Golimumab (MK-8259 / SCH900259) Treatment Withdrawal in Participants With Non-radiographic Axial Spondyloarthritis (GO-BACK) (MK-8259-038)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of treatment withdrawal compared to continued treatment with golimumab (GLM) administered by subcutaneous (SC) injection on the incidence of a flare in non-radiographic axial spondyloarthritis over up to 12 months. The primary hypothesis is that continued treatment with golimumab is superior to treatment withdrawal, based on the percentage of subjects without a flare during up to 12 months of blinded therapy.

Official Title
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A Phase-IV, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Trial to Evaluate the Efficacy and Safety of Golimumab (MK-8259 [SCH 900259]) After Treatment Withdrawal, Compared With Continued Treatment (Either Full- or Reduced-Treatment Regimen), In Subjects With Non-Radiographic Axial Spondyloarthritis

Conditions
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Spondyloarthritis

Intervention / Treatment
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* Biological: Golimumab
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is not of reproductive potential, or is of reproductive potential and agrees to avoid becoming pregnant or impregnating a partner while receiving trial medication or within 6 months after the last dose of trial medication Has chronic back pain of ≥3 months duration by history Has physician-diagnosed active non-radiographic axial spondyloarthritis (nr-axSpA) with disease duration <= 5 years Meets one of the following criteria: Has active inflammation on magnetic resonance imaging (MRI) highly suggestive of sacroiliitis associated with spondyloarthropathy and 1 or more of the following spondyloarthritis (SpA) characteristics: Inflammatory back pain Arthritis (physician-diagnosed) Enthesitis (heel) physician-diagnosed (spontaneous pain or tenderness at examination of the site of the insertion of the Achilles tendon or plantar fascia) Dactylitis (physician-diagnosed) Psoriasis (physician-diagnosed) History of physician-diagnosed inflammatory bowel disease (IBD) History of uveitis confirmed by an ophthalmologist Good response to nonsteroidal anti-inflammatory drugs (NSAID) Family history of SpA (presence of ankylosing spondylitis, psoriasis, acute uveitis, reactive arthritis, or IBD) Elevated C-reactive protein (CRP) Human leukocyte antigen B27 (HLA-B27)+ gene OR Has a HLA-B27+ gene and 2 or more of the following SpA characteristics: Inflammatory back pain Arthritis (physician-diagnosed) Enthesitis (heel) physician-diagnosed (spontaneous pain or tenderness at examination of the site of the insertion of the Achilles tendon or plantar fascia) Dactylitis (physician-diagnosed) Psoriasis (physician-diagnosed) History of physician-diagnosed inflammatory bowel disease (IBD) History of uveitis confirmed by an ophthalmologist Good response to nonsteroidal anti-inflammatory drugs (NSAID) Family history of SpA (presence of ankylosing spondylitis, psoriasis, acute uveitis, reactive arthritis, or IBD) Elevated C-reactive protein (CRP) Has elevated CRP at Screening or evidence of active inflammation in the sacroiliac joints on MRI Has an Ankylosing Spondylitis Disease Activity Score (ASDAS) >= 2.1 at Screening Shows high disease activity at Screening and Baseline of both a Total Back Pain score of ≥4 and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of >= 4 Has an acceptable history of NSAID use Has no history of untreated latent or active tuberculosis (TB) prior to Screening Has had no recent close contact with a person with active TB or, if there has been such contact, will undergo additional evaluations and receive appropriate treatment for latent TB Agrees to undergo screening for hepatitis B virus (HBV) and demonstrates negative results for hepatitis B surface antigen (HBsAg) and HBV deoxyribonucleic acid (DNA) Exclusion Criteria: Has bilateral sacroiliitis Grade 2 or unilateral sacroiliitis Grade 3 or Grade 4 on conventional x-rays Is a nursing or pregnant female, or intends to become pregnant within 6 months after receiving trial medication Intends to donate eggs (female participants) or sperm (male participants) while receiving trial medication or within 6 months after trial medication Has any clinically significant condition or situation that would interfere with the trial evaluations or participation in the trial Has ever received any cytotoxic drugs, including chlorambucil, cyclophosphamide, nitrogen mustard, or other alkylating agents Has received any treatment listed below more recently than the indicated off-drug period prior to Screening • Disease-modifying anti-rheumatic drugs (30 days off drug) • Live vaccinations (3 months off drug) • Investigational medications (30 days or 5 