Digital ulcer worsening: Digital ulcer infection(24 weeks)
- Digital ulcer worsening: Gangrene(24 weeks)
- Complete healing of digital ulcers (DU)(24 weeks)
- Digital ulcer pain assessment(24 weeks)
- Digital ulcer worsening: hospitalisation required(24 weeks)
- Digital ulcer worsening: surgical intervention required(24 weeks)
- Digital ulcer worsening: Amputation(24 weeks)
- Digital ulcer worsening: Need of local sympathectomy(24 weeks)
- Digital ulcer worsening: Need of toxin Botulinum A(24 weeks)
- Digital ulcer worsening: Need of oral or parenteral antibiotic(24 weeks)
- Digital ulcer worsening: Need of intravenous (IV) Iloprost : this is considered treatment failure(24 weeks)