Trial Outcomes & Findings for Namilumab vs Adalimumab in Participants With Moderate to Severe Early Rheumatoid Arthritis Inadequately Responding to Methotrexate (NCT NCT02393378)

Last Updated: 2019-02-05

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

Baseline and Week 24

Results posted on

2019-02-05

Participant Flow

Participants took part in the study at 5 investigative sites in Estonia and Russian Federation from 08 April 2015 to 03 November 2016.

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.

Participant milestones

Participant milestones
Measure	Adalimumab 40 mg 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.	Namilumab 150 mg 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.
Overall Study STARTED	3	4
Overall Study COMPLETED	3	4
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Namilumab vs Adalimumab in Participants With Moderate to Severe Early Rheumatoid Arthritis Inadequately Responding to Methotrexate

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Adalimumab 40 mg n=3 Participants 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.	Namilumab 150 mg n=4 Participants 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.	Total n=7 Participants Total of all reporting groups
Age, Continuous	63.0 years STANDARD_DEVIATION 7.21 • n=5 Participants	61.3 years STANDARD_DEVIATION 6.90 • n=7 Participants	62.0 years STANDARD_DEVIATION 6.48 • n=5 Participants
Age, Customized 45 to 64 years	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Age, Customized >= 65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized White	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment Estonia	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Russia	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Height	171.7 cm STANDARD_DEVIATION 8.96 • n=5 Participants	162.5 cm STANDARD_DEVIATION 3.00 • n=7 Participants	166.4 cm STANDARD_DEVIATION 7.44 • n=5 Participants
Weight	106.67 kg STANDARD_DEVIATION 16.197 • n=5 Participants	78.83 kg STANDARD_DEVIATION 16.550 • n=7 Participants	90.76 kg STANDARD_DEVIATION 21.116 • n=5 Participants
Body Mass Index (BMI)	36.77 kg/m^2 STANDARD_DEVIATION 8.806 • n=5 Participants	29.68 kg/m^2 STANDARD_DEVIATION 5.844 • n=7 Participants	32.71 kg/m^2 STANDARD_DEVIATION 7.569 • n=5 Participants
Body Mass Index (BMI) Categories < 30 kg/m^2	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Body Mass Index (BMI) Categories >= 30 kg/m^2	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set included participants who received at least one dose of study medication. Here number analyzed is the number of participants who were evaluated for specific sub-score.

Outcome measures

Outcome measures
Measure	Adalimumab 40 mg n=3 Participants 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.	Namilumab 150 mg n=4 Participants 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.
Change From Baseline in Synovitis, Erosion and Bone Marrow Edema (Osteitis) Score at Week 24 Erosion Score, Change at Week 24	0.50 score on a scale Standard Deviation 0.866	0.00 score on a scale Standard Deviation 0.500
Change From Baseline in Synovitis, Erosion and Bone Marrow Edema (Osteitis) Score at Week 24 Synovitis Score, Change at Week 24	0.17 score on a scale Standard Deviation 0.764	-1.50 score on a scale Standard Deviation 4.770
Change From Baseline in Synovitis, Erosion and Bone Marrow Edema (Osteitis) Score at Week 24 Osteitis Score, Change at Week 24	-0.33 score on a scale Standard Deviation 0.764	-2.00 score on a scale Standard Deviation 3.536

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set included participants who received at least one dose of study medication. Hence, number analyzed is the number of participants who were evaluated for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Adalimumab 40 mg n=3 Participants 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.	Namilumab 150 mg n=3 Participants 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.
Change From Baseline in Dynamic Contrast-enhanced - Magnetic Resonance Imaging (DCE-MRI) Parameters at Week 24	0.016 mL Standard Deviation 0.0253	-0.052 mL Standard Deviation 0.0662

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set included participants who received at least one dose of study medication.

Remission is defined as the number of participants who achieved Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) score \<2.6. The 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 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.

Outcome measures

Outcome measures
Measure	Adalimumab 40 mg n=3 Participants 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.	Namilumab 150 mg n=4 Participants 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.
Number of Participants Who Achieved Remission at Week 24	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set included participants who received at least one dose of study medication.

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.

Outcome measures

Outcome measures
Measure	Adalimumab 40 mg n=3 Participants 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.	Namilumab 150 mg n=4 Participants 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.
Number of Participants Who Achieved Low Disease Activity at Week 24	2 Participants	4 Participants

SECONDARY outcome

Timeframe: Week 24

Population: Full analysis set included participants who received at least one dose of study medication.

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.