half-lives off drug, whichever is longer) • Bacille Calmette-Guerin (BCG) vaccination (12 months off drug) Has any systemic inflammatory condition, including psoriatic arthritis, active Lyme disease, systemic lupus erythematosus, infectious arthritis, vasculitis, parvovirus infection, rheumatoid arthritis, active uveitis, or active IBD Has a history of latent or active granulomatous infection prior to Screening Had a nontuberculous mycobacterial infection or opportunistic infection within 6 months prior to Screening Has a history of an infected joint prosthesis, or has received antibiotics for a suspected infection of a joint prosthesis, if that prosthesis has not been removed or replaced Had a serious infection, has been hospitalized for an infection, or has been treated with IV antibiotics for an infection within 2 months prior to Baseline Had a history of, or ongoing, chronic or recurrent infectious disease Is known to be infected with human immunodeficiency virus (HIV) or seropositive for hepatitis C virus (HCV) Has had a chest x-ray within 2 months prior to Screening that shows an abnormality suggestive of a current active infection or malignancy Has a history of lymphoproliferative disease Has had a malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of cervix that has been surgically cured) Has a history of known demyelinating diseases such as multiple sclerosis or optic neuritis Has a history of or concurrent congestive heart failure of any grade Has a transplanted organ (with the exception of a corneal transplant performed >= 3 months prior to baseline) Has current signs or symptoms of significant medical illness which could interfere with the trial, or require treatment that might interfere with the trial Is a user of recreational or illicit drugs or has or had a substance abuse (drug or alcohol) problem within the previous 2 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: To evaluate the effect of treatment withdrawal compared to continued treatment with golimumab (either every month [QM] or every 2 months [Q2M]) on the incidence of a flare during up to 12 months in Period 2 (blinded therapy).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLM SC QM (Full Treatment Regimen)<br>Period 1: participants are treated with open-label (OL) GLM SC QM for up to 10 months; Period 2: participants are treated with double-blinded SC GLM QM for up to 12 months | Biological: Golimumab<br>* Injections of 50 mg golimumab. At the investigator's discretion, participants with a body weight of more than 100 kg could receive 100 mg injections with golimumab.<br>* Other names: Simponi®;|
| Experimental: GLM SC Q2M (Reduced Treatment Regimen)<br>Period 1: participants are treated with OL GLM SC QM for up to 10 months; Period 2: participants are treated with double-blinded GLM SC every other month alternating with matching placebo to GLM every other month for up to 12 months | Biological: Golimumab<br>* Injections of 50 mg golimumab. At the investigator's discretion, participants with a body weight of more than 100 kg could receive 100 mg injections with golimumab.<br>* Other names: Simponi®;Biological: Placebo<br>* Injections of matching placebo for golimumab.<br>|
| Placebo Comparator: Placebo (Treatment Withdrawal Regimen)<br>Period 1: participants are treated with OL GLM SC QM for up to 10 months; Period 2: participants are treated with double-blinded placebo for up to 12 months | Biological: Golimumab<br>* Injections of 50 mg golimumab. At the investigator's discretion, participants with a body weight of more than 100 kg could receive 100 mg injections with golimumab.<br>* Other names: Simponi®;Biological: Placebo<br>* Injections of matching placebo for golimumab.<br>|
| Experimental: OL GLM Retreatment<br>Participants who experience a disease flare during double-blinded treatment in Period 2 will discontinue blinded treatment and receive OL GLM SC QM. | Biological: Golimumab<br>* Injections of 50 mg golimumab. At the investigator's discretion, participants with a body weight of more than 100 kg could receive 100 mg injections with golimumab.<br>* Other names: Simponi®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Without a Disease Activity Flare During Period 2 | Disease flare is defined as an Ankylosing Spondylitis Disease Activity Score (ASDAS) at two consecutive visits that both show either absolute score ≥2.1 or a post-withdrawal increase of ≥1.1 relative to baseline prior to the first dose of double-blind treatment in Period 2. The ASDAS is a composite index assessing disease activity in axial spondyloarthropathies that consists of 4 self-assessed parameters and 1 laboratory parameter. The self-assessed parameters of back pain, duration of morning stiffness, Patient Global Disease Assessment (PGDn), and peripheral pain/swelling are individually scored on a numeric