Treatment of non-radiographic axial spondyloarthritis (nr-axSpA) MedDRA version: 20.0 Level: LLT Classification code 10076297 Term: Non-radiographic axial spondyloarthritis System Organ Class: 100000004859
Conditions
Interventions
Trade Name: SIMPONI
Product Name: golimumab
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: GOLIMUMAB
CAS Number: 476181-74-5
Current Sponsor code: MK-8259
Conce
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 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 screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: In adults with active nr-axSpA who attain inactive disease after receiving open label golimumab during a 10-month run-in (Period 1): To evaluate the effect of treatment withdrawal vs continued treatment with golimumab (either QM or Q2M) on the incidence of a “flare” during up to 12 months of Period 2.;Secondary Objective: In subjects who withdraw from or continue treatment with golimumab during Period 2: 1.To characterize the proportion of subjects with a “flare” in the treatmentwithdrawal group or the reduced-treatment group who then show a clinical response after retreatment with open-label golimumab. 2.To evaluate the time to first “flare” after withdrawal of golimumab vs continuous treatment with golimumab (either QM or Q2M). 3.To evaluate the symptoms and signs of nr-axSpA (e.g., Assessment of SpondyloArthritis international Society [ASAS]20, ASAS40, BASDAI50, ASAS partial remission and ASDAS <1.3) after withdrawal of golimumab vs continuous treatment with golimumab (either QM or Q2M) and after re-treatment with openlabel golimumab if needed for a “flare”. 4.To characterize the safety and tolerability of golimumab treatment.;Primary end point(s): Proportion of subjects without a “flare” during up to 12 months in Period 2.;Timepoint(s) of evaluation of this end point: 12 months of Period 2 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): None;Timepoint(s) of evaluation of this end point: None | — |
Countries
Czech Republic, Germany, Netherlands, Poland, Russian Federation, Spain, Turkey
Contacts
Public ContactGeorge Philip
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Outcome results
None listed