Clinical Trial Results:
Inhibition of Co-Stimulation in Rheumatoid Arthritis
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Summary
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EudraCT number |
2014-004419-35 |
Trial protocol |
GB |
Global end of trial date |
02 May 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Nov 2023
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First version publication date |
25 Nov 2023
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Other versions |
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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 |
GN13RH410
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02652273 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
NHS Greater Glasgow and Clyde
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Sponsor organisation address |
Dykebar Hospital, Paisley, United Kingdom, PA2 7DE
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Public contact |
Dr Maureen Travers, NHS Greater Glasgow and Clyde, 0044 141 314 4012, Maureen.Travers@ggc.scot.nhs.uk
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Scientific contact |
Dr Maureen Travers, NHS Greater Glasgow and Clyde, 0044 141 314 4012, Maureen.Travers@ggc.scot.nhs.uk
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Sponsor organisation name |
University of Glasgow
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Sponsor organisation address |
University Avenue, Glasgow, United Kingdom, G12 8QQ
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Public contact |
Dr Debra Stuart, University of Glasgow, 0044 141 232 1798, debra.stuart@glasgow.ac.uk
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Scientific contact |
Dr Debra Stuart, University of Glasgow, 0044 141 232 1798, debra.stuart@glasgow.ac.uk
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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 Feb 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
02 May 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
02 May 2019
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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 primary endpoint of this study is the characterisation of the immune response to citrullinated peptides by T cells following costimulatory modulation in RA patients at 12 weeks.
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Protection of trial subjects |
1) Like all the other biologics and treatments used for RA, abatacept has the potential to increase the risk of infections. As participants will receive abatacept as part of their clinical practice, regardless of participation in the study, there is therefore no additional treatment risk associated with participation in the study above that associated with routine care. Participants will still be counselled about potential adverse effects and infections as per standard clinical practice. Similarly, study participants, or a relative, will be trained in subcutaneous injection techniques. Training will be provided by experienced practitioners in line with standard clinical practice for abatacept and the other subcutaneous biologic agents used in RA. Any adverse effects will be treated as per routine clinical care, including discontinuation or interruption of abatacept according to standard protocols and clinical judgement.
2) Failure to respond: Decisions regarding response are generally only made at 6 months. As this study is only for 6 months, non responders will not be disadvantaged and will still have the option to switch therapy upon completion of the study, in line with routine care. There is no placebo arm in this study.
3) Blood volume: Study participants were invited to consent to blood sampling greater in volume than routine care. Sample volumes and timing have been carefully selected to minimise the burden on participants while still allowing investigation of the important inflammatory processes. We do not believe the proposed volumes pose any risk to participants’ health.
4) Venesection: Study participants will be asked to have blood taken more regularly than routine care (7 instead of 3 times). Venesection can lead to some shortlived pain/discomfort and potentially bruising at the site of venesection. Blood samples will be taken by staff experienced and, where possible, study samples will be taken at the same time as bloods for routine care.
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Background therapy |
Methotrexate at dose of 10-25mg/week, either orally or SC Methotrexate. Should be taken for at least 3 months with a stable dose for 1 month prior to enrolment. | ||
Evidence for comparator |
N/A | ||
Actual start date of recruitment |
01 Jun 2015
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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: 25
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Worldwide total number of subjects |
25
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EEA total number of subjects |
0
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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) |
20
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From 65 to 84 years |
5
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects where identified via clinicians who recommend treatment with a biologic agent. Participants were recruited via: • Rheumatology out-patient clinic visits • Referrals from other Rheumatology out-patient clinics • If required, in response to advertising in the secondary care sector, via posters or leaflets. | ||||||||||||
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Pre-assignment
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Screening details |
Subjects where identified via clinicians who recommend treatment with a biologic agent. Subjects had active RA and met the relevant local or national guidelines for treatment with a biologic agent, consistent with the license and SmPC. Subjects were invited to a screening visit to assess eligibility. Only subjects HLA-DRB1*0401/0404 positive were i | ||||||||||||
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Period 1
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Period 1 title |
Baseline (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
Blinding implementation details |
N/A
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Arms
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Arm title
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All Participants - Abatacept | ||||||||||||
Arm description |
All study subjects should receive a 125 mg subcutaneous injection of abatacept, followed by weekly subcutaneous injections of abatacept (125mg). | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Abatacept
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects will receive the standard dosage of 125 mg/ml and will then receive this weekly for 24 weeks. The total contents (1 ml) of the pre-filled syringe will be administered. No dose adjustments are permitted. Patients will receive study medication for 24 weeks. Patients may be trained to self-administer SC abatacept using the single-dose prefilled glass syringe according to local practices for the administration of biological therapy. Patients self-administering at home will be provided with detailed information and advised to contact the investigator or site staff in case they have experienced an AE/SAE or have any concerns. An injection diary will be provided and completed by all patients. Patients unable to self-administer will be asked if a relative can serve this purpose and if so appropriate training will be offered. Suitable injection sites are the front of the thigh and abdomen, except for the 5 cm area around the navel. Injection sites will be rotated.
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Baseline characteristics reporting groups
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Reporting group title |
Baseline
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Reporting group description |
- | ||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
All Participants - Abatacept
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Reporting group description |
All study subjects should receive a 125 mg subcutaneous injection of abatacept, followed by weekly subcutaneous injections of abatacept (125mg). | ||
Subject analysis set title |
Primary analysis
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Numbers in Primary analysis
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End point title |
Antigen-specific T cell responses pre- and post-treatment with abatacept [1] | ||||||
End point description |
Ex-vivo tetramer staining using a multi-colour flow-cytometry panel to investigate T cells specific for either of the 12 different citrullinated peptide epitopes and the expression of different markers on these cells.
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End point type |
Primary
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End point timeframe |
From Day 1 (first dose) to 12 weeks
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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: Statistical analysis was performed between subjects defined as responders (+) and non-responders (-) based on whether they had a reduction of >1.2 in DAS28-ESR score at week 12 compared to baseline. (Rather than separate treatment arms) |
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Attachments |
ICOSRA - Primary endpoint |
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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 |
2015 to May 2019
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Adverse event reporting additional description |
Serious Adverse Events
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
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Reporting groups
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Reporting group title |
All Participants
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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: Don't have access to this data to report |
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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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11 Feb 2016 |
Clarifications / minor amendments to the protocol, change in wording to the Patient Information Sheet, and inclusion of injection diary into the Patient Alert Card. |
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30 Jan 2017 |
Minor clarifications / amendents to the protocol, Update protocol version control number.
Outdated addresses and email details, now amended to accurately reflect contact details.
Changes to wording in WOCBP - S1 exclusion criteria; S5.2.3 eligibility criteria; S4 withdrawal of subjects,
new text inserted to make instructions more detailed and S5.2.3 .
Insertion of blood tests or study tests in S3.2 Trial Flowchart and throught relevant scheduled visits
throughout the protocol (S6.1.1 -S6.1.2S6.1.3, S6.1.4, S6.1.5, S6.2, S6.4. Tests not mentioned in error in current
protocol that were aveilable on the flowchart or scheduled vists.
IMP risks new text included in this section to fully explain IMP risks
Good Clinical Practice new text to be included to confirm that the study will be conducted according to Declaration of Helsinki Procedures
Addition of NHS Lanarkshire as Patient Identification Centre |
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18 Dec 2017 |
Addition of a site. Protocol has been updated to reflect this change. |
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05 Jun 2018 |
Change of Laboratory exclusion criteria; Glomerular Filtration rate from <60ml/min to <30ml/min. |
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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 | |||
