Tocilizumab Plus a Short Prednisone Taper for GCA

NCT03726749 | Completed Phase 4 Results FDA Drug

• 1 other identifier: ML40859
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label pilot study of tocilizumab (TCZ) 162 mg weekly administered subcutaneously for 52 weeks in combination with 8 weeks of oral prednisone.

Conditions

Giant Cell Arteritis

Keywords

GCA; Tocilizumab; Prednisone

Outcome Measures

Primary Outcomes (1)

• Sustained Remission

  Number and percentage of patients in sustained remission by week 52. Sustained remission was defined as the absence of disease flare between baseline and week 52. Flare was defined as the re-appearance of clinical manifestations of GCA with or without elevation of the inflammatory makers erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP)

  52 weeks

Secondary Outcomes (4)

• Disease Flares

  52 Weeks

• Cumulative Prednisone Dose

  52 Weeks

• Adverse Events

  52 weeks

• Serious Adverse Events

  52 weeks

Study Arms (1)

Tocilizumab and prednisone

EXPERIMENTAL

1. TCZ 162 mg administered by subcutaneous injection weekly for 52 weeks. 2. Prednisone taper over 8 weeks with a starting dose between 20 and 60 mg.

Drug: Tocilizumab; Drug: Prednisone

Interventions

Tocilizumab DRUG

Tocilizumab is an interleukin-6 (IL-6) receptor inhibitor

Also known as: ACTEMRA®

Tocilizumab and prednisone

Prednisone DRUG

Prednisone is an anti-inflammatory medication

Also known as: Glucocorticoids

Tocilizumab and prednisone

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability and willingness to provide written informed consent and to comply with the study protocol
• Diagnosis of GCA classified per the following criteria:
• Age 50 years or older
• AND at least one of the following:
• Unequivocal cranial symptoms of GCA (new-onset localized headache, scalp tenderness, temporal artery tenderness or decreased pulsation, ischemia-related vision loss, or otherwise unexplained mouth or jaw pain upon mastication)
• Symptoms of polymyalgia rheumatica (PMR), defined as shoulder and / or hip girdle pain associated with inflammatory morning stiffness
• AND at least one of the following:
• Cranial artery biopsy revealing features of GCA (e.g., mononuclear cell infiltration or granulomatous inflammation).
• Evidence of large-vessel vasculitis by angiography or cross-sectional imaging study such as Image result for magnetic resonance angiogram (MRA), Computed tomography angiography (CTA) , or Image result for positron emission tomography (PET) and computed tomography (CT) (PET-CT)
• Ultrasound demonstration of features of GCA in a cranial artery.
• New-onset or relapsing/refractory active disease defined as follows:
• New onset: diagnosis of GCA within 6 weeks of baseline visit
• Relapsing/refractory: diagnosis of GCA \> 6 weeks before baseline visit
• AND
• Active GCA within 6 weeks of baseline visit defined as the presence of clinical signs and symptoms \[cranial or PMR\] and erythrocyte sedimentation rate (ESR) ≥ 30 mm/hour or C-reactive protein (CRP) ≥ 10 mg/L)

You may not qualify if:

• Major surgery within 8 weeks prior to screening or planned major surgery within 12 months after randomization
• Transplanted organs (except corneal transplant performed more than 3 months prior to screening)
• Major ischemic event, unrelated to GCA, within 12 weeks of screening
• Treatment with any investigational agent within 12 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening
• Previous treatment with cell-depleting therapies, including investigational agents, including but not limited to Campath (alemtuzumab), anti-CD4 (cluster of differentiation 4), anti-CD5, anti-CD3, anti-CD19, and anti-CD20
• Previous treatment with alkylating agents, such as chlorambucil, or with total lymphoid irradiation
• Immunization with a live/attenuated vaccine within ≤ 4 weeks prior to baseline
• Treatment with cyclosporine A, azathioprine, cyclophosphamide or Mycophenolate mofetil (MMF) within 4 weeks of baseline. Patients on methotrexate at screening will require discontinuation of this agent prior to baseline visit.
• Treatment with etanercept within 2 weeks; infliximab, certolizumab, golimumab, abatacept, or adalimumab within 8 weeks; or anakinra within 1 week of baseline
• Patients requiring systemic glucocorticoid therapy for conditions other than GCA, which, in the opinion of the investigator, would interfere with adherence to the fixed glucocorticoid taper regimen and/or to assessment of efficacy in response to TCZ
• Inability, in the opinion of the investigator, to withdraw GC treatment through protocol-defined taper regimen due to suspected or established adrenal insufficiency
• Patients treated with TCZ before will be permitted to participate in the trial if they demonstrated treatment efficacy and they did not discontinue TCZ because of an adverse effect.
• History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies or to prednisone
• Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), psychiatric, osteoporosis/osteomalacia, glaucoma, corneal ulcers/injuries, or gastrointestinal (GI) disease
• Current liver disease, as determined by the investigator

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Roche-Genentech: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Unizony S, Matza MA, Jarvie A, O'Dea D, Fernandes AD, Stone JH. Treatment for giant cell arteritis with 8 weeks of prednisone in combination with tocilizumab: a single-arm, open-label, proof-of-concept study. Lancet Rheumatol. 2023 Dec;5(12):e736-e742. doi: 10.1016/S2665-9913(23)00265-5. Epub 2023 Nov 2.

  PMID: 38251564 DERIVED

MeSH Terms

Conditions

Giant Cell Arteritis

Interventions

tocilizumab; Prednisone; Glucocorticoids

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Dr Sebastian Unizony
• Organization: MGH

sunizony@mgh.harvard.edu

617-726-7938

Study Officials

• Ana D Fernandes, MA

  Massachusetts General Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine, Harvard Medical School

Study Record Dates

• First Submitted: October 30, 2018
• First Posted: October 31, 2018
• Study Start: November 28, 2018
• Primary Completion: December 15, 2021
• Study Completion: December 29, 2021
• Last Updated: December 2, 2022
• Results First Posted: December 2, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)