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

• ClinicalTrials.gov Identifier: NCT03253796
• Recruitment Status: Active, not recruiting
• First Posted: August 18, 2017
• Last Update Posted: February 26, 2021
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Tracking Information

• First Submitted Date: August 16, 2017
• First Posted Date: August 18, 2017
• Last Update Posted Date: February 26, 2021
• Actual Study Start Date: November 7, 2017
• Estimated Primary Completion Date: March 26, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 16, 2017)

Disease Activity Flare [ Time Frame: Up to 12 months ]

Percentage of participants without a disease activity "flare" during up to 12 months following randomization to DB therapy

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 16, 2017)

• Clinical Response [ Time Frame: Up to 12 months ]
  Percentage of participants with a clinical response to re-treatment with OL golimumab after a "flare" in Period 2
• First Flare [ Time Frame: Up to 12 months ]
  Time to first "flare" in Period 2
• Assessment in SpondyloArthritis international Society (ASAS)20 Response [ Time Frame: Up to 12 months ]
  Percentage of participants achieving ASAS20 response (20% reduction in ASAS) in Period 2
• ASAS40 Response [ Time Frame: Up to 12 months ]
  Percentage of participants achieving ASAS40 response (40% reduction in ASAS) in Period 2
• Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)50 Response [ Time Frame: Up to 12 months ]
  Percentage of participants achieving a BASDAI50 response (250% reduction in BSDAI) in Period 2
• ASAS Partial Remission [ Time Frame: Up to 12 months ]
  Percentage of participants achieving ASAS partial remission in Period 2
• Inactive Disease Status [ Time Frame: Up to 12 months ]
  Percentage of participants achieving inactive disease status in Period 2

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: August 16, 2017)

• Adverse Events [ Time Frame: Up to 12 months, plus AE follow up ]
  Number of participants who experience at lease one adverse event (AE)
• Discontinuations [ Time Frame: Up to 12 months ]
  Number of participants who discontinue treatment due to an AE

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Golimumab (MK-8259 / SCH900259) Treatment Withdrawal in Participants With Non-radiographic Axial Spondyloarthritis (MK-8259-038)
• Official Title: 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
• Brief Summary: The purpose of this study is to evaluate the effect of treatment withdrawal vs 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

To evaluate the effect of treatment withdrawal vs 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 (Participant, Investigator)
Primary Purpose: Treatment

• Condition: Spondyloarthritis

Intervention

• Biological: Golimumab QM: Period 1 (OL)
  OL monthly injections of active golimumab 50 mg or 100 mg (two 50 mg injections) from Month 0 to Month 9 (Period 1, run-in)
  Other Name: MK-8259
• Biological: Golimumab QM: Period 2 (DB)
  DB monthly injections of active golimumab 50 mg or 100 mg (two 50 mg injections) for 12 months, or until "flare" (Period 2, full treatment)
  Other Name: MK-8259
• Biological: Golimumab Q2M: Period 2 (DB)
  DB monthly injections of golimumab 50 mg or 100 mg (two 50 mg injections), alternating with placebo, for 12 months, or until "flare" (Period 2, reduced treatment)
  Other Name: MK-8259
• Other: Placebo QM: Period 2 (DB)
  DB monthly injections of placebo for golimumab for 12 months, or until "flare" (Period 2, treatment withdrawal)
• Biological: Golimumab QM: Period 2 (OL)
  OL golimumab 50 mg or 100 mg (two 50 mg injections) for 12 months (Period 2, full treatment re-started after "flare")
  Other Name: MK-8259

Study Arms

• Experimental: Open-label (OL) GLM SC QM ---> PBO SC QM
  In Period 1 participants are treated with OL GLM SC QM; followed by Period 2 where participants are treated with placebo (PBO) SC QM
  Interventions:

  • Biological: Golimumab QM: Period 1 (OL)
  • Other: Placebo QM: Period 2 (DB)
  • Biological: Golimumab QM: Period 2 (OL)
• Experimental: OL GLM SC QM ---> DB GLM SC QM
  In Period 1 participants are treated with OL GLM SC QM; followed by Period 2 where participants are treated with double-blinded (DB) GLM SC QM
  Interventions:

  • Biological: Golimumab QM: Period 1 (OL)
  • Biological: Golimumab QM: Period 2 (DB)
• Experimental: OL GLM SC QM ---> DB GLM SC Q2M
  In Period 1 participants are treated with OL GLM SC QM; followed by Period 2 where participants are treated with DB GLM SC Q2M
  Interventions:

  • Biological: Golimumab QM: Period 1 (OL)
  • Biological: Golimumab Q2M: Period 2 (DB)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: August 16, 2017): 300
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 26, 2021
• Estimated Primary Completion Date: March 26, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 nr-axSpA with disease duration <= 5 years

• 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 CRP
  • • Human leukocyte antigen B27 (HLA-B27)+ gene
• Has a HLA-B27+ gene and 2 or more of the SpA characteristics listed above
• Has elevated CRP at Screening or evidence of active inflammation in the sacroiliac joints on MRI
• Has an 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

Exclusion Criteria:

• Has bilateral sacroiliitis Grade 2 or unilateral sacroiliitis Grade 3 or Grade 4
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Czechia, Germany, Netherlands, Poland, Romania, Russian Federation, Spain, Turkey, Ukraine
• Removed Location Countries: Bulgaria, Estonia, Ireland, Latvia, Lithuania, United Kingdom

Administrative Information

• NCT Number: NCT03253796
• Other Study ID Numbers: 8259-038; 2015-004020-65 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Responsible Party: Merck Sharp & Dohme Corp.
• Study Sponsor: Merck Sharp & Dohme Corp.
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

• PRS Account: Merck Sharp & Dohme Corp.
• Verification Date: February 2021