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MSB11022 in Moderate to Severe Rheumatoid Arthritis (Auriel-RA)

Primary Purpose

Moderate to Severe Rheumatoid Arthritis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
MSB11022
EU-Humira
Sponsored by
Fresenius Kabi SwissBioSim GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Moderate to Severe Rheumatoid Arthritis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of rheumatoid arthritis based on 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria
  • At least 6 tender (of 68 assessed) and 6 swollen (of 66 assessed) joints at screening and baseline
  • Must have received methotrexate for at least 12 weeks and been on a stable dose for at least 4 weeks prior to the first study dose
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • Evidence of untreated or inadequately treated latent or active Tuberculosis
  • Evidence of uncontrolled, clinically significant diseases
  • Any second disease-modifying antirheumatic drugs must be washed out prior to the first study dose
  • Other protocol defined exclusion criteria could apply

Sites / Locations

  • MHAT "Trimontium", OOD
  • MHAT-Plovdiv AD
  • UMHAT "Kaspela", EOOD
  • Medical Center "Teodora", EOOD
  • MHAT - Ruse, AD
  • MHAT - Shumen, AD
  • MHAT "Lyulin", EAD
  • Medical Center "Excelsior", OOD
  • UMHAT "Sv. Ivan Rilski", EAD
  • DCC 17 - Sofia EOOD
  • Military Medical Academy - MHAT - Sofia
  • MC "Synexus - Sofia", EOOD
  • Revmatologie Bruntal, s.r.o.
  • Ccbr-Synarc A/S
  • A-SHINE s.r.o.
  • CLINTRIAL s.r.o.
  • Revma Praha, s.r.o.
  • Revmatologicky Ustav
  • Revmatologicka ambulance
  • Nuselska poliklinika
  • MEDICAL PLUS s.r.o.
  • PV - Medical, s.r.o.
  • Studienambulanz Dr. Wassenberg
  • HRF Hamburger Rheuma Forschungszentrum
  • Dr. Kenessey Albert Korhaz-Rendelointezet
  • Revita Reumatologiai Rendelo
  • Obudai Egeszsegugyi Centrum Kft.
  • DRC Szekesfehervar
  • Mentahaz Maganorvosi Kozpont
  • Vital Medical Center
  • Synexus Magyarorszag Egeszsegugyi Szolgaltato Kft.- Zalaegerszeg AS
  • KLIMED Marek Klimkiewicz
  • ClinicMed Badurski i wspolnicy Spolka Jawna
  • Szpital Uniwersytecki nr 2 im.dr J. Biziela
  • Centrum Medyczne Angelius Provita
  • Malopolskie Centrum Medyczne s.c.
  • Centrum Terapii Wspolczesnej J.M. Jasnorzewska sp. komandytowo-akcyjna
  • KLIMED Marek Klimkiewicz
  • RCMed
  • ETYKA Osrodek Badan Klinicznych
  • Niepubliczny Zaklad Opieki Zdrowotnej "Nasz Lekarz" Praktyka Grupowa Lekarzy Rodzinnych z
  • Medycyna Kliniczna
  • Rheuma Medicus Zaklad Opieki Zdrowotnej
  • Niepubliczny Zakład Opieki Zdrowotnej "Biogenes" Sp. z o.o.
  • Glasgow Royal Infirmary
  • Whipps Cross University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

MSB11022

EU-Humira

Arm Description

Outcomes

Primary Outcome Measures

Percentage of Participants With Treatment-emergent Adverse Events of Special Interest (AESI)
Adverse event (AE) was defined as any untoward medical occurrence in participants, which does not necessarily have causal relationship with treatment. Term Treatment-emergent Adverse Events (TEAE) is defined as AEs starting/worsening after first intake of the study drug. Hypersensitivity was the pre-defined TEAE of special Interest for this study. The percentage of participants with treatment emergent AESIs (hypersensitivity) were reported.

