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
- axiale spondyloarthritis.rheumatic disease10003816
- Registration Number
- NL-OMON47719
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 13
1.Be male or female and must be >= 18 to <= 45 years of age;2.Be able to provide written informed consent for the trial and may also provide consent for Future Biomedical Research. However, the subject may participate in the trial without participating in Future Biomedical Research;3. Meet one of the following categories:;a) The subject is not of reproductive potential, defined as a male who has azoospermia OR as a female who is either: (1)Postmenopausal (2) has had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion; OR (3) has a congenital or acquired condition that prevents childbearing.;b) The subject is a female or a male who 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 by complying with one of the following: (1) practice abstinence* from heterosexual activity OR (2) use (or have their partner use) acceptable contraception during heterosexual activity.;Acceptable methods of contraception are defined in the protocol.;4.Have chronic back pain of >=3 months duration by history;5.Have a physician*s diagnosis of active nr-axSpA with disease duration <=5 years;6.Meet either criterion *a* or *b* as adopted from ASAS classification criteria: a)Active inflammation on MRI highly suggestive of sacroiliitis associated with spondyloarthropathy and 1 or more of the spondyloarthritis;characteristics as described in the protocol. b)HLA-B27+ gene and 2 or more of the spondyloarthritis characteristics as described in the protocol;7.Have elevated CRP at the Screening visit or evidence of active inflammation in the SI joints on MRI;8.Have ASDAS >=2.1 at the Screening visit;9.Show high disease activity at Screening and Baseline of both a Total Back Pain score of >=4 and a BASDAI score of >=4 (each on a NRS of 0 to 10);10.Have an acceptable history of use of NSAIDs: either an inadequate response, as assessed by the investigator, with maximal recommended daily doses of at least 2 NSAIDs; or must be unable to receive maximal NSAID therapy because of intolerance, toxicity, or contraindications to NSAIDs. (Note: It is possible that a subject had a good response initially to NSAIDs but subsequently had inadequate response or developed intolerance to NSAIDs therapy);11.Have acceptable current use of NSAIDs at Screening: a)If currently using an NSAID, must be on a stable daily dose for at least 14 days prior to Screening b)If not currently using an NSAID, short-term use is allowed (up to 1 week) during Period 1 and is allowed as needed during Period 2;12.Have no history of untreated latent or active tuberculosis;13.Be judged to be medically stable, other than nr-axSpA, based on medical history, physical examination, and routine laboratory tests;14.Undergo screening for hepatitis B virus (HBV), which at a minimum includes testing for HBV surface antigen (HBsAg), HBV surface antibody (anti-HBs), and HBV core antibody (anti-HBc total), and demonstrate to be eligible based on the results as described in the protocol
1.Has bilateral sacroiliitis Grade 2 or unilateral sacroiliitis Grade 3 or Grade 4 on conventional x-rays (to exclude subjects who meet modified New York criteria for AS);2.If female, is nursing, pregnant, or intending to become pregnant within 6 months after receiving the last administration of trial medication;3. Intends to donate eggs (female subjects) or sperm (male subjects) while receiving trial medication or within 6 months after the last dose of trial medication.;4.Has any clinically significant condition or situation, other than those listed as exclusion criteria that, in the opinion of the investigator, would interfere with the trial evaluations or participation in the trial;5.Has ever received any cytotoxic drugs, including but not limited to chlorambucil, cyclophosphamide, nitrogen mustard, or other alkylating agents;6. Has received any treatment as described in the protocol more recently than the indicated offdrug period prior to Screening;7.Has ever received TNF-a targeted therapy or any other biological agents intended to treat immune-mediated diseases, including but not limited to infliximab, etanercept, adalimumab, certolizumab, golimumab, alefacept, efalizumab, rituximab, natalizumab, secukinumab, ixekizumab, ustekinumab, or vedolizumab;8.Has an allergy/sensitivity to golimumab or its excipients;9.Has any systemic inflammatory condition from Screening up to Baseline with signs and symptoms including, but not limited to: a. psoriatic arthritis, b. active Lyme disease, c. systemic lupus erythematosus, d. infectious arthritis, e. vasculitis, f. parvovirus infection, g. rheumatoid arthritis, h. active uveitis, i. active IBD;10.Has a history of latent or active granulomatous infection, including histoplasmosis, or coccidioidomycosis, prior to Screening;11.Had a nontuberculous mycobacterial infection or opportunistic infection (e.g., cytomegalovirus, Pneumocystis jirovecii [carinii], aspergillus) within 6 months prior to Screening;12.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;13.Had a serious infection (including but not limited to, hepatitis, pneumonia, sepsis, or pyelonephritis), or has been hospitalized for an infection, or has been treated with IV antibiotics for an infection within 2 months prior to Baseline. Less serious infections (eg, acute upper respiratory tract infection, simple urinary tract infection) need not be considered exclusionary at the discretion of the investigator;14.Had a history of, or ongoing, chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection (e.g., bronchiectasis), sinusitis, recurrent urinary tract infection (e.g., recurrent pyelonephritis, chronic nonremitting cystitis), an open, draining, or infected skin wound, or an ulcer;15.Is known to be infected with human immunodeficiency virus (HIV) or seropositive for hepatitis C virus (HCV);16.Has a chest x-ray within 2 months prior to Screening that shows an abnormality suggestive of a current active infection or malignancy;17.Has a history of lymphoproliferative disease, including lymphoma, or signs suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location and/or clinically significant splenomegaly, or monoclonal gammopathy of undetermined significance;18.Has had a malignancy within 5 years before screeni
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy endpoint for this trial is the proportion of subjects<br /><br>without a disease activity *flare* during up to 12 months in Period 2 (in<br /><br>subjects who attained inactive disease status after receiving open-label<br /><br>golimumab in Period 1).<br /><br><br /><br>A *flare* is defined as ASDAS at two consecutive visits that both show either<br /><br>absolute score >=2.1 or post-withdrawal increase (i.e., change from Visit 23) of<br /><br>>=1.1.</p><br>
- Secondary Outcome Measures
Name Time Method <p>During Period 2:<br /><br>- Proportion of subjects with a *flare* in the treatment-withdrawal group or<br /><br>the reducedtreatment group who then show a clinical response after re-treatment<br /><br>with open-label golimumab;<br /><br>- Time to a first *flare*;<br /><br>- Proportion of subjects achieving ASAS20 response;<br /><br>- Proportion of subjects achieving ASAS40 response;<br /><br>- Proportion of subjects achieving BASDAI50 response;<br /><br>- Proportion of subjects achieving ASAS partial remission;<br /><br>- Proportion of subjects achieving inactive disease status: ASDAS <1.3 score.<br /><br><br /><br>for exploratory endopints please refer to protocol chapter 8.4.1.3</p><br>