Clinical Trial Results:
A 24-week Randomized, Open-Label, Parallel-Group, Active-Controlled, Exploratory, Proof-of-Mechanism Imaging Study Investigating the Efficacy of 150 mg of Namilumab Administered Subcutaneously vs Adalimumab in Patients With Moderate to Severe Early Rheumatoid
Arthritis Inadequately Responding to Methotrexate
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Summary
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EudraCT number |
2014-002945-23 |
Trial protocol |
GB CZ EE ES |
Global end of trial date |
03 Nov 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Nov 2017
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First version publication date |
26 Nov 2017
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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 |
MT203-2004
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02393378 | ||
WHO universal trial number (UTN) |
U1111-1160-1791 | ||
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Sponsors
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Sponsor organisation name |
Takeda
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Sponsor organisation address |
One Takeda Parkway Deerfield, Unites Sates, United States, IL 60015
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Public contact |
Medical Director, Clinical Science, Takeda, +1 877-825-3327, clinicaltrialregistry@tpna.com
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Scientific contact |
Medical Director, Clinical Science, Takeda, +1 877-825-3327, clinicaltrialregistry@tpna.com
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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 |
03 Nov 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Nov 2016
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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 |
To explore the effect on structural damage imaging markers measured as change from Baseline in synovitis, erosion, and bone marrow edema (osteitis), in metacarpophalangeal (MCP) joints and wrist at Week 24 on magnetic resonance imaging (MRI) using the RA-MRI scoring Outcome Measures in Rheumatoid Arthritis Clinical Trials (RAMRIS OMERACT).
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Protection of trial subjects |
All study participants were required to read and sign an Informed Consent Form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
08 Apr 2015
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
5 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Estonia: 3
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Country: Number of subjects enrolled |
Russian Federation: 4
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Worldwide total number of subjects |
7
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EEA total number of subjects |
3
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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) |
4
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants took part in the study at 5 investigative sites in Estonia and Russian Federation from 08 April 2015 to 03 November 2016. | |||||||||
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Pre-assignment
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Screening details |
Participants with a diagnosis of rheumatoid arthritis were enrolled in 2:1 ratio to receive either namilumab combined with methotrexate (MTX) or adalimumab combined with MTX. | |||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Adalimumab 40 mg | |||||||||
Arm description |
Adalimumab 40 mg SC injection at Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22 as an add-on to weekly existing stable MTX and folic acid as prescribed in clinical practice. | |||||||||
Arm type |
Experimental | |||||||||
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 |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants received Adalimumab 40 mg SC injection at Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.
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Arm title
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Namilumab 150 mg | |||||||||
Arm description |
Namilumab 300 mg SC injection at Week 0 followed by 150 mg SC injection at Weeks 2, 6, 10, 14, 18, and 22 as an add-on to weekly existing stable MTX and folic acid as prescribed in clinical practice. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Namilumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Participants received Namilumab 300 mg SC injection at Week 0 followed by 150 mg SC injection at Weeks 2, 6, 10, 14, 18, and 22.
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Baseline characteristics reporting groups
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Reporting group title |
Adalimumab 40 mg
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Reporting group description |
Adalimumab 40 mg SC injection at Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22 as an add-on to weekly existing stable MTX and folic acid as prescribed in clinical practice. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Namilumab 150 mg
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Reporting group description |
Namilumab 300 mg SC injection at Week 0 followed by 150 mg SC injection at Weeks 2, 6, 10, 14, 18, and 22 as an add-on to weekly existing stable MTX and folic acid as prescribed in clinical practice. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Adalimumab 40 mg
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Reporting group description |
Adalimumab 40 mg SC injection at Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22 as an add-on to weekly existing stable MTX and folic acid as prescribed in clinical practice. | ||
Reporting group title |
Namilumab 150 mg
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Reporting group description |
Namilumab 300 mg SC injection at Week 0 followed by 150 mg SC injection at Weeks 2, 6, 10, 14, 18, and 22 as an add-on to weekly existing stable MTX and folic acid as prescribed in clinical practice. | ||
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End point title |
Change from Baseline in Synovitis, Erosion and Bone Marrow Edema (Osteitis) Score at Week 24 [1] | |||||||||||||||||||||
End point description |
A Magnetic Resonance Imaging (MRI) of Metacarpophalangeal (MCP) and Wrist of the dominant hand was performed at the baseline and at week 24. Change from the Baseline was assessed according to the Outcome Measures in Rheumatoid Arthritis (RA) Clinical Trials RA-MRI scoring (OMERACT RAMRIS) Standard. RAMRIS score is the sum of its core components: Synovitis Score, Edema Score, and Erosion Score. Synovitis is scored from 0 (normal) to 9 (maximum distension of synovial cavity). Edema is scored 0 (normal) to 69 (maximum articular bone involvement). Erosion is scored from 0 (normal) to 230 (maximum erosion of articular bone). Total RAMRIS score=0 (normal), maximum RAMRIS score=308 (severe structural damage). For Synovial Score, Edema Score, Erosion Score, and RAMRIS score, increasing number = increasing severity. Full analysis set included participants who received at least one dose of study medication. Here 'n' is the number of participants who were evaluated for specific sub-score.
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End point type |
Primary
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End point timeframe |
Baseline and Week 24
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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 not assessed for this endpoint. |
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Change from Baseline in Dynamic Contrast-enhanced - Magnetic Resonance Imaging (DCE-MRI) Parameters at Week 24 | ||||||||||||
End point description |
DCE-MRI was used to measure synovial vascular perfusion. The change from baseline in DCE-MRI parameters of synovial vascular perfusion at Week 24 were measured. Full analysis set included participants who received at least one dose of study medication. Hence, number of participants analyzed (N) is the participants who were evaluated for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 24
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Participants who Achieved Remission at Week 24 | |||||||||
End point description |
Remission is defined as percentage of participants who achieved Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) score <2.6. DAS28-CRP is a composite measure of inflammation in rheumatoid arthritis (RA) and incorporates a tender and swollen joint count, CRP and patient global assessment of disease activity expressed in a gaussian distribution of variables ranging from 0 to 10. A DAS28-CRP score of <3.2 = low level of disease activity, while a score of >5.1 = high level of disease activity. Using DAS-CRP as a continuous scale allows investigators (and clinicians) to measure a clinically meaningful endpoint following institution of a therapeutic intervention. In RA, clinical remission would therefore be graded as a DAS28 score of ≤2.6 with disease flare accompanying scores of ≥5.1; well-controlled disease is best characterized as fitting in between these two scores. Full analysis set included participants who received at least one dose of study medication.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants who Achieved Low Disease Activity at Week 24 | |||||||||
End point description |
Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) low disease activity is defined as a score <3.2. The DAS28-CRP is a composite measure of inflammation in RA and incorporates a tender and swollen joint count, CRP and patient global assessment of disease activity expressed in a gaussian distribution of variables ranging from 0 to 10. A DAS28-CRP score of <3.2 suggests a low level of disease activity, while a score of >5.1 suggests a high level of disease activity. Using the DAS-CRP as a continuous scale allows investigators (and clinicians) to measure a clinically meaningful endpoint following institution of a therapeutic intervention. In RA, clinical remission would therefore be graded as a DAS28 score of ≤2.6 with disease flare accompanying scores of ≥5.1; well-controlled disease is best characterized as fitting in between these two scores. Full analysis set included participants who received at least one dose of study medication.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | ||||||||||
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End point title |
Percentage of Participants who Achieved ACR 20, 50, and 70 at Week 24 | ||||||||||||||||||
End point description |
The American College of Rheumatology (ACR) 20 is composite index of improvement in RA proposed by the ACR. ACR20 refers to a composite improvement of 20% in swollen joint count, tender joint count, and 3 or more of the following 5 measures: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, Patient Pain VAS, Patient's self-addressed disability (HAQ), Acute-phase reactant (ESR or CRP) The ACR 50 and ACR 70 are similar tools, used to indicate 50% and 70% improvement, respectively. Full analysis set included participants who received at least one dose of study medication.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change from Baseline in DAS28-CRP | ||||||||||||||||||||||||||||||||||||
End point description |
The DAS28-CRP is a composite measure of inflammation in RA and incorporates a tender and swollen joint count, CRP and patient global assessment of disease activity expressed in a gaussian distribution of variables ranging from 0 to 10. A DAS28-CRP score of <3.2 suggests a low level of disease activity, while a score of >5.1 suggests a high level of disease activity. Using the DAS-CRP as a continuous scale allows investigators (and clinicians) to measure a clinically meaningful endpoint following institution of a therapeutic intervention. In RA, clinical remission would therefore be graded as a DAS28 score of ≤3.2 with disease flare accompanying scores of ≥5.1; well-controlled disease is best characterized as fitting in between these two scores. Full analysis set included participants who received at least one dose of study medication. Here 'n' is the number of participants who were evaluated at specific time point.
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End point type |
Secondary
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End point timeframe |
Baseline Up to Week 42
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to Week 42
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Adverse event reporting additional description |
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
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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 |
19.0
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Reporting groups
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Reporting group title |
Namilumab 150 mg
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Reporting group description |
Namilumab 300 mg SC injection at Week 0 followed by 150 mg SC injection at Weeks 2, 6, 10, 14, 18, and 22 as an add-on to weekly existing stable MTX and folic acid as prescribed in clinical practice. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Adalimumab 40 mg
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Reporting group description |
Adalimumab 40 mg SC injection at Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22 as an add-on to weekly existing stable MTX and folic acid as prescribed in clinical practice. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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07 Apr 2015 |
• Clarified of inclusion and exclusion criteria.
• Increased of the screening period from 4 weeks to 8 weeks.
• Added flexibility around scheduling assessments at each visit. Allowing visits to be performed over two consecutive days.
• Revised contraceptive advice. |
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11 Feb 2016 |
• Updated to the inclusion criteria about onset of early rheumatoid arthritis (RA).
• Updated to exclusion criteria around lung function and management of associated adverse events.
• Updated to the pulmonary alvelolar proteinosis (PAP) language.
• Clarified and updated: Schedule of Study Procedures.
• Results of the new 26-week monkey study and calculation of the new safety margin added.
• Takeda made the strategic decision to stop the TELLUS study on 18 December 2015 but allow all the patients already enrolled to complete all the assessments as per protocol. The sample size and the number of sites are consequently reduced to match the recruitment status at the time of the decision. |
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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 | |||