Secondary Outcome Measures

Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 12
The ACR 20 Response is defined as greater than or equal to (>=) 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=20 percent improvement in 3 of following 5 assessments: participant's assessment of pain using Visual Analog Scale (VAS ; 0-10 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), participant's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas). The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and acute-phase marker (CRP).
Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) Status to Adalimumab
Percentage of participants with positive anti-Drug antibodies (ADAs) status to Adalimumab were reported.
Anti-Drug Antibodies (ADAs) Titer Levels for Adalimumab
Titer was defined as the degree to which the antibody-serum sample could be diluted and still contained detectable amounts of antibody. Anti-Drug Antibodies (ADAs) titers for adalimumab was reported. Data was collected using validated bioanalytical method.
Percentage of Participants With Confirmed Neutralizing Antibodies (NAb) Status to Adalimumab
Percentage of participants with confirmed neutralizing antibodies status to Adalimumab were reported.
Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 2, 4, 8, 24 and 52
The ACR 20 Response is defined as greater than or equal to (>=) 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS ; 0-10 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas). The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and acute-phase marker (CRP).
Percentage of Participants Who Achieved American College of Rheumatology 50 (ACR50) Response at Week 2, 4, 8, 12, 24 and 52
The ACR 50 Response is defined as greater than or equal to (>=) 50 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=50 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS ; 0-10 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas). The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and acute-phase marker (CRP).
Percentage of Participants Who Achieved American College of Rheumatology 70 (ACR70) Response at Week 2, 4, 8, 12, 24 and 52
The ACR 70 Response is defined as greater than or equal to (>=) 70 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=70 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS ; 0-10 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas). The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and acute-phase marker (CRP).
Change From Baseline in Disease Activity Score Based on a 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 2, 4, 8, 12, 24 and 52
DAS calculated on 28 joints is composite score derived from 4 measures: number of swollen joints (out of 28), number of tender joints (out of 28), Erythrocyte sedimentation rate (ESR), Patient's Global Assessment of Disease Activity on visual analog scale (VAS). Overall disease activity score DAS28 was derived using following formulas from DAS28:DAS28=0.56*√(TJC28)+0.28*√(SJC28) + 0.014*GH+0.70*ln(ESR). Where: TJC28 = 28 joint count for tenderness, SJC28 = 28 joint count for swelling, ln(ESR) = natural log of ESR, GH = general health component of DAS (ie, Patient's Global Assessment of Disease Activity, assessed using scale of 1-100 where 100 is maximal activity); For analyses, GH divided by 10 & converted to 0.5 scale, i.e, 0, 0.5, 1, 1.5. DAS28-ESR of >5.1 implies active disease, <3.2 low disease activity, & <2.6 remission. Change of 1.2(twice measurement error)=significant change of disease activity state. Overall score ranges from 0-10 where higher score means more severe disease.
Percentage of Participants With Disease Activity Score Based on 28-joints Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Low Disease Activity and Remission at Week 2, 4, 8, 12, 24, and 52
Disease Activity Score calculated on 28 joints is composite score derived from 4 measures: number of swollen joints (out of 28), -number of tender joints (out of 28), -Erythrocyte sedimentation rate (ESR), -Patient's Global Assessment of Disease Activity on visual analog scale (VAS). Overall disease activity score DAS28 was derived using following formulas from DAS28: DAS28=0.56*√(TJC28)+0.28*√(SJC28) + 0.014*GH+0.70*ln(ESR). Where: -TJC28 = 28 joint count for tenderness, -SJC28 = 28 joint count for swelling, -ln(ESR) = natural logarithm of ESR, -GH = general health component of DAS (ie, Patient's Global Assessment of Disease Activity, assessed using scale of 1 to 100 where 100 is maximal activity); For analyses, GH was divided by 10 and converted to a 0.5 scale, i.e., 0, 0.5, 1, 1.5. DAS28-ESR of >5.1 implies active disease, <3.2 low disease activity, and <2.6 remission.
Change From Baseline in Simplified Disease Activity Index (SDAI) Total Score at Week 2, 4, 8, 12, 24, and 52
SDAI is numerical sum of 5 outcome parameters: tender & swollen joint count (based on 28-joint assessment), Patient's & Physician's Global Assessment of Disease Activity (VAS) & level of C-reactive protein (CRP)(milligram per deciliter (mg/dL), normal<1 mg/dL). SDAI was calculated based on following formula: SDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28)+GH+PGA+CRP Where: -GH =general health component of DAS (i.e. Patient's Global Assessment of Disease Activity, assessed using scale of 1 to 100 where 100 is maximal activity; For analyses, GH was divided by 10 & converted to 0.5 scale (0, 0.5, 1, 1.5).-PGA = Physician's Global Assessment of Disease Activity assessed using scale of 1 to 100 where 100 is maximal activity. For analyses, PGA will be divided by 10 & converted to 0.5 scale (0, 0.5, 1, 1.5). where [0-0.25] = 0, [0.25-0.75] = 0.5, [0.76-1.25] = 1, etc. The total score range is 0-86 & lower score indicates less disease activity.
Change From Baseline in Clinical Disease Activity Index (CDAI) Total Score at Week 2, 4, 8, 12, 24 and 52
Clinical Disease Activity Index (CDAI) is a composite index (without acute-phase reactant) for assessing disease activity. The CDAI was calculated based on following formula: CDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA. Where, -GH = general health component of the DAS (i.e., Patient's Global Assessment of Disease Activity, assessed using a scale of 1 to 100 where 100 is maximal activity; for analyses, GH was divided by 10 and converted to a 0.5 scale, i.e., 0, 0.5, 1, 1.5 etc. where [0-0.25] = 0, [0.25-0.75] = 0.5, [0.76-1.25] = 1, etc.). -PGA = Physician's Global Assessment of Disease Activity assessed using a scale of 1 to 100 where 100 is maximal activity. For analyses, PGA was divided by 10 and converted to a 0.5 scale, ie, 0, 0.5, 1, 1.5 etc. where [0-0.25] = 0, [0.25-0.75] = 0.5, [0.76-1.25] = 1, etc. The CDAI ranges from 0 to 76. Lower score indicates less disease activity.
Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission at Week 2, 4, 8, 12, 24 and 52
According to Boolean-based definition of remission of ACR/EULAR, a participant must satisfy all of the following: tender joint count <= 1, swollen joint count <= 1, CRP <= 1 mg/dL, and Patient's Global Assessment of Disease Activity <= 1 (0 to 10 VAS). PGA was assessed on a 10 mm VAS ranging from 0 (very well) to 10 (very poor), where higher scores indicate worse health condition.
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
Adverse event(AE) was defined as any untoward medical occurrence in participants which does not necessarily have causal relationship with treatment. A serious adverse event(SAE) was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. All abnormal physical examinations occurring during the study have been reported as Adverse events. TEAEs included both Serious TEAEs and non-serious TEAEs.
Percentage of Participants With Clinically Meaningful Differences in Vital Signs
Vital signs including body temperature, respiratory rate, and heart rate (after 5-minute rest) were measured. Percentage of participants with clinically meaningful abnormalities in vital signs were reported. Clinical meaningful was determined by the investigator.
Percentage of Participants With Clinically Meaningful Differences in Laboratory Values
Laboratory parameters including hematology, urinalysis, and biochemistry analysis were analyzed.
Percentage of Participants With Clinically Significant Abnormal Values for 12-lead Electrocardiogram (ECG) at Week 12, 24, and 52
Percentage of participants with clinically significant abnormal values for 12-lead electrocardiogram (ECG) at week 12, 24, and 52 were reported.
Percentage of Participants With Anti-Nuclear Antibody (ANA) and Anti Double-stranded Deoxyribonucleic Acid (Anti-dsDNA) at Baseline, Week 24 and 52
For ANA, positivity is defined as any participant with ANA titer greater than (>) 1:160 and negativity is defined as ANA titer less than (<) 1:160. For anti-ds DNA, positivity is defined as any participant with adsDNA > 15 units per milliliter (U/mL), intermediate category is defined as value between 10 U/mL to 15 U/mL and negativity is defined as adsDNA < 10 U/mL. Percentage of participants with anti-nuclear antibody (ANA) and anti double-stranded deoxyribonucleic acid (Anti-dsDNA) at baseline, week 24 and 52 were reported.
Health Assessment Questionnaire Disability Index (HAQ-DI) Total Score at Baseline, Weeks 12, 24 and 52
The HAQ-DI is a participant-reported questionnaire that is commonly used in RA to measure disease associated disability (assessment of physical function). It consists of several questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. HAQ-DI scores range from 0 to 3. The disability section of the questionnaire scores the participant's self-perception on the degree of difficulty (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do).
Short-Form Health Survey- 36 Items (SF-36) at Baseline, Week 12, 24 and 52
The Short Form Health Survey (SF-36) is a validated 36-item, patient-reported indication of overall health status not specific to any age, disease or Treatment group. The SF-36 questionnaire contains 36 questions pertaining to eight subscales of health status. These eight subscales were summarized as relating to either physical health or mental health. Physical component summary (PCS) is based primarily on physical functioning, role-physical, bodily pain, and general health scales and mental component summary (MCS) encompasses vitality, social functioning, role-emotional, and mental health scales. Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0-100 (100=highest level of mental functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100=highest level of physical functioning).
Euro-Quality of Life - 5 Dimension-5 Levels (EQ-5D-5L) Utility Index Score at Baseline, Week 12, 24 and 52
EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The EQ-5D-5L descriptive system provides a profile of the participant's health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The participant was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. Responses to the 5 dimension scores were combined and converted into a single preference-weighted health utility index score 0 (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of the individual based on the UK scoring algorithm.
Euro-Quality of Life - 5 Dimension-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Score at Baseline, Week 12, 24 and 52
EQ-5D-5L: Standardized, participant-rated questionnaire to assess health-related quality of life. EQ-5D-5L includes 2 components: EQ-5D-5L health state profile (descriptive system) and EQ-5D-5L Visual Analog Scale. EQ-5D-5L descriptive system provides a profile of participant's health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. Responses to 5 dimension scores were combined and converted into single preference-weighted health utility index score 0 (worst health state) to 1 (better health state). EQ-VAS: Self-rated health status using a vertical VAS. EQ-VAS records participant's perceptions of their own current overall health in range from 0 (worst imaginable health) to 100 (best imaginable health).
Mean Change From Baseline (Week 4) in Injection Site Pain as Assessed by Visual Analogue Scale (VAS) at Week 6 and 8
The participant's reported perception of pain was measured on a VAS where the slash drawn by the participant represents pain of increasing intensity. VAS score ranges from 0-10 millimeter [mm], where; 0 mm=no pain and 10 mm=worst possible pain. The first 2 injections was administered by qualified personnel. The next three doses of IMP (3-5) will be self-administered by the participant and injection site pain was assessed. Pain was recorded immediately after, 15 minutes after, and 1 hour after the injections received by the participants.