scale of 0 to 10, with 0 being low activity/impact and 10 being high activity/impact. The self-assessed criteria and the laboratory value of CRP are combined to provide the total ASDAS score, which has a lower limit of 0.6 and no defined upper limit. A higher score indicates greater disease activity. | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Flare Who Show a Clinical Response Within 3 Months of Open-Label Golimumab Retreatment | Clinical response is defined as Bath Ankylosing Spondylitis Disease Assessment Index (BASDAI) score improvement of ≥2.0 or ≥50% improvement within 3 months of the start of retreatment, relative to the mean of the two consecutive BASDAI scores that defined the flare. Sustained clinical response refers to participants who attained clinical response and maintained BASDAI criteria throughout the 3-month retreatment period. Response data was collected throughout Period 2 (12 months) and censored to include only the first 3 months after retreatment for a disease flare. The BASDAI is a summary of 6 participant-assessed measures rated on scales of 0 (none) to 10 (very severe): fatigue, spinal pain, joint pain/swelling, tenderness, morning stiffness, and duration of morning stiffness [0 (zero) to 10 (2 or more hours)]. The BASDAI score is the mean of responses to the 6 questions with a minimum of 0 and a maximum of 10. A higher score indicates greater disease activity. | Up to 3 months following start of retreatment | 
| Time to First Disease Flare | The Kaplan-Meier analysis of time to first flare in Period 2 is represented by the percentage of participants who experienced a disease flare relative to baseline prior to the first dose of double-blind treatment in Period 2. Disease flare is defined as ASDAS at two consecutive visits that both show either absolute score ≥2.1 or a post-withdrawal increase of ≥1.1. | Month 3, Month 6, Month 9, and Month 12 | 
| Percentage of Participants Achieving ASAS20 (Assessment in SpondyloArthritis International Society) Response (Double-blind Treatment) | ASAS20 is a 20% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of ≥20% from Baseline and an absolute improvement from Baseline of ≥1.0 in at least 3 of 4 domains, and 2) Absence of deterioration from Baseline (defined as a ≥20% worsening and an absolute worsening of ≥1.0) in the potential remaining domain. Baseline for ASAS20 analysis is defined as the last ASAS score prior to the first dose of double-blind treatment in Period 2. The ASAS consists of 4 domains: the Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index [BASFI]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment. | Up to 12 months | 
| Percentage of Participants Achieving ASAS20 Response (Open-label Retreatment) | ASAS20 is a 20% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of ≥20% from Baseline and an absolute improvement from Baseline of ≥1.0 in at least 3 of 4 domains, and 2) Absence of deterioration from Baseline (defined as a ≥20% worsening and an absolute worsening of ≥1.0) in the potential remaining domain. Baseline for ASAS20 analysis is defined as the last ASAS score prior to the first dose of open-label retreatment in Period 2. The ASAS consists of 4 domains: the Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index [BASFI]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment. | Up to 12 months | 
| Percentage of Participants Achieving ASAS40 Response (Double-blind Treatment) | ASAS40 is a 40% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of ≥40% from Baseline and an absolute improvement from Baseline of ≥2.0 in at least 3 of 4 domains, and 2) No deterioration from Baseline in the potential remaining domain. Baseline for ASAS40 analysis is defined as the last ASAS score prior to the first dose of double-blind treatment in Period 2. The ASAS consists of 4 domains: the Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index [BASFI]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment. | Up to 12 months | 
| Percentage of Participants Achieving ASAS40 Response (Open-label Retreatment) | ASAS40 is a 40% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of ≥40% from Baseline and an absolute improvement from Baseline of ≥2.0 in at least 3 of 4 domains, and 2) No deterioration from Baseline in the potential remaining domain. Baseline for ASAS40 analysis is defined as the last ASAS score prior to the first dose of open-label retreatment in Period 2. The ASAS consists of 4 domains: the Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index [BASFI]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment. | Up to 12 months | 
| Percentage of Participants Achieving ASAS Partial Remission (Double-blind Treatment) | ASAS partial remission is defined as a score of ≤2 in all 4 ASAS domains. Baseline for this analysis is defined as the ASAS score prior to the first dose of double-blind treatment in Period 2. The ASAS consists of 4 domains: Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index [BASFI]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment. | Up to 12 months | 
