Clinical Trial Results:
Optimising Treatment With Tumour Necrosis Factor Inhibitors In Rheumatoid Arthritis: Is Dose Tapering Practical In Good Responders? A “Proof Of Principle” And Exploratory Trial. (OPTTIRA)
Summary
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EudraCT number |
2010-020738-24 |
Trial protocol |
GB |
Global end of trial date |
07 Jul 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Mar 2019
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First version publication date |
15 Mar 2019
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Other versions |
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Summary report(s) |
Summary Report |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
Version 1.2 (20/06/2011)
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Additional study identifiers
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ISRCTN number |
ISRCTN28955701 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
King's College London
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Sponsor organisation address |
The Strand, London, United Kingdom, WC2R 2LS
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Public contact |
Professor David Scott, King's College London, +44 02078485200, kch-tr.opttira@nhs.net
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Scientific contact |
Professor David Scott, King's College London, +44 02078485200, kch-tr.opttira@nhs.net
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
07 Jul 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
07 Jul 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Jul 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The study investigates whether in it is possible to reduce the dose of or even stop TNF-inhibitors without adversely affecting the control of this disease. This will be assessed by looking at:
a. The risk of disease flares (using the disease activity score with a 28 tender and swollen joint count (DAS28). An increase of disease activity score (DAS28) of 0.6 or more represents adversely affecting disease control and is considered a flare)
b. If flares are reversed by reverting to the original TNF inhibitor dosage
c. If either tapering group show worse key RA assessments including disease activity (DAS28) and disability as measured by health assessment questionnaire (HAQ) scores
d. Structural damage (plain hand and fe
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Protection of trial subjects |
Participants had their DMARD monitoring performed as part of the trial’s safety monitoring which has been designed to fit with routine clinical practice,
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Background therapy |
Patients will continue to receive the DMARDs prescribed prior to trial entry at standard doses . They will be taking either Etanercept OR Adalimumab | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Apr 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 97
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Worldwide total number of subjects |
97
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EEA total number of subjects |
97
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
97
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were recruited from multiple centers across the UK between 2011 and 2014 | ||||||||||||
Pre-assignment
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Screening details |
Patients already on TNF inhibitors (failure to respond to two DMARDs) and have a sustained good response. Patients must be taking Etanercept or Adalimumab at standard doses (50mg/week and 40mg/fortnight respectively) and at least one concomit | ||||||||||||
Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||
Blinding implementation details |
Not applicable
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Group 1 - TNF inhibitor tapered to 66% of initial dose | ||||||||||||
Arm description |
Experimental group 1 – patients have their TNF inhibitor tapered to 66% of initial dose by reducing frequency of dosing. Month 1 to 6 - TNF inhibitor tapered to 66% of initial dose. Month 7 to 12 - Time between injections increased on each occasion until injections are stopped completely. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Etanercept
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
50mg subcutaneously reducing as detailed in trial protocol.
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Investigational medicinal product name |
Adalimumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
During the “Proof of Principle” phase (months 0 – 6) patients will self administer Adalimumab subcutaneously at a dose of 40mg according to the protocol regime.
During the Exploratory Phase (months 7 - 12) patients in the experimental groups will increase the time between injections until injections are stopped completely
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Arm title
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Group 2 - TNF inhibitor tapered to 33% | ||||||||||||
Arm description |
Experimental group 2 - patients have their TNF inhibitor tapered to 33% of initial dose. Months 1 to 6 - patients have their TNF inhibitor tapered to 33% of initial dose. Months 7 to 12 - During the Exploratory Phase (months 7 - 12) patients in the experimental groups will increase the time between injections on each occasion until injections are stopped completely. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Etanercept
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
50mg subcutaneously reducing as detailed in trial protocol. reducing to 33% of original dose.
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Investigational medicinal product name |
Adalimumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
During the “Proof of Principle” phase (months 0 – 6) patients will self administer Adalimumab subcutaneously at a dose of 40mg according to the protocol regime.
During the Exploratory Phase (months 7 - 12) patients in the experimental groups will increase the time between injections until injections are stopped completely
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Arm title
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Group 3 Control Group | ||||||||||||
Arm description |
Control group – patients continue on standard doses as prescribed prior to trial entry. | ||||||||||||
Arm type |
Control | ||||||||||||
Investigational medicinal product name |
Etanercept
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
50mg subcutaneously weekly as routine standard of care.
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Investigational medicinal product name |
Adalimumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Adalimumab subcutaneously at a dose of 40mg as per routine standard of care.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Group 1 - TNF inhibitor tapered to 66% of initial dose
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Reporting group description |
Experimental group 1 – patients have their TNF inhibitor tapered to 66% of initial dose by reducing frequency of dosing. Month 1 to 6 - TNF inhibitor tapered to 66% of initial dose. Month 7 to 12 - Time between injections increased on each occasion until injections are stopped completely. | ||
Reporting group title |
Group 2 - TNF inhibitor tapered to 33%
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Reporting group description |
Experimental group 2 - patients have their TNF inhibitor tapered to 33% of initial dose. Months 1 to 6 - patients have their TNF inhibitor tapered to 33% of initial dose. Months 7 to 12 - During the Exploratory Phase (months 7 - 12) patients in the experimental groups will increase the time between injections on each occasion until injections are stopped completely. | ||
Reporting group title |
Group 3 Control Group
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Reporting group description |
Control group – patients continue on standard doses as prescribed prior to trial entry. |
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End point title |
Development of flares [1] | ||||||||||||
End point description |
Development of flares, defined as an increase in DAS28 scores ≥ 0.6 [44].
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End point type |
Primary
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End point timeframe |
0 to 12 months
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: See attached chart for results |
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Attachments |
Secondary Outcomes Flare Rates Adverse Event Data |
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No statistical analyses for this end point |
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End point title |
Secondary Outcome measures | ||||||||||||
End point description |
DAS28 (tender and swollen joint counts, patient global (VAS), ESR) and Extended Joint Count 68/66
Simple disease activity score (SDAI) and clinical disease activity score (CDAI) [45]
Health Assessment Questionnaire (HAQ) scores [46]
Adverse events
EuroQol scores [47]
SF-36
Plain x-rays of the hands and feet scored by Larsen’s and van der Heijdi Sharpe Modified Scores (to provide preliminary data)
Analysis of serum, immunological and gene expression profiles
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End point type |
Secondary
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End point timeframe |
0-12 months
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Attachments |
Consort Flowchart Dosing Schedules |
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
0-12 MONTHS
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
Whole Trial
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Reporting group description |
All participants received either Etanacept or Adalimumab | ||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Please see uploaded Adverse Event chart. |
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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16 Aug 2011 |
Amendment to remove the requirementfor additional Clinical Trial labelling for the IMPs and NIMPs. Also to request return of excess TNF inhibitors at month 12 to patients (re-labelled with the routine dosing instructions) to avoid destruction and wastage of expensive IMPs. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/28968858 |