Pulmonary Arterial HypertensionPhase 2TRANSFORM-UKNCT02676947
A Therapeutic Open Label Study of Tocilizumab in the Treatment of Pulmonary Arterial Hypertension
A Phase 2 study testing Tocilizumab in people with Pulmonary Arterial Hypertension, run by Papworth Hospital NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
An open label study to assess the safety and efficacy of tocilizumab in group 1 pulmonary arterial hypertension patients Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Tocilizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2016to 18 Feb 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- Resting oxygen saturations of >85%
- Lung function confirming absence of significant lung disease
- Stable on unchanged PAH therapeutic regime for at least 1 month
Who cannot join
- Subjects on continuous infusions either intravenously or subcutaneously
- Hypersensitivity to Investigational Product
- Severe hepatic impairment
- Severe renal impairment
- Clinically significant anaemia
- Blood platelets <100x10
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Papworth Hospital NHS Foundation Trust
Cambridge, Cambridgeshire, CB23 3RE
About this study
An open label study to assess the safety and efficacy of tocilizumab in group 1 pulmonary arterial hypertension patients
Read the 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.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Tocilizumab
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
Also called RoActemra
| Study group | Role | What they receive |
|---|---|---|
| Open Label | Experimental | Intravenous Tocilizumab 8mg/kg monthly (up to a maximum dose 800mg) for 6 months Receives: Drug: Tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety - Incidence and severity of adverse events
Incidence and severity of treatment emergent adverse events
Measured: 6 months
Pulmonary vascular resistance- dynes (cm-5)
Invasive haemodynamic assessment by right heart catheter
Measured: Change from baseline pulmonary vascular resistance to end of study at 6 months
Secondary outcomes (4)
Six minute walk test
Measured: Baseline and every month for 6 months
N-Terminal pro-B-type Natriuretic Peptide
Blood test - marker of cardiac function
Measured: Baseline and every month for 6 months
World Health Organisation functional class assessment of patient reported symptoms
Assessment of pulmonary hypertension/heart failure symptoms and patient related daily living function.
Measured: Baseline and every month for 6 months
Quality of Life
Disease specific questionnaire
Measured: Baseline and every month for 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2016 (estimated)
- Study startJan 2016
- Primary completion18 Feb 2018
- Study completion18 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Papworth Hospital NHS Foundation Trust
- Sponsor type
- Other government
- Collaborators
- Roche Pharma AG, National Institute for Health Research, United Kingdom
- Responsible party
- Sponsor
- Investigators
- Mark Toshner, MD, Principal investigator, Papworth Hospital NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02676947
- Sponsor's protocol ID
- PO2060
- Acronym
- TRANSFORM-UK
- Status last verified
- Apr 2018
- First submitted
- 21 Dec 2015
- Last updated
- 19 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Toshner M, Church C, Harbaum L, Rhodes C, Villar Moreschi SS, Liley J, Jones R, Arora A, Batai K, Desai AA, Coghlan JG, Gibbs JSR, Gor D, Graf S, Harlow L, Hernandez-Sanchez J, Howard LS, Humbert M, Karnes J, Kiely DG, Kittles R, Knightbridge E, Lam B, Lutz KA, Nichols WC, Pauciulo MW, Pepke-Zaba J, Suntharalingam J, Soubrier F, Trembath RC, Schwantes-An TL, Wort SJ, Wilkins MR, Gaine S, Morrell NW, Corris PA; Uniphy Clinical Trials Network. Mendelian randomisation and experimental medicine approaches to interleukin-6 as a drug target in pulmonary arterial hypertension. Eur Respir J. 2022 Mar 10;59(3):2002463. doi: 10.1183/13993003.02463-2020. Print 2022 Mar.
PubMed 34588193
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Therapeutic Open Label Study of Tocilizumab in the Treatment of Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT02676947
- Acronym / sponsor ID
- TRANSFORM-UK / PO2060
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Papworth Hospital NHS Foundation TrustOther government
- Collaborators
- Roche Pharma AG, National Institute for Health Research, United Kingdom
- Study start
- Jan 2016
- Primary completion
- 18 Feb 2018 (actual)
- Study completion
- 18 Feb 2018 (actual)
- First posted
- 9 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An open label study to assess the safety and efficacy of tocilizumab in group 1 pulmonary arterial hypertension patients
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open Label | Experimental | Drug: TocilizumabIntravenous Tocilizumab 8mg/kg monthly (up to a maximum dose 800mg) for 6 months |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (11 listed)
- Subjects on continuous infusions either intravenously or subcutaneously
- Hypersensitivity to Investigational Product
- Severe hepatic impairment
- Severe renal impairment
- Clinically significant anaemia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TocilizumabAlso: RoActemra | Drug | Open Label |
Primary outcome
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
4 secondary outcomes
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
World Health Organisation functional class assessment of patient reported symptoms
Time frame: Baseline and every month for 6 months
Quality of Life
Time frame: Baseline and every month for 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2018.
- Derived from this study: PubMed 34588193Toshner M, Church C, Harbaum L, Rhodes C, Villar Moreschi SS, Liley J, Jones R, Arora A, Batai K, Desai AA, Coghlan JG, Gibbs JSR, Gor D, Graf S, Harlow L, Hernandez-Sanchez J, Howard LS, Humbert M, Karnes J, Kiely DG, Kittles R, Knightbridge E, Lam B, Lutz KA, Nichols WC, Pauciulo MW, Pepke-Zaba J, Suntharalingam J, Soubrier F, Trembath RC, Schwantes-An TL, Wort SJ, Wilkins MR, Gaine S, Morrell NW, Corris PA; Uniphy Clinical Trials Network. Mendelian randomisation and experimental medicine approaches to interleukin-6 as a drug target in pulmonary arterial hypertension. Eur Respir J. 2022 Mar 10;59(3):2002463. doi: 10.1183/13993003.02463-2020. Print 2022 Mar.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Toshner, MD principal investigator
Papworth Hospital NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tocilizumab in people with Pulmonary Arterial Hypertension, run by Papworth Hospital NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety - Incidence and severity of adverse events (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02676947, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2018.