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CSL Behring Sclero XIII

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ClinicalTrials.gov Identifier: NCT02551042
Recruitment Status : Unknown
Verified May 2016 by University College, London.
Recruitment status was:  Recruiting
First Posted : September 16, 2015
Last Update Posted : May 30, 2016
Sponsor:
Collaborator:
CSL Behring
Information provided by (Responsible Party):
University College, London

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Systemic Sclerosis Drug: Fibrogammin®P, coagulation factor XIII concentrate (Human) Drug: 0.9% sodium chloride Phase 2

Detailed Description:

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  (Clinical Trial)
Estimated Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : September 2015
Estimated Primary Completion Date : September 2016
Estimated Study Completion Date : September 2018


Arm Intervention/treatment
Experimental: Active treatment arm
Fibrogammin®P, coagulation factor XIII concentrate (Human) IV infusion
Drug: Fibrogammin®P, coagulation factor XIII concentrate (Human)
IV infusion
Other Name: Factor XIII

Placebo Comparator: Placebo arm
Placebo will be 0.9 % Sodium chloride solution IV infusion
Drug: 0.9% sodium chloride
IV infusion
Other Name: Normal saline




Primary Outcome Measures :
  1. Primary outcome assessed by skin involvement measured with modified Rodnan skin score [ Time Frame: 24 weeks ]
  2. Primary outcome assessed by skin involvement measured with Raynaud condition score [ Time Frame: 24 weeks ]

Secondary Outcome Measures :
  1. Pulmonary function measured by pulmonary function test [ Time Frame: 24 weeks ]
    Pulmonary function measured by pulmonary function test

  2. Hand function measured with Cochin hand function [ Time Frame: 24 weeks ]
    Hand function measured with Cochin hand function

  3. Quality of life measured with Short Form-36 (SF-36) quality of life questionnaire [ Time Frame: 24 weeks ]
    Quality of life measured with SF36 quality of life questionnaire

  4. Number of new digital ulcers (DU) [ Time Frame: 24 weeks ]
    Prevention of new DU: Number of new DU developed during a 24-week period of treatment

  5. Complete healing of digital ulcers (DU) [ Time Frame: 24 weeks ]
    Healing of DU: Complete healing of DUs present at baseline; each DU is considered as an entity

  6. Digital ulcer pain assessment [ Time Frame: 24 weeks ]
    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)

  7. Digital ulcer pain assessment [ Time Frame: 24 weeks ]
    DU Pain assessment at 4, 8, 12, 16, 24 weeks of treatment: Pain will be assessed by Raynaud's severity (Raynaud's condition score)

  8. Digital ulcer worsening: hospitalisation required [ Time Frame: 24 weeks ]
    Number of overnight hospitalisations for digital ulcers

  9. Digital ulcer worsening: surgical intervention required [ Time Frame: 24 weeks ]
    Number of additional surgical treatments for digital ulcer in outpatient clinic

  10. Digital ulcer worsening: Digital ulcer infection [ Time Frame: 24 weeks ]
    Number of digital ulcers with infections

  11. Digital ulcer worsening: Gangrene [ Time Frame: 24 weeks ]
    Number of episodes of gangrene

  12. Digital ulcer worsening: Amputation [ Time Frame: 24 weeks ]
    Number of amputations

  13. Digital ulcer worsening: Need of local sympathectomy [ Time Frame: 24 weeks ]
    Number of local sympathectomies

  14. Digital ulcer worsening: Need of toxin Botulinum A [ Time Frame: 24 weeks ]
    Number of treatments with Botulinum toxin A

  15. Digital ulcer worsening: Need of oral or parenteral antibiotic [ Time Frame: 24 weeks ]
    Number of treatments needed with oral or parenteral antibiotic

  16. Digital ulcer worsening: Need of intravenous (IV) Iloprost : this is considered treatment failure [ Time Frame: 24 weeks ]
    Number of treatments needed with intravenous (IV) Iloprost : this is considered treatment failure


Other Outcome Measures:
  1. Safety endpoints: Physical examination (including height, weight, BMI, digital ulcer characterization) [ Time Frame: 24 weeks ]
    Physical examination (including height, weight, BMI, digital ulcer characterization)

  2. Safety endpoints: Adverse events [ Time Frame: 24 weeks ]
    Adverse events

  3. Safety endpoints: Serious adverse events [ Time Frame: 24 weeks ]
    Serious adverse events

  4. Safety endpoints: ECG [ Time Frame: 24 weeks ]
    ECG

  5. Safety endpoints: Vital signs [ Time Frame: 24 weeks ]
    Vital signs

  6. Safety endpoints: Clinical laboratory parameters [ Time Frame: 24 weeks ]
    Clinical laboratory parameters

  7. Safety endpoints: Pregnancy [ Time Frame: 24 weeks ]
    Serum or urine pregnancy tests will be performed at each visit and will be reported positive or negative

  8. Safety endpoints -Adverse events of special interest: thromboembolic events [ Time Frame: 24 weeks ]
    Adverse events of special interest: thromboembolic events



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02551042


Contacts
Contact: Christopher Denton, PhD 02073177544 c.denton@ucl.ac.uk
Contact: Rachel Ochiel 02073177544 rachel.ochiel@nhs.net

Locations
United Kingdom
Royal Free London NHS Foundation Trust Recruiting
London, United Kingdom, NW3 2QG
Sponsors and Collaborators
University College, London
CSL Behring
Investigators
Principal Investigator: Christopher Denton, PhD Royal Free London NHS Foundation Trust

Additional Information:
Publications:

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT02551042     History of Changes
Other Study ID Numbers: 13/0417
2014-001101-40 ( EudraCT Number )
First Posted: September 16, 2015    Key Record Dates
Last Update Posted: May 30, 2016
Last Verified: May 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by University College, London:
Digital Ulcers
Raynauds Phenomenon
Factor XIII

Additional relevant MeSH terms:
Sclerosis
Scleroderma, Systemic
Scleroderma, Diffuse
Pathologic Processes
Connective Tissue Diseases
Skin Diseases