Full Information

First Posted
January 29, 2017
Last Updated
December 13, 2019
Sponsor
Fresenius Kabi SwissBioSim GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT03052322
Brief Title
MSB11022 in Moderate to Severe Rheumatoid Arthritis
Acronym
Auriel-RA
Official Title
A Multicenter, Randomized, Double-blind, Phase III Trial to Evaluate the Safety, Immunogenicity, and Efficacy of MSB11022 Compared With Humira® in Patients With Moderately to Severely Active Rheumatoid Arthritis
Study Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
January 31, 2017 (Actual)
Primary Completion Date
May 28, 2018 (Actual)
Study Completion Date
August 27, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fresenius Kabi SwissBioSim GmbH

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to compare the efficacy, safety and immunogenicity of MSB11022 and Humira® in adult participants with rheumatoid arthritis (RA).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Moderate to Severe Rheumatoid Arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
288 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MSB11022
Arm Type
Experimental
Arm Title
EU-Humira
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
MSB11022
Other Intervention Name(s)
Adalimumab
Intervention Description
Participants received MSB11022 (modified buffer and stabilizer) subcutaneously at dose of 40 milligram (mg) every other week from Day 1 up to Week 48.
Intervention Type
Drug
Intervention Name(s)
EU-Humira
Intervention Description
Participants received EU-Humira subcutaneously at dose of 40 mg every other week from Day 1 up to Week 48.
Primary Outcome Measure Information:
Title
Percentage of Participants With Treatment-emergent Adverse Events of Special Interest (AESI)
Description
Adverse event (AE) was defined as any untoward medical occurrence in participants, which does not necessarily have causal relationship with treatment. Term Treatment-emergent Adverse Events (TEAE) is defined as AEs starting/worsening after first intake of the study drug. Hypersensitivity was the pre-defined TEAE of special Interest for this study. The percentage of participants with treatment emergent AESIs (hypersensitivity) were reported.
Time Frame
Up to Week 52
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 12
Description
The ACR 20 Response is defined as greater than or equal to (>=) 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=20 percent improvement in 3 of following 5 assessments: participant's assessment of pain using Visual Analog Scale (VAS ; 0-10 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), participant's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas). The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and acute-phase marker (CRP).
Time Frame
Week 12
Title
Percentage of Participants With Positive Anti-Drug Antibodies (ADAs) Status to Adalimumab
Description
Percentage of participants with positive anti-Drug antibodies (ADAs) status to Adalimumab were reported.
Time Frame
Baseline, Week 2, 4, 12, 24, 36 and 52
Title
Anti-Drug Antibodies (ADAs) Titer Levels for Adalimumab
Description
Titer was defined as the degree to which the antibody-serum sample could be diluted and still contained detectable amounts of antibody. Anti-Drug Antibodies (ADAs) titers for adalimumab was reported. Data was collected using validated bioanalytical method.
Time Frame
Baseline, Week 2, 4, 12, 24, 36 and 52
Title
Percentage of Participants With Confirmed Neutralizing Antibodies (NAb) Status to Adalimumab
Description
Percentage of participants with confirmed neutralizing antibodies status to Adalimumab were reported.
Time Frame
Baseline, Week 2, 4, 12, 24, 36 and 52
Title
Percentage of Participants Who Achieved American College of Rheumatology 20 (ACR20) Response at Week 2, 4, 8, 24 and 52
Description
The ACR 20 Response is defined as greater than or equal to (>=) 20 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=20 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS ; 0-10 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas). The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and acute-phase marker (CRP).
Time Frame
Week 2, 4, 8, 24 and 52
Title
Percentage of Participants Who Achieved American College of Rheumatology 50 (ACR50) Response at Week 2, 4, 8, 12, 24 and 52
Description
The ACR 50 Response is defined as greater than or equal to (>=) 50 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=50 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS ; 0-10 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas). The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and acute-phase marker (CRP).
Time Frame
Week 2, 4, 8, 12, 24 and 52
Title
Percentage of Participants Who Achieved American College of Rheumatology 70 (ACR70) Response at Week 2, 4, 8, 12, 24 and 52
Description
The ACR 70 Response is defined as greater than or equal to (>=) 70 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and >=70 percent improvement in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS ; 0-10 millimeter [mm], 0 mm=no pain and 10 mm=worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 mm to 100 mm, [0 mm=no pain to 100 mm=worst possible pain]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas). The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and acute-phase marker (CRP).
Time Frame
Week 2, 4, 8, 12, 24 and 52
Title
Change From Baseline in Disease Activity Score Based on a 28 Joint Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 2, 4, 8, 12, 24 and 52
