A Study of Golimumab in Participants With Active Ankylosing Spondylitis

A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, an Anti-TNFα Monoclonal Antibody, Administered Intravenously, in Subjects With Active Ankylosing Spondylitis

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02186873

Enrollment

208

Registered

2014-07-10

Start date

2014-09-03

Completion date

2016-10-11

Last updated

2025-10-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Ankylosing Spondylitis

Keywords

Ankylosing Spondylitis, Golimumab, SIMPONI

Brief summary

The purpose of this study is to evaluate the efficacy of intravenously (administration of a fluid into the vein) administered golimumab 2 milligram per kilogram (mg/kg) in participants with active ankylosing spondylitis (chronic inflammatory disease of unknown etiology that involves the sacroiliac joints, and often the axial skeleton, entheses, and peripheral joints).

Detailed description

This is a Phase 3, multicenter (when more than one hospital or medical school team work on a medical research study), randomized (study drug assigned by chance), double-blind (neither the researchers nor the participants know what treatment the participant is receiving), placebo-controlled (an inactive substance; a pretend treatment \[with no drug in it\] that is compared in a clinical trial with a drug to test if the drug has a real effect) study of golimumab compared with placebo in participants with active ankylosing spondylitis. The study comprises of 4 phases: Screening phase (up to 6 weeks), Double-blind placebo-controlled phase (Week 0 to Week 16), Active treatment phase (Week 16 to Week 52), and Safety follow-up phase (8 weeks from last study drug administration). Total duration of the study will be 60 weeks per participant. Eligible Participants will be randomly assigned to either Treatment group 1: Placebo or Treatment group 2: Golimumab. Participants randomized to Placebo group, will receive intravenous infusions of placebo at Weeks 0, 4 and 12. At Week 16, all participants receiving placebo will begin receiving intravenous infusions of golimumab (2 mg/kg) at Weeks 16, 20 and thereafter every 8 weeks up to Week 52. Participants randomized to Golimumab group, will receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and thereafter every 8 weeks up to Week 52. At Week 16, participants randomized to golimumab group will receive a placebo infusion to maintain the blind. The efficacy will be assessed primarily by measuring percentage of participants who achieve a 20 percent improvement from baseline in the assessment in ankylosing spondylitis (ASAS) at Week 16. Participant's safety will be monitored throughout the study.

Interventions

DRUGPlacebo

Participants will receive matching placebo.

DRUGGolimumab

Participants will receive 2mg/kg of intravenous infusions of golimumab .

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Participants with diagnosis of definite ankylosing spondylitis for at least 3 months based on modified New York radiographic and clinical criteria * Participants with symptoms of active disease at screening and at baseline * Participant has either an inadequate response to at least 2 non-steroidal anti-inflammatory drugs (NSAID) over a 4 week period in total with maximal recommended doses of NSAIDs, or is unable to receive a full 4 weeks of maximal NSAID therapy because of intolerance, toxicity, or contraindications to NSAIDs * Participants with C- reactive protein (CRP) level of greater than or equal to (\>=) 0.3 milligram per deciliter (mg/dL) at screening * Additional protocol-defined inclusion criteria apply

Exclusion criteria

* Participant with other inflammatory diseases that might confound the evaluations of benefit from the golimumab therapy * Pregnant or lactating females * Participants with chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection, including tuberculosis * Participants who had a serious infection (including but not limited to, hepatitis, pneumonia, sepsis, or pyelonephritis), or have been hospitalized for an infection, or have been treated with intravenous (IV) antibiotics for an infection within 2 months prior to first administration of study agent * Additional protocol-defined

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Who Achieved at Least 20 Percent Improvement From Baseline in the Assessment of SpondyloArthritis International Society (ASAS 20) at Week 16	Week 16	ASAS 20 defined as 20 percent (%) improvement compared to baseline in the ASAS Working Group criteria: that is, greater than or equal to (\>=)20% improvement from baseline in at least 3 of the 4 domains: patient's global assessment of disease activity (0=very well,10 =very poor), total back pain (0=no pain,10=most severe pain), function (self-assessment using BASFI \[0=no functional impairment to 10= maximal impairment\]), inflammation (0=none,10=very severe) with an absolute improvement of at least 1 (0-10 centimeter (cm) visual analogue scale \[VAS\]), and an absence of deterioration (defined as \>=20% worsening and absolute worsening of at least 1 on a 0-10 cm scale) in the potential remaining domain.