| Percentage of Participants Achieving ASAS Partial Remission (Open-label Retreatment) | ASAS partial remission is defined as a score of ≤2 in all 4 ASAS domains. Baseline for this analysis is defined as the ASAS score prior to the first dose of open-label retreatment in Period 2. The ASAS consists of 4 domains: Patient Global Disease Assessment (PGDn), total back pain, function (Bath Ankylosing Spondylitis Functional Index [BASFI]), and morning stiffness (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]). Each domain is measured on a 10-point numeric scale from 0=no disease symptoms/impact to 10=extreme disease symptoms/impact, with a higher score indicating more severe impairment. | Up to 12 months | 
| Percentage of Participants Achieving BASDAI50 Response (Double-blind Treatment) | BASDAI50 is defined as ≥50% improvement from baseline in the Bath Ankylosing Spondylitis Disease Assessment Index (BASDAI) score. Baseline for BASDAI50 analysis is defined as the last BASDAI score prior to the first dose of double-blind treatment in Period 2. The BASDAI is a summary of 6 participant-assessed measures rated on scales of 0 (none) to 10 (very severe): fatigue, spinal pain, joint pain/swelling, tenderness, morning stiffness, and duration of morning stiffness [0 (zero) to 10 (2 or more hours)]. The BASDAI score is the mean of responses to the 6 questions with a minimum of 0 and a maximum of 10. A higher score indicates greater disease activity. | Up to 12 months | 
| Percentage of Participants Achieving BASDAI50 Response (Open-label Retreatment) | BASDAI50 is defined as ≥50% improvement from baseline in the Bath Ankylosing Spondylitis Disease Assessment Index (BASDAI) score. Baseline for BASDAI50 analysis is defined as the last BASDAI score prior to the first dose of open-label retreatment in Period 2. The BASDAI is a summary of 6 participant-assessed measures rated on scales of 0 (none) to 10 (very severe): fatigue, spinal pain, joint pain/swelling, tenderness, morning stiffness, and duration of morning stiffness [0 (zero) to 10 (2 or more hours)]. The BASDAI score is the mean of responses to the 6 questions with a minimum of 0 and a maximum of 10. A higher score indicates greater disease activity. | Up to 12 months | 
| Percentage of Participants Achieving Inactive Disease Status (Double-Blind Treatment) | Inactive disease status is defined as an ASDAS score <1.3. The ASDAS is a composite index assessing disease activity in axial spondyloarthropathies that consists of 4 self-assessed parameters and 1 laboratory parameter. The self-assessed parameters of back pain, duration of morning stiffness, Patient Global Disease Assessment (PGDn), and peripheral pain/swelling are individually scored on a numeric scale of 0 to 10, with 0 being low activity/impact and 10 being high activity/impact. The self-assessed criteria and the laboratory value of CRP are combined to provide the total ASDAS score, which has a lower limit of 0.6 and no defined upper limit. A higher score indicates greater disease activity. | Up to 12 months | 
| Percentage of Participants Achieving Inactive Disease Status (Open-label Retreatment) | Inactive disease status is defined as an ASDAS score <1.3. The ASDAS is a composite index assessing disease activity in axial spondyloarthropathies that consists of 4 self-assessed parameters and 1 laboratory parameter. The self-assessed parameters of back pain, duration of morning stiffness, Patient Global Disease Assessment (PGDn), and peripheral pain/swelling are individually scored on a numeric scale of 0 to 10, with 0 being low activity/impact and 10 being high activity/impact. The self-assessed criteria and the laboratory value of CRP are combined to provide the total ASDAS score, which has a lower limit of 0.6 and no defined upper limit. A higher score indicates greater disease activity. | Up to 12 months | 
| Percentage of Participants Who Experienced an Adverse Event (AE) in Period 2 | This endpoint evaluated the safety and tolerability of withdrawing from or continuing treatment with golimumab in Period 2. An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of study treatment, is also an AE. The analysis includes AEs that occurred through 90 days after the last dose of study treatment. | Up to approximately 15 months | 
| Percentage of Participants Who Discontinued Study Treatment Due to an AE in Period 2 | This endpoint evaluated the safety and tolerability of withdrawing from or continuing treatment with golimumab in Period 2. An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of study treatment, is also an AE. | Up to approximately 12 months |