Description
DAS calculated on 28 joints is composite score derived from 4 measures: number of swollen joints (out of 28), number of tender joints (out of 28), Erythrocyte sedimentation rate (ESR), Patient's Global Assessment of Disease Activity on visual analog scale (VAS). Overall disease activity score DAS28 was derived using following formulas from DAS28:DAS28=0.56*√(TJC28)+0.28*√(SJC28) + 0.014*GH+0.70*ln(ESR). Where: TJC28 = 28 joint count for tenderness, SJC28 = 28 joint count for swelling, ln(ESR) = natural log of ESR, GH = general health component of DAS (ie, Patient's Global Assessment of Disease Activity, assessed using scale of 1-100 where 100 is maximal activity); For analyses, GH divided by 10 & converted to 0.5 scale, i.e, 0, 0.5, 1, 1.5. DAS28-ESR of >5.1 implies active disease, <3.2 low disease activity, & <2.6 remission. Change of 1.2(twice measurement error)=significant change of disease activity state. Overall score ranges from 0-10 where higher score means more severe disease.
Time Frame
Baseline, Week 2, 4, 8, 12, 24 and 52
Title
Percentage of Participants With Disease Activity Score Based on 28-joints Count- Erythrocyte Sedimentation Rate (DAS28-ESR) Low Disease Activity and Remission at Week 2, 4, 8, 12, 24, and 52
Description
Disease Activity Score calculated on 28 joints is composite score derived from 4 measures: number of swollen joints (out of 28), -number of tender joints (out of 28), -Erythrocyte sedimentation rate (ESR), -Patient's Global Assessment of Disease Activity on visual analog scale (VAS). Overall disease activity score DAS28 was derived using following formulas from DAS28: DAS28=0.56*√(TJC28)+0.28*√(SJC28) + 0.014*GH+0.70*ln(ESR). Where: -TJC28 = 28 joint count for tenderness, -SJC28 = 28 joint count for swelling, -ln(ESR) = natural logarithm of ESR, -GH = general health component of DAS (ie, Patient's Global Assessment of Disease Activity, assessed using scale of 1 to 100 where 100 is maximal activity); For analyses, GH was divided by 10 and converted to a 0.5 scale, i.e., 0, 0.5, 1, 1.5. DAS28-ESR of >5.1 implies active disease, <3.2 low disease activity, and <2.6 remission.
Time Frame
Week 2, 4, 8, 12, 24, and 52
Title
Change From Baseline in Simplified Disease Activity Index (SDAI) Total Score at Week 2, 4, 8, 12, 24, and 52
Description
SDAI is numerical sum of 5 outcome parameters: tender & swollen joint count (based on 28-joint assessment), Patient's & Physician's Global Assessment of Disease Activity (VAS) & level of C-reactive protein (CRP)(milligram per deciliter (mg/dL), normal<1 mg/dL). SDAI was calculated based on following formula: SDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28)+GH+PGA+CRP Where: -GH =general health component of DAS (i.e. Patient's Global Assessment of Disease Activity, assessed using scale of 1 to 100 where 100 is maximal activity; For analyses, GH was divided by 10 & converted to 0.5 scale (0, 0.5, 1, 1.5).-PGA = Physician's Global Assessment of Disease Activity assessed using scale of 1 to 100 where 100 is maximal activity. For analyses, PGA will be divided by 10 & converted to 0.5 scale (0, 0.5, 1, 1.5). where [0-0.25] = 0, [0.25-0.75] = 0.5, [0.76-1.25] = 1, etc. The total score range is 0-86 & lower score indicates less disease activity.
Time Frame
Baseline, Week 2, 4, 8, 12, 24, and 52
Title
Change From Baseline in Clinical Disease Activity Index (CDAI) Total Score at Week 2, 4, 8, 12, 24 and 52
Description
Clinical Disease Activity Index (CDAI) is a composite index (without acute-phase reactant) for assessing disease activity. The CDAI was calculated based on following formula: CDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA. Where, -GH = general health component of the DAS (i.e., Patient's Global Assessment of Disease Activity, assessed using a scale of 1 to 100 where 100 is maximal activity; for analyses, GH was divided by 10 and converted to a 0.5 scale, i.e., 0, 0.5, 1, 1.5 etc. where [0-0.25] = 0, [0.25-0.75] = 0.5, [0.76-1.25] = 1, etc.). -PGA = Physician's Global Assessment of Disease Activity assessed using a scale of 1 to 100 where 100 is maximal activity. For analyses, PGA was divided by 10 and converted to a 0.5 scale, ie, 0, 0.5, 1, 1.5 etc. where [0-0.25] = 0, [0.25-0.75] = 0.5, [0.76-1.25] = 1, etc. The CDAI ranges from 0 to 76. Lower score indicates less disease activity.
Time Frame
Baseline, Week 2, 4, 8, 12, 24 and 52
Title
Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean Remission at Week 2, 4, 8, 12, 24 and 52
Description
According to Boolean-based definition of remission of ACR/EULAR, a participant must satisfy all of the following: tender joint count <= 1, swollen joint count <= 1, CRP <= 1 mg/dL, and Patient's Global Assessment of Disease Activity <= 1 (0 to 10 VAS). PGA was assessed on a 10 mm VAS ranging from 0 (very well) to 10 (very poor), where higher scores indicate worse health condition.
Time Frame
Week 2, 4, 8, 12, 24 and 52
Title
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
Description
Adverse event(AE) was defined as any untoward medical occurrence in participants which does not necessarily have causal relationship with treatment. A serious adverse event(SAE) was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. All abnormal physical examinations occurring during the study have been reported as Adverse events. TEAEs included both Serious TEAEs and non-serious TEAEs.
Time Frame
Baseline up to Week 69
Title
Percentage of Participants With Clinically Meaningful Differences in Vital Signs
Description
Vital signs including body temperature, respiratory rate, and heart rate (after 5-minute rest) were measured. Percentage of participants with clinically meaningful abnormalities in vital signs were reported. Clinical meaningful was determined by the investigator.
Time Frame
Up to Week 52
Title
Percentage of Participants With Clinically Meaningful Differences in Laboratory Values
Description
Laboratory parameters including hematology, urinalysis, and biochemistry analysis were analyzed.
Time Frame
Up to Week 52
Title
Percentage of Participants With Clinically Significant Abnormal Values for 12-lead Electrocardiogram (ECG) at Week 12, 24, and 52
Description
Percentage of participants with clinically significant abnormal values for 12-lead electrocardiogram (ECG) at week 12, 24, and 52 were reported.
Time Frame
Week 12, 24, and 52
Title
Percentage of Participants With Anti-Nuclear Antibody (ANA) and Anti Double-stranded Deoxyribonucleic Acid (Anti-dsDNA) at Baseline, Week 24 and 52
Description
For ANA, positivity is defined as any participant with ANA titer greater than (>) 1:160 and negativity is defined as ANA titer less than (<) 1:160. For anti-ds DNA, positivity is defined as any participant with adsDNA > 15 units per milliliter (U/mL), intermediate category is defined as value between 10 U/mL to 15 U/mL and negativity is defined as adsDNA < 10 U/mL. Percentage of participants with anti-nuclear antibody (ANA) and anti double-stranded deoxyribonucleic acid (Anti-dsDNA) at baseline, week 24 and 52 were reported.
Time Frame
Baseline, Week 24 and 52
Title
Health Assessment Questionnaire Disability Index (HAQ-DI) Total Score at Baseline, Weeks 12, 24 and 52
Description
The HAQ-DI is a participant-reported questionnaire that is commonly used in RA to measure disease associated disability (assessment of physical function). It consists of several questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities. HAQ-DI scores range from 0 to 3. The disability section of the questionnaire scores the participant's self-perception on the degree of difficulty (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do).
Time Frame
Baseline, Weeks 12, 24 and 52
Title
Short-Form Health Survey- 36 Items (SF-36) at Baseline, Week 12, 24 and 52
Description
The Short Form Health Survey (SF-36) is a validated 36-item, patient-reported indication of overall health status not specific to any age, disease or Treatment group. The SF-36 questionnaire contains 36 questions pertaining to eight subscales of health status. These eight subscales were summarized as relating to either physical health or mental health. Physical component summary (PCS) is based primarily on physical functioning, role-physical, bodily pain, and general health scales and mental component summary (MCS) encompasses vitality, social functioning, role-emotional, and mental health scales. Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0-100 (100=highest level of mental functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100=highest level of physical functioning).
Time Frame
Baseline, Week 12, 24 and 52
Title
Euro-Quality of Life - 5 Dimension-5 Levels (EQ-5D-5L) Utility Index Score at Baseline, Week 12, 24 and 52
Description
EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The EQ-5D-5L descriptive system provides a profile of the participant's health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The participant was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. Responses to the 5 dimension scores were combined and converted into a single preference-weighted health utility index score 0 (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of the individual based on the UK scoring algorithm.
Time Frame
Baseline, Week 12, 24 and 52
Title
Euro-Quality of Life - 5 Dimension-5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS) Score at Baseline, Week 12, 24 and 52
Description
EQ-5D-5L: Standardized, participant-rated questionnaire to assess health-related quality of life. EQ-5D-5L includes 2 components: EQ-5D-5L health state profile (descriptive system) and EQ-5D-5L Visual Analog Scale. EQ-5D-5L descriptive system provides a profile of participant's health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. Responses to 5 dimension scores were combined and converted into single preference-weighted health utility index score 0 (worst health state) to 1 (better health state). EQ-VAS: Self-rated health status using a vertical VAS. EQ-VAS records participant's perceptions of their own current overall health in range from 0 (worst imaginable health) to 100 (best imaginable health).
Time Frame
Baseline, Week 12, 24 and 52
Title
Mean Change From Baseline (Week 4) in Injection Site Pain as Assessed by Visual Analogue Scale (VAS) at Week 6 and 8
Description
The participant's reported perception of pain was measured on a VAS where the slash drawn by the participant represents pain of increasing intensity. VAS score ranges from 0-10 millimeter [mm], where; 0 mm=no pain and 10 mm=worst possible pain. The first 2 injections was administered by qualified personnel. The next three doses of IMP (3-5) will be self-administered by the participant and injection site pain was assessed. Pain was recorded immediately after, 15 minutes after, and 1 hour after the injections received by the participants.
Time Frame
Immediately, 15 minutes and 1 hour post-injection on Baseline (Week 4), Week 6 and 8

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of rheumatoid arthritis based on 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria At least 6 tender (of 68 assessed) and 6 swollen (of 66 assessed) joints at screening and baseline Must have received methotrexate for at least 12 weeks and been on a stable dose for at least 4 weeks prior to the first study dose Other protocol defined inclusion criteria could apply Exclusion Criteria: Evidence of untreated or inadequately treated latent or active Tuberculosis Evidence of uncontrolled, clinically significant diseases Any second disease-modifying antirheumatic drugs must be washed out prior to the first study dose Other protocol defined exclusion criteria could apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Fresenius Kabi SwissBioSim GmbH
Official's Role
Study Director
Facility Information:
Facility Name
MHAT "Trimontium", OOD
City
Plovdiv
ZIP/Postal Code
4000
Country
Bulgaria
Facility Name
MHAT-Plovdiv AD
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
Facility Name
UMHAT "Kaspela", EOOD
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
Facility Name
Medical Center "Teodora", EOOD
City
Ruse
ZIP/Postal Code
7000
Country
Bulgaria
Facility Name
MHAT - Ruse, AD
City
Ruse
ZIP/Postal Code
7002
Country
Bulgaria
Facility Name
MHAT - Shumen, AD
City
Shumen
ZIP/Postal Code
9700
Country
Bulgaria
Facility Name
MHAT "Lyulin", EAD
City
Sofia
ZIP/Postal Code
1336
Country
Bulgaria
Facility Name
Medical Center "Excelsior", OOD
City
Sofia
ZIP/Postal Code
1407
Country
Bulgaria
Facility Name
UMHAT "Sv. Ivan Rilski", EAD
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Facility Name
DCC 17 - Sofia EOOD
City
Sofia
ZIP/Postal Code
1504
Country
Bulgaria
Facility Name
Military Medical Academy - MHAT - Sofia
City
Sofia
ZIP/Postal Code
1606
Country
Bulgaria
Facility Name
MC "Synexus - Sofia", EOOD
City
Sofia
ZIP/Postal Code
1784
Country
Bulgaria
Facility Name
Revmatologie Bruntal, s.r.o.
City
Bruntal
ZIP/Postal Code
792 01
Country
Czechia
Facility Name
Ccbr-Synarc A/S
City
Ostrava
ZIP/Postal Code
702 00
Country
Czechia
Facility Name
A-SHINE s.r.o.
City
Plzen
ZIP/Postal Code
31200
Country
Czechia
Facility Name
CLINTRIAL s.r.o.
City
Praha 10
ZIP/Postal Code
100 00
Country
Czechia
Facility Name
Revma Praha, s.r.o.
City
Praha 13
ZIP/Postal Code
158 00
Country
Czechia
Facility Name
Revmatologicky Ustav
City
Praha 2
ZIP/Postal Code
128 50
Country
Czechia
Facility Name
Revmatologicka ambulance
City
Praha 4 Nusle
ZIP/Postal Code
140 00
Country
Czechia
Facility Name
Nuselska poliklinika
City
Praha 4
ZIP/Postal Code
140 00
Country
Czechia
Facility Name
MEDICAL PLUS s.r.o.
City
Uherske Hradiste
ZIP/Postal Code
686 01
Country
Czechia
Facility Name
PV - Medical, s.r.o.
City
Zlin
ZIP/Postal Code
760 01
Country
Czechia
Facility Name
Studienambulanz Dr. Wassenberg
City
Ratingen
State/Province
Nordrhein Westfalen
ZIP/Postal Code
40882
Country
Germany
Facility Name
HRF Hamburger Rheuma Forschungszentrum
City
Hamburg
ZIP/Postal Code
20095
Country
Germany
Facility Name
Dr. Kenessey Albert Korhaz-Rendelointezet
City
Balassagyarmat
ZIP/Postal Code
2660
Country
Hungary
Facility Name
Revita Reumatologiai Rendelo
City
Budapest
ZIP/Postal Code
1023
Country
Hungary
Facility Name
Obudai Egeszsegugyi Centrum Kft.
City
Budapest
ZIP/Postal Code
1036
Country
Hungary
Facility Name
DRC Szekesfehervar
City
Szekesfehervar
ZIP/Postal Code
8000
Country
Hungary
Facility Name
Mentahaz Maganorvosi Kozpont
City
Szekesfehervar
ZIP/Postal Code
8000
Country
Hungary
Facility Name
Vital Medical Center
City
Veszprem
ZIP/Postal Code
8200
Country
Hungary
Facility Name
Synexus Magyarorszag Egeszsegugyi Szolgaltato Kft.- Zalaegerszeg AS
City
Zalaegerszeg
ZIP/Postal Code
8900
Country
Hungary
Facility Name
KLIMED Marek Klimkiewicz
City
Bialystok
ZIP/Postal Code
15-765
Country
Poland
Facility Name
ClinicMed Badurski i wspolnicy Spolka Jawna
City
Bialystok
ZIP/Postal Code
15-879
Country
Poland
Facility Name
Szpital Uniwersytecki nr 2 im.dr J. Biziela
City
Bydgoszcz
ZIP/Postal Code
85-168
Country
Poland
Facility Name
Centrum Medyczne Angelius Provita
City
Katowice
ZIP/Postal Code
40-611
Country
Poland
Facility Name
Malopolskie Centrum Medyczne s.c.
City
Krakow
ZIP/Postal Code
30-510
Country
Poland
Facility Name
Centrum Terapii Wspolczesnej J.M. Jasnorzewska sp. komandytowo-akcyjna
City
Lodz
ZIP/Postal Code
90-242
Country
Poland
Facility Name
KLIMED Marek Klimkiewicz
City
Lomza
ZIP/Postal Code
18-404
Country
Poland
Facility Name
RCMed
City
Nowy Duninow
ZIP/Postal Code
09-505
Country
Poland
Facility Name
ETYKA Osrodek Badan Klinicznych
City
Olsztyn
ZIP/Postal Code
10-117
Country
Poland
Facility Name
Niepubliczny Zaklad Opieki Zdrowotnej "Nasz Lekarz" Praktyka Grupowa Lekarzy Rodzinnych z
City
Torun
ZIP/Postal Code
87-100
Country
Poland
Facility Name
Medycyna Kliniczna
City
Warszawa
ZIP/Postal Code
00-660
Country
Poland
Facility Name
Rheuma Medicus Zaklad Opieki Zdrowotnej
City
Warszawa
ZIP/Postal Code
02-118
Country
Poland
Facility Name
Niepubliczny Zakład Opieki Zdrowotnej "Biogenes" Sp. z o.o.
City
Wroclaw
ZIP/Postal Code
53-224
Country
Poland
Facility Name
Glasgow Royal Infirmary
City
Glasgow
State/Province
Strathclyde
ZIP/Postal Code
G4 0SF
Country
United Kingdom
Facility Name
Whipps Cross University Hospital
City
London
ZIP/Postal Code
E11 1NR
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
33263165
Citation
Huizinga TWJ, Torii Y, Muniz R. Adalimumab Biosimilars in the Treatment of Rheumatoid Arthritis: A Systematic Review of the Evidence for Biosimilarity. Rheumatol Ther. 2021 Mar;8(1):41-61. doi: 10.1007/s40744-020-00259-8. Epub 2020 Dec 1.
Results Reference
derived

Learn more about this trial

MSB11022 in Moderate to Severe Rheumatoid Arthritis

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