Secondary

Measure	Time frame	Description
Percentage of Participants Who Achieved at Least 50 Percent Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 16	Week 16	The BASDAI is a self-assessment tool to determine disease activity using a VAS of 0-10 cm (0=none and 10=very severe) participant's answered 6 questions measuring fatigue, spinal pain, joint pain, enthesitis, and morning stiffness. The final BASDAI is calculated as a mean of individual questions with a final score range of 0 to 10 cm; 0=best and 10=worst.
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Score at Week 16	Baseline and Week 16	The BASFI is a participant's self-assessment of physical function represented as a mean of 10 questions, each question rated on VAS 0 to 10 cm (VAS 0 to 10 cm; 0=easy to 10=impossible), 8 of which relate to the participant's functional anatomy and 2 of which relate to a participant's ability to cope with everyday life.
Change From Baseline in Short Form-36 Health Survey (SF-36) Physical Component Summary (PCS) Score at Week 16	Baseline and Week 16	The Medical Outcome Study health measure SF-36 questionnaire is a well-validated and widely used quality-of-life instrument. It is a self-administered survey that consists of 8 multi-item scales: The 4 subscales of the SF-36 comprises the PCS score (physical functioning, role-physical, bodily pain, and general health) and the 4 subscales of the SF-36 comprises the MCS score (vitality, social functioning, role-emotional, and mental health). PCS and MCS are scored from 0 to 100 with higher scores indicating better health (worst value is 0 and best value is 100), which are scored using a norm-based system where linear transformations are performed to transform scores to a mean of 50 and standard deviation of 10.
Percentage of Participants Who Achieved at Least 40 Percent Improvement From Baseline in the Assessment of SpondyloArthritis International Society (ASAS 40) at Week 16	Week 16	An ASAS 40 response is defined as \>=40% improvement from baseline in 3 of 4 domains: patient's global assessment of disease activity (0=very well, 10=very poor), total back pain (0=no pain, 10=most severe pain), function (self-assessment using BASFI (0=no functional impairment to 10=maximal impairment), inflammation (0=none, 10=very severe) with an absolute improvement of at least 2 (0-10 cm VAS), and no deterioration in the remaining domain.
Percentage of Participants With Low Level of Disease Activity (ASAS Partial Remission) at Week 16	Week 16	Low level of disease activity was measured by criteria for ASAS partial remission, defined as a value below 2 on a scale of 0 to 10 cm in each of the 4 ASAS domains: patient's global assessment of disease activity, total back pain, function (BASFI), inflammation.
Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 16	Baseline and Week 16	The ASQoL is a self-administered health-related quality of life (HRQOL) instrument. It consists of 18 items requesting a Yes or No response to questions related to the impact of the disease/condition (including pain) on sleep, mood, motivation, ability to cope, activities of daily living, independence, relationships, and social life. A score of 1 is given to a response of yes on each item and all item scores are summed to a total score with a range of 0 to 18. Higher scores indicate worse HRQOL.
Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 16	Baseline and Week 16	BASMI is an objective measure of spinal mobility. The BASMI score is composed of 5 measures: tragus to wall distance, lumbar flexion, cervical rotation, lumbar side flexion, and intermalleolar distance. Each measure was scored 0-2 (0=normal mobility/mild disease involvement, 1=moderate disease involvement, 2=severe disease involvement) to give a final total BASMI score ranging from 0 to 10. The higher the BASMI score, the more severe was the participant's limitation of movement due to their AS.
Change From Baseline in Short Form-36 Health Survey (SF-36) Mental Component Summary (MCS) Score at Week 16	Baseline and Week 16	The Medical Outcome Study health measure SF-36 questionnaire is a well-validated and widely used quality-of-life instrument. It is a self-administered survey that consists of 8 multi-item scales: The 4 subscales of the SF-36 comprises the PCS score (physical functioning, role-physical, bodily pain, and general health) and the 4 subscales of the SF-36 comprises the MCS score(vitality, social functioning, role-emotional, and mental health). PCS and MCS are scored from 0 to 100 with higher scores indicating better health (worst value is 0 and best value is 100), which are scored using a norm-based system where linear transformations are performed to transform scores to a mean of 50 and standard deviation of 10.

Countries

Australia, Canada, Germany, Mexico, Poland, Russia, South Korea, Ukraine, United States

Participant flow

Pre-assignment details

Of the 312 participants screened, 208 participants were randomized (105 to golimumab 2 milligram per kilogram \[mg/kg\] and 103 to placebo group) and treated.

Participants by arm

Arm	Count
Group 1: Placebo Then Golimumab Participants received placebo intravenous (IV) infusions at Weeks 0, 4, and 12. At Week 16 participants were crossed over to golimumab and received IV golimumab 2 mg/kg infusions at Weeks 16, 20, and every 8 weeks (q8w) thereafter through Week 52.	103
Group 2: Golimumab Participants received IV golimumab 2 mg/kg infusion at Weeks 0, 4 and then q8w thereafter through Week 52. Participants received a placebo infusion at Week 16 to maintain the treatment blind.	105
Total	208

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	3
Overall Study	Lack of Efficacy	0	1
Overall Study	Lost to Follow-up	1	2
Overall Study	Withdrawal by Subject	7	2

Baseline characteristics

Characteristic	Group 1: Placebo Then Golimumab	Group 2: Golimumab	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	1 Participants	0 Participants	1 Participants
Age, Categorical Between 18 and 65 years	102 Participants	105 Participants	207 Participants
Age, Continuous	39.2 years STANDARD_DEVIATION 10.75	38.4 years STANDARD_DEVIATION 10.11	38.8 years STANDARD_DEVIATION 10.41
Region of Enrollment Canada	1 participants	1 participants	2 participants
Region of Enrollment Germany	3 participants	5 participants	8 participants
Region of Enrollment Mexico	3 participants	3 participants	6 participants
Region of Enrollment Poland	38 participants	30 participants	68 participants
Region of Enrollment Russian Federation	16 participants	14 participants	30 participants
Region of Enrollment South Korea	8 participants	10 participants	18 participants
Region of Enrollment Ukraine	25 participants	34 participants	59 participants
Region of Enrollment United States	9 participants	8 participants	17 participants
Sex: Female, Male Female	26 Participants	19 Participants	45 Participants
Sex: Female, Male Male	77 Participants	86 Participants	163 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	3 / 103	16 / 99	32 / 105
serious Total, serious adverse events	0 / 103	1 / 99	6 / 105

Outcome results

Primary

Percentage of Participants Who Achieved at Least 20 Percent Improvement From Baseline in the Assessment of SpondyloArthritis International Society (ASAS 20) at Week 16

ASAS 20 defined as 20 percent (%) improvement compared to baseline in the ASAS Working Group criteria: that is, greater than or equal to (\>=)20% improvement from baseline in at least 3 of the 4 domains: patient's global assessment of disease activity (0=very well,10 =very poor), total back pain (0=no pain,10=most severe pain), function (self-assessment using BASFI \[0=no functional impairment to 10= maximal impairment\]), inflammation (0=none,10=very severe) with an absolute improvement of at least 1 (0-10 centimeter (cm) visual analogue scale \[VAS\]), and an absence of deterioration (defined as \>=20% worsening and absolute worsening of at least 1 on a 0-10 cm scale) in the potential remaining domain.

Time frame: Week 16

Population: The full analysis set (FAS) included all participants who were randomized in the study.

Arm	Measure	Value (NUMBER)
Group 1: Placebo Then Golimumab	Percentage of Participants Who Achieved at Least 20 Percent Improvement From Baseline in the Assessment of SpondyloArthritis International Society (ASAS 20) at Week 16	26.2 Percentage of Participants
Group 2: Golimumab	Percentage of Participants Who Achieved at Least 20 Percent Improvement From Baseline in the Assessment of SpondyloArthritis International Society (ASAS 20) at Week 16	73.3 Percentage of Participants

p-value: <0.00195% CI: [35.18, 58.99]Cochran-Mantel-Haenszel

Secondary

Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 16

The ASQoL is a self-administered health-related quality of life (HRQOL) instrument. It consists of 18 items requesting a Yes or No response to questions related to the impact of the disease/condition (including pain) on sleep, mood, motivation, ability to cope, activities of daily living, independence, relationships, and social life. A score of 1 is given to a response of yes on each item and all item scores are summed to a total score with a range of 0 to 18. Higher scores indicate worse HRQOL.