A Study to Evaluate the Efficacy of Tocilizumab as a Remission-Induction and Glucocorticoid-Sparing Regimen in Subjects With New-Onset Polymyalgia Rheumatica (PMR- SPARE)

NCT03263715 | Completed Phase 3

• 2 other identifiers: PMR-SPARE2016-004990-42
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to assess the efficacy of a tocilizumab-based regimen compared with placebo on top of rapidly tapered glucocorticoid treatment in a double- blind, controlled fashion, focussing on glucocorticoid-free remission of disease.

Conditions

Polymyalgia Rheumatica

Keywords

Polymyalgia Rheumatica; Tocilizumab; Glucocorticoid; Glucocorticoid-Sparing

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects in GC free remission at week 16

  Proportion of subjects in GC free remission at week 16

  Week 16

Secondary Outcomes (13)

• Cumulative prednisone doses at weeks 12, 16 and 24

  Week 12, 16, 24

• Number of flares per patient at weeks 12, 16 and 24

  Week 12, 16, 24

• Time to first and second flare

  24 Weeks

• Patient reported outcomes including SF-36

  24 Weeks

• Patient reported outcomes including FACIT-Fatigue

  24 Weeks

Study Arms (2)

Tocilizumab

EXPERIMENTAL

Tocilizumab-based regimen (Tocilizumab Prefilled Syringe \[Actemra\] 162 mg s.c. administered weekly) on top of rapidly tapered Glucocorticoid \[Glucocorticoids\]

Drug: Tocilizumab Prefilled Syringe [Actemra]; Drug: Glucocorticoids

Placebo

PLACEBO COMPARATOR

Placebo \[Placebos\] and rapidly tapered Glucocorticoid \[Glucocorticoids\] treatment

Drug: Placebos; Drug: Glucocorticoids

Interventions

Tocilizumab Prefilled Syringe [Actemra] DRUG

Weekly administration of Tocilizumab 162 mg subcutaneous from Baseline to Week 16.

Also known as: Actemra

Tocilizumab

Placebos DRUG

Weekly administration of Placebo subcutaneous from Baseline to Week 16.

Placebo

Glucocorticoids DRUG

Rapidly tapered Glucocorticoid treatment. 20 mg/day of prednisone at randomization and a pre-specified taper regimen will be followed over 11 weeks: Week 0: 20 mg Week 1: 17,5 mg Week 2: 15 mg Week 3: 12,5 mg Week 4: 10 mg Week 5: 9 mg Week 6: 7 mg Week 7: 5 mg Week 8: 4 mg Week 9: 2 mg Week 10: 1 mg Week 11: 0 mg

Placebo; Tocilizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of PMR as confirmed by the investigator at screening and at baseline, fulfilment (also in retrospect) of the provisional 2012 ACR- EULAR classification criteria
• Diagnosis of PMR established at, or up to 2 weeks before the screening visit
• GC naïve or on GC treatment for a maximum of 2 weeks at screening with an initial dose between 12.5 and 25mg/day prednisone
• Willing and able to receive oral prednisone 20mg/day at randomization and to follow a pre-specified tapering regimen
• Willing to receive treatment for prevention of GC-induced bone loss
• No evidence of active infection with Mycobacterium tuberculosis (screening performed according to national guidelines) and willing to take TB prophylaxis in case of evidence of latent TB
• Willing and being able to understand and follow the study procedures
• Male and female subjects agreeing to conduct efficient contraception (unless they have no childbearing potential)
• Written informed consent.
• Female and Male subjects from 18 years old and higher

You may not qualify if:

• Evidence of GCA (cranial or large vessel) as indicated by unequivocal clinical symptoms (except PMR), imaging and/or biopsy results. Routine screening of eligible PMR patients for GCA with imaging methods or temporal artery biopsy is not recommended
• GC treatment of PMR \>2 weeks
• Conditions other than PMR requiring continuous or intermittent treatment with oral or parenteral GCs or parenteral administration of GCs, unless the last exposure to GCs was \>1 months before screening
• Other inflammatory rheumatic diseases (e.g. rheumatoid arthritis)
• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization
• Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening
• Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples include: CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20
• Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline
• Immunization with a live/attenuated vaccine within 4 weeks prior to baseline
• Previous treatment with Tocilizumab (an exception to this criterion may be granted for single dose exposure upon application to the sponsor on a case-by-case basis)
• Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation
• History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
• Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated diverticulitis, ulcerative colitis, or Crohn ́s disease)
• Diagnosis of liver disease or elevated hepatic enzymes, as defined by ALT, AST, or both \> 1.5 x the upper limit of age-determined normal (ULN) or total bilirubin \> ULN
• Serum creatinine \> 1.6 mg/dL (141 μmol/L) in female patients and \> 1.9 mg/dL (168 μmol/L) in male patients. Patients with serum creatinine values exceeding limits may be eligible for the study, if their estimated glomerular filtration rates (GFR) are \> 30

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (3)

Medizinische Universität Graz, Klinische Abteilung für Rheumatologie und Immunologie

Graz, 8036, Austria

Location

Allgemeines Krankenhaus der Stadt Wien

Vienna, 1090, Austria

Location

Krankenhaus Hietzing, 2. Medizinische Abteilung

Vienna, 1130, Austria

Location

Related Publications (1)

• Bonelli M, Radner H, Kerschbaumer A, Mrak D, Durechova M, Stieger J, Husic R, Mandl P, Smolen JS, Dejaco C, Aletaha D. Tocilizumab in patients with new onset polymyalgia rheumatica (PMR-SPARE): a phase 2/3 randomised controlled trial. Ann Rheum Dis. 2022 Jun;81(6):838-844. doi: 10.1136/annrheumdis-2021-221126. Epub 2022 Feb 24.

  PMID: 35210264 DERIVED

MeSH Terms

Conditions

Polymyalgia Rheumatica

Interventions

tocilizumab; Glucocorticoids

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 17, 2017
• First Posted: August 28, 2017
• Study Start: November 24, 2017
• Primary Completion: June 2, 2020
• Study Completion: June 2, 2020
• Last Updated: January 22, 2021

Record last verified: 2021-01

Locations

AU (3)