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A Therapeutic Open Label Study of Tocilizumab in the Treatment of Pulmonary Arterial Hypertension (TRANSFORM-UK)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02676947
Recruitment Status : Completed
First Posted : February 9, 2016
Last Update Posted : April 19, 2018
Sponsor:
Collaborators:
Roche Pharma AG
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Papworth Hospital NHS Foundation Trust

Brief Summary:
An open label study to assess the safety and efficacy of tocilizumab in group 1 pulmonary arterial hypertension patients

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Drug: Tocilizumab Phase 2

Detailed Description:

In Pulmonary Arterial Hypertension (PAH) raised blood pressure in the lungs leads to heart failure and early death. Patients not only have a significantly reduced life expectancy, but their quality of life is severely affected. If left untreated life expectancy is 2-3 years. Current treatments all aim to relax the vessels in the lung and lower the blood pressures, however none target the causes of the disease and currently there is not cure. Despite the availability of treatments the impact on mortality has been modest at best with one third of patients still dying within two years of diagnosis. There remains an urgent need to test new ways of treating PAH.

PAH is often associated with auto-immune diseases (when the bodies own system attacks itself rather than fight infection). Targeting components of the immune system involved in the development of disease offer a potential new area of treatment for PAH; an example known to be involved in the progression of PAH is the protein Interleukin-6 (IL-6). Tocilizumab is a drug which blocks the action of Interleukin-6 and blocking Interleukin-6 has been shown to be effective in animal models of PAH. Tocilizumab was demonstrated to be safe and effective in trials in other diseases associated with PAH, such as rheumatoid arthritis.

This study is a 6 month open label phase II trial of IV Tocilizumab in 21 patients with group 1 PAH. The aim of the trial is to see if Tocilizumab is safe and whether it reduces the blood pressure in the lungs. Patients will be given Tocilizumab intravenously once a month for six months with close safety monitoring. The trial will be led by Papworth Hospital and a total of 7 UK specialist centres will take part. The trial will assess the safety of the drug and response to treatment by measuring heart function, blood pressure in the lungs, exercise capacity and quality of life measurements.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Therapeutic Open Label Study of Tocilizumab in the Treatment of Pulmonary Arterial Hypertension
Study Start Date : January 2016
Actual Primary Completion Date : February 18, 2018
Actual Study Completion Date : February 18, 2018


Arm Intervention/treatment
Experimental: Open Label
Intravenous Tocilizumab 8mg/kg monthly (up to a maximum dose 800mg) for 6 months
Drug: Tocilizumab
Other Name: RoActemra




Primary Outcome Measures :
  1. Safety - Incidence and severity of adverse events [ Time Frame: 6 months ]
    Incidence and severity of treatment emergent adverse events

  2. Pulmonary vascular resistance- dynes (cm-5) [ Time Frame: Change from baseline pulmonary vascular resistance to end of study at 6 months ]
    Invasive haemodynamic assessment by right heart catheter


Secondary Outcome Measures :
  1. Six minute walk test [ Time Frame: Baseline and every month for 6 months ]
  2. N-Terminal pro-B-type Natriuretic Peptide [ Time Frame: Baseline and every month for 6 months ]
    Blood test - marker of cardiac function

  3. World Health Organisation functional class assessment of patient reported symptoms [ Time Frame: Baseline and every month for 6 months ]
    Assessment of pulmonary hypertension/heart failure symptoms and patient related daily living function.

  4. Quality of Life [ Time Frame: Baseline and every month for 6 months ]
    Disease specific questionnaire



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Group 1 PAH due to: Idiopathic or Heritable PAH, PAH associated with connective tissue disease excluding SLE, RA and mixed CTD, Drug and Toxins
  • WHO functional class II-IV
  • Weight more than 40kg
  • 6 minute walk distance of 100-500 m
  • Haemodynamic criteria measure by RHC
  • Documented negative V/Q scan or pulmonary arteriogram confirming absence of chromic thromboembolic disease
  • Resting oxygen saturations of >85%
  • Lung function confirming absence of significant lung disease
  • Stable on unchanged PAH therapeutic regime for at least 1 month

Exclusion Criteria:

  • Subjects on continuous infusions either intravenously or subcutaneously
  • Hypersensitivity to Investigational Product
  • Severe hepatic impairment
  • Severe renal impairment
  • Clinically significant anaemia
  • Blood platelets <100x10
  • Neutrophil count <2x10/L
  • Left ventricular disease/dysfunction risk factors
  • Myocardial infarction within 90 days prior to screening
  • Female subjects who are pregnant or breastfeeding
  • History of malignancies within past 5 years

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): NCT02676947


Locations
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United Kingdom
Papworth Hospital NHS Foundation Trust
Cambridge, Cambridgeshire, United Kingdom, CB23 3RE
Sponsors and Collaborators
Papworth Hospital NHS Foundation Trust
Roche Pharma AG
National Institute for Health Research, United Kingdom
Investigators
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Principal Investigator: Mark Toshner, MD Papworth Hospital NHS Foundation Trust
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Papworth Hospital NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT02676947    
Other Study ID Numbers: PO2060
First Posted: February 9, 2016    Key Record Dates
Last Update Posted: April 19, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Pulmonary Arterial Hypertension
Familial Primary Pulmonary Hypertension
Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases