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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
26
IV infusion
IV infusion
Royal Free London NHS Foundation Trust
London, United Kingdom
RECRUITINGPrimary outcome assessed by skin involvement measured with modified Rodnan skin score
Time frame: 24 weeks
Primary outcome assessed by skin involvement measured with Raynaud condition score
Time frame: 24 weeks
Pulmonary function measured by pulmonary function test
Pulmonary function measured by pulmonary function test
Time frame: 24 weeks
Hand function measured with Cochin hand function
Hand function measured with Cochin hand function
Time frame: 24 weeks
Quality of life measured with Short Form-36 (SF-36) quality of life questionnaire
Quality of life measured with SF36 quality of life questionnaire
Time frame: 24 weeks
Number of new digital ulcers (DU)
Prevention of new DU: Number of new DU developed during a 24-week period of treatment
Time frame: 24 weeks
Complete healing of digital ulcers (DU)
Healing of DU: Complete healing of DUs present at baseline; each DU is considered as an entity
Time frame: 24 weeks
Digital ulcer pain assessment
DU Pain assessment at 4, 8, 12, 16, 24 weeks of treatment: Pain will be assessed by analogue scale for pain (Visual Analogue Scale, VAS)
Time frame: 24 weeks
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Digital ulcer pain assessment
DU Pain assessment at 4, 8, 12, 16, 24 weeks of treatment: Pain will be assessed by Raynaud's severity (Raynaud's condition score)
Time frame: 24 weeks
Digital ulcer worsening: hospitalisation required
Number of overnight hospitalisations for digital ulcers
Time frame: 24 weeks
Digital ulcer worsening: surgical intervention required
Number of additional surgical treatments for digital ulcer in outpatient clinic
Time frame: 24 weeks
Digital ulcer worsening: Digital ulcer infection
Number of digital ulcers with infections
Time frame: 24 weeks
Digital ulcer worsening: Gangrene
Number of episodes of gangrene
Time frame: 24 weeks
Digital ulcer worsening: Amputation
Number of amputations
Time frame: 24 weeks
Digital ulcer worsening: Need of local sympathectomy
Number of local sympathectomies
Time frame: 24 weeks
Digital ulcer worsening: Need of toxin Botulinum A
Number of treatments with Botulinum toxin A
Time frame: 24 weeks
Digital ulcer worsening: Need of oral or parenteral antibiotic
Number of treatments needed with oral or parenteral antibiotic
Time frame: 24 weeks
Digital ulcer worsening: Need of intravenous (IV) Iloprost : this is considered treatment failure
Number of treatments needed with intravenous (IV) Iloprost : this is considered treatment failure
Time frame: 24 weeks