Outcome measures

Outcome measures
Measure	Adalimumab 40 mg n=3 Participants 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.	Namilumab 150 mg n=4 Participants 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.
Number of Participants Who Achieved ACR 20, 50, and 70 at Week 24 ACR 50	2 Participants	3 Participants
Number of Participants Who Achieved ACR 20, 50, and 70 at Week 24 ACR 70	1 Participants	2 Participants
Number of Participants Who Achieved ACR 20, 50, and 70 at Week 24 ACR 20	2 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline Up to Week 42

Population: Full analysis set included participants who received at least one dose of study medication. Here number analyzed is the number of participants who were evaluated at specific time point.

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.

Outcome measures

Outcome measures
Measure	Adalimumab 40 mg n=3 Participants 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.	Namilumab 150 mg n=4 Participants 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.
Change From Baseline in DAS28-CRP Score Week 2	-0.55 score on a scale Standard Deviation 0.737	-0.78 score on a scale Standard Deviation 0.333
Change From Baseline in DAS28-CRP Score Week 6	-1.36 score on a scale Standard Deviation 1.086	-1.58 score on a scale Standard Deviation 0.494
Change From Baseline in DAS28-CRP Score Week 10	-1.74 score on a scale Standard Deviation 1.103	-1.83 score on a scale Standard Deviation 0.344
Change From Baseline in DAS28-CRP Score Week 12	-1.94 score on a scale Standard Deviation 1.036	-2.12 score on a scale Standard Deviation 0.613
Change From Baseline in DAS28-CRP Score Week 18	-2.05 score on a scale Standard Deviation 1.136	-2.72 score on a scale Standard Deviation 0.486
Change From Baseline in DAS28-CRP Score Week 24	-2.04 score on a scale Standard Deviation 1.596	-2.99 score on a scale Standard Deviation 0.216
Change From Baseline in DAS28-CRP Score Week 32	-1.89 score on a scale Standard Deviation 1.946	-2.38 score on a scale Standard Deviation 0.862
Change From Baseline in DAS28-CRP Score Week 42	-1.99 score on a scale Standard Deviation 1.938	-1.57 score on a scale Standard Deviation 1.387

Adverse Events

Adalimumab 40 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Namilumab 150 mg

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Adalimumab 40 mg n=3 participants at risk 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.	Namilumab 150 mg n=4 participants at risk 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.
Infections and infestations Cellulitis streptococcal	0.00% 0/3 • Baseline up to Week 42 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.	25.0% 1/4 • Baseline up to Week 42 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.

Other adverse events

Other adverse events
Measure	Adalimumab 40 mg n=3 participants at risk 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.	Namilumab 150 mg n=4 participants at risk 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.
Infections and infestations Streptococcal sepsis	0.00% 0/3 • Baseline up to Week 42 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.	25.0% 1/4 • Baseline up to Week 42 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.
Infections and infestations Urinary tract infection	33.3% 1/3 • Baseline up to Week 42 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.	25.0% 1/4 • Baseline up to Week 42 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.
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/3 • Baseline up to Week 42 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.	25.0% 1/4 • Baseline up to Week 42 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.
Blood and lymphatic system disorders Neutropenia	33.3% 1/3 • Baseline up to Week 42 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.	0.00% 0/4 • Baseline up to Week 42 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.
General disorders Pyrexia	0.00% 0/3 • Baseline up to Week 42 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.	25.0% 1/4 • Baseline up to Week 42 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.
Investigations Alanine aminotransferase increased	0.00% 0/3 • Baseline up to Week 42 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.	25.0% 1/4 • Baseline up to Week 42 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.
Investigations Aspartate aminotransferase increased	0.00% 0/3 • Baseline up to Week 42 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.	25.0% 1/4 • Baseline up to Week 42 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.
Investigations Forced expiratory volume decreased	0.00% 0/3 • Baseline up to Week 42 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.	25.0% 1/4 • Baseline up to Week 42 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.
Investigations Forced vital capacity decreased	33.3% 1/3 • Baseline up to Week 42 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.	0.00% 0/4 • Baseline up to Week 42 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.
Investigations Neutrophil count decreased	0.00% 0/3 • Baseline up to Week 42 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.	25.0% 1/4 • Baseline up to Week 42 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.
Nervous system disorders Syncope	0.00% 0/3 • Baseline up to Week 42 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.	25.0% 1/4 • Baseline up to Week 42 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.
Psychiatric disorders Panic attack	0.00% 0/3 • Baseline up to Week 42 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.	25.0% 1/4 • Baseline up to Week 42 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.
Vascular disorders Hypotension	0.00% 0/3 • Baseline up to Week 42 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.	25.0% 1/4 • Baseline up to Week 42 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.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER