Clinical trial NCT03253796: Golimumab (MK-8259 / SCH900259) Treatment Withdrawal in Participants With Non-radiographic Axial Spondyloarthritis (GO-BACK) (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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Spondyloarthritis
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-08-18
Enrollment: 323
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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).
Primary purpose: TREATMENT

Brief summary: 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.


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 non-radiographic axial spondyloarthritis (nr-axSpA) with disease duration \<= 5 years
* Meets one of the following criteria:

  1. 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
  2. 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

Primary outcomes:
measure: Percentage of Participants Without a Disease Activity Flare During Period 2
timeFrame: Up to 12 months
Secondary outcomes:
measure: Percentage of Participants With a Flare Who Show a Clinical Response Within 3 Months of Open-Label Golimumab Retreatment
timeFrame: Up to 3 months following start of retreatment
measure: Time to First Disease Flare
timeFrame: Month 3, Month 6, Month 9, and Month 12
measure: Percentage of Participants Achieving ASAS20 (Assessment in SpondyloArthritis International Society) Response (Double-blind Treatment)
timeFrame: Up to 12 months
measure: Percentage of Participants Achieving ASAS20 Response (Open-label Retreatment)
timeFrame: Up to 12 months
measure: Percentage of Participants Achieving ASAS40 Response (Double-blind Treatment)
timeFrame: Up to 12 months
measure: Percentage of Participants Achieving ASAS40 Response (Open-label Retreatment)
timeFrame: Up to 12 months
measure: Percentage of Participants Achieving ASAS Partial Remission (Double-blind Treatment)
timeFrame: Up to 12 months
measure: Percentage of Participants Achieving ASAS Partial Remission (Open-label Retreatment)
timeFrame: Up to 12 months
measure: Percentage of Participants Achieving BASDAI50 Response (Double-blind Treatment)
timeFrame: Up to 12 months
measure: Percentage of Participants Achieving BASDAI50 Response (Open-label Retreatment)
timeFrame: Up to 12 months
measure: Percentage of Participants Achieving Inactive Disease Status (Double-Blind Treatment)
timeFrame: Up to 12 months
measure: Percentage of Participants Achieving Inactive Disease Status (Open-label Retreatment)
timeFrame: Up to 12 months
measure: Percentage of Participants Who Experienced an Adverse Event (AE) in Period 2
timeFrame: Up to approximately 15 months
measure: Percentage of Participants Who Discontinued Study Treatment Due to an AE in Period 2
timeFrame: Up to approximately 12 months
Other outcomes:
measure: Percentage of Participants Without a Disease Activity Flare During Period 2 (Full Treatment Regimen Versus Withdrawal Regimens)
timeFrame: Up to 12 months
measure: Percentage of Participants Without a Disease Activity Flare During Period 2 (Full Treatment Regimen Versus Reduced Treatment Regimen)
timeFrame: Up to 12 months
Locations:
city: Brno
country: Czechia
facility: FN Brno ( Site 0005)
city: Brno
country: Czechia
facility: Revmatologie s.r.o. ( Site 0009)
city: Ostrava-Trebovice
country: Czechia
facility: Artroscan s.r.o. ( Site 0007)
city: Ostrava
country: Czechia
facility: CCBR Ostrava s.r.o. ( Site 0001)
city: Pardubice
country: Czechia
facility: CCR Czech a.s. ( Site 0003)
city: Praha
country: Czechia
facility: CCR Prague s.r.o ( Site 0004)
city: Praha
country: Czechia
facility: Fakultni nemocnice v Motole ( Site 0127)
city: Uherske Hradiste
country: Czechia
facility: Medical Plus s.r.o ( Site 0010)
city: Zlin
country: Czechia
facility: PV - Medical s.r.o. ( Site 0006)
city: Berlin
country: Germany
facility: Universitaetsklinik der Charite Berlin ( Site 0023)
city: Herne
country: Germany
facility: Rheumazentrum Ruhrgebiet ( Site 0021)
city: Koeln
country: Germany
facility: U. klinikum Koeln AOER ( Site 0025)
city: Muenchen
country: Germany
facility: Klinikum der Universitaet Muenchen - LMU ( Site 0026)
city: Muenchen
country: Germany
facility: Herbert Kellner Innere Medizin Rheumatologie und Gastroenterologie ( Site 0022)
city: Sneek
country: Netherlands
facility: Antonius Ziekenhuis Sneek ( Site 0043)
state: Friesland
city: Amsterdam
country: Netherlands
facility: Vrij Universiteit Medisch Centrum ( Site 0044)
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum ( Site 0041)
city: Rotterdam
country: Netherlands
facility: Maasstad Ziekenhuis ( Site 0042)
city: Katowice
country: Poland
facility: Centrum Medyczne Pratia Katowice ( Site 0059)
state: Slaskie
city: Poznan
country: Poland
facility: Prywatna Praktyka Lekarska, Dr. med. Pawel Hrycaj ( Site 0060)
state: Wielkopolskie
city: Bialystok
country: Poland
facility: NZOZ Osteo-Medic s.c. A. Racewicz, R. Supronik ( Site 0058)
city: Bydgoszcz
country: Poland
facility: Klinika Reumatologii i Ukladowych Chorob Tkanki Lacznej ( Site 0153)
city: Elblag
country: Poland
facility: Centrum Kliniczno-Badawcze ( Site 0152)
city: Krakow
country: Poland
facility: Krakow Medical Centre ( Site 0052)
city: Lublin
country: Poland
facility: NZOZ Reumed ( Site 0051)
city: Sopot
country: Poland
facility: Pomorskie Cent. Reumatologiczne IM.Dr. Titz-Kosko W Sopocie Sp. Z.o.o. ( Site 0057)
city: Swidnik
country: Poland
facility: Lubelskie Centrum Diagnostyczne ( Site 0053)
city: Torun
country: Poland
facility: NZOZ Nasz Lekarz Praktyka Grupowa Lekarzy Rodzinnych ( Site 0151)
city: Warszawa
country: Poland
facility: Reumatika ( Site 0055)
city: Brasov
country: Romania
facility: Centrul Medical de Diagnostic si Tratament Ambulator Neomed ( Site 0177)
city: Bucaresti
country: Romania
facility: Clinical Hospital Ioan Cantacuzino ( Site 0184)
city: Bucarest
country: Romania
facility: Colentina Clinical Hospital ( Site 0231)
city: Bucharest
country: Romania
facility: Spitalul Clinic Sfanta Maria ( Site 0182)
city: Bucuresti
country: Romania
facility: SC Duo Medical SRL ( Site 0183)
city: Cluj Napoca
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Cluj-Napoca ( Site 0176)
city: Iasi
country: Romania
facility: RKMed Center ( Site 0180)
city: Oradea
country: Romania
facility: S.C.Pelican Impex S.R.L ( Site 0232)
city: Sfantu Gheorghe
country: Romania
facility: Covamed Serv SRL ( Site 0178)
city: Timisoara
country: Romania
facility: Cabinet Medical Medicina Interna Dr. Triff Carina ( Site 0179)
city: Saratov
country: Russian Federation
facility: GUZ Regional Clinical Hospital ( Site 0076)
state: Oktyabrskiy Region
city: Moscow
country: Russian Federation
facility: Rheumatology Research Institute n.a. V.A.Nasonova of RAMS ( Site 0061)
city: Saint Petersburg
country: Russian Federation
facility: SPb SBHI Clinical Rheumatological Hospital 25 ( Site 0077)
city: Saint Petersburg
country: Russian Federation
facility: SBHI Leningrad Regional Clinical Hospital ( Site 0065)
city: Saint-Petersburg
country: Russian Federation
facility: LLC Sanavita ( Site 0074)
city: Tolyatti
country: Russian Federation
facility: Tolyatti City Clinical Hospital 5 ( Site 0069)
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl Clinical Hospital for Emergency Care na. NV. Solovyev. ( Site 0075)
city: Bilbao
country: Spain
facility: Hospital de Basurto ( Site 0082)
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia ( Site 0081)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz ( Site 0083)
city: Murcia
country: Spain
facility: Hospital Clinico Universitario Virgen de la Arrixaca ( Site 0085)
city: Antalya
country: Turkey
facility: Akdeniz Universitesi Tip Fakultesi Romatoloji Departmani ( Site 0094)
state: Ankara
city: Ankara
country: Turkey
facility: Ankara Numune Egitim Arastirma Hastanesi ( Site 0092)
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 0091)
city: Ankara
country: Turkey
facility: Ankara Universitesi Tıp Fakultesi ( Site 0093)
city: Denizli
country: Turkey
facility: Pamukkale Unv. Tip Fak. ( Site 0097)
city: Istanbul
country: Turkey
facility: Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 0098)
city: Kocaeli
country: Turkey
facility: Kocaeli Universitesi Tip Fakultesi Ic Hastaliklari ( Site 0096)
city: Cherkassy
country: Ukraine
facility: Cherkassy Regional hospital of Cherkassy Regional council ( Site 0221)
city: Dnipropetrovsk
country: Ukraine
facility: MI Dnipr Regional Clinical Hospital named after I.I. Mechnikov ( Site 0222)
city: Kharkiv
country: Ukraine
facility: SI National Institute of therapy n.a L.T. Maloi NAMS of Ukraine ( Site 0261)
city: Kharkiv
country: Ukraine
facility: ME of Health Care Kharkiv City Clinical Hospital #8 ( Site 0262)
city: Kyiv
country: Ukraine
facility: Kyivska miska klinichna likarnia N3 ( Site 0266)
city: Kyiv
country: Ukraine
facility: M. D. Strazhesko Institute of Cardiology. ( Site 0264)
city: Kyiv
country: Ukraine
facility: Medical Center Ibn Sina ( Site 0268)
city: Kyiv
country: Ukraine
facility: Clinic of Modern Rheumatology ( Site 0265)
city: Lviv
country: Ukraine
facility: Communal City Clinical Hospital #4 ( Site 0230)
city: Odesa
country: Ukraine
facility: MI Odesa Regional Clinical Hospital ( Site 0226)
city: Poltava
country: Ukraine
facility: M.V.Sklifosovskyi Poltava Regional Clinical Hospital ( Site 0224)
city: Vinnutsya
country: Ukraine
facility: Vinnitsa Regional Clinical Hospital n.a. Pirogov ( Site 0225)
city: Vinnytsia
country: Ukraine
facility: SRI of Invalid Rehabilitation of Vinnytsia M.I.Pyrogov ( Site 0263)
city: Zaporizhzhya
country: Ukraine
facility: Zaporizhzha Regional Clinical Hospital ( Site 0223)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Weinstein CLJ, Sliwinska-Stanczyk P, Hala T, Stanislav M, Tzontcheva A, Yao R, Berd Y, Curtis SP, Philip G. Efficacy and safety of golimumab in patients with non-radiographic axial spondyloarthritis: a withdrawal and retreatment study (GO-BACK). Rheumatology (Oxford). 2023 Nov 2;62(11):3601-3609. doi: 10.1093/rheumatology/kead112.