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

Pulmonary Arterial Hypertension Clinical Trial

— TRANSFORM-UK  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02676947
• Other study ID #: PO2060
• Status: Completed
• Phase: Phase 2
• First received: December 21, 2015
• Last updated: April 17, 2018
• Start date: January 2016
• Est. completion date: February 18, 2018

Study information

• Verified date: April 2018
• Source: Papworth Hospital NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: February 18, 2018
• Est. primary completion date: February 18, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Tocilizumab

Locations

Country	Name	City	State
United Kingdom	Papworth Hospital NHS Foundation Trust	Cambridge	Cambridgeshire

Sponsors (3)

Lead Sponsor	Collaborator
Papworth Hospital NHS Foundation Trust	National Institute for Health Research, United Kingdom, Roche Pharma AG

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety - Incidence and severity of adverse events	Incidence and severity of treatment emergent adverse events	6 months
Primary	Pulmonary vascular resistance- dynes (cm-5)	Invasive haemodynamic assessment by right heart catheter	Change from baseline pulmonary vascular resistance to end of study at 6 months
Secondary	Six minute walk test		Baseline and every month for 6 months
Secondary	N-Terminal pro-B-type Natriuretic Peptide	Blood test - marker of cardiac function	Baseline and every month for 6 months
Secondary	World Health Organisation functional class assessment of patient reported symptoms	Assessment of pulmonary hypertension/heart failure symptoms and patient related daily living function.	Baseline and every month for 6 months
Secondary	Quality of Life	Disease specific questionnaire	Baseline and every month for 6 months