A Therapeutic Open Label Study of Tocilizumab in the Treatment of Pulmonary Arterial Hypertension

Overview

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 18, 2018

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.

Interventions

  • Drug: Tocilizumab

Arms, Groups and Cohorts

  • Experimental: Open Label
    • Intravenous Tocilizumab 8mg/kg monthly (up to a maximum dose 800mg) for 6 months

Clinical Trial Outcome Measures

Primary Measures

  • Safety – Incidence and severity of adverse events
    • Time Frame: 6 months
    • Incidence and severity of treatment emergent adverse events
  • 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 Measures

  • Six minute walk test
    • Time Frame: Baseline and every month for 6 months
  • N-Terminal pro-B-type Natriuretic Peptide
    • Time Frame: Baseline and every month for 6 months
    • Blood test – marker of cardiac function
  • 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.
  • Quality of Life
    • Time Frame: Baseline and every month for 6 months
    • Disease specific questionnaire

Participating in This Clinical Trial

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 <100×10 – Neutrophil count <2×10/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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Papworth Hospital NHS Foundation Trust
  • Collaborator
    • Roche Pharma AG
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Mark Toshner, MD, Principal Investigator, Papworth Hospital NHS Foundation Trust

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.