Primary Efficacy Objective:• To evaluate the efficacy of tocilizumab (TCZ) compared to placebo, in combination with a26-week prednisone taper regimen, in patients with giant cell arteritis (GCA), as measured by the proportion of patients in…
ID
Source
Brief title
Condition
- Immune disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy Outcome Measures:
1) Assessment of GCA disease activity based on the presence or absence of signs
and symptoms
2) Assessment of acute phase reactants ESR and CRP
3) Assessment of prednisone dose and duration
Secondary outcome
Safety Outcome Measures:
1) Incidence, nature, and severity of adverse events
2) Laboratory abnormalities including but not limited to neutropenia, liver
function test abnormalities, thrombocytopenia, and lipid level abnormalities
3) Incidence of anti-TCZ antibodies
Pharmacodynamic Outcome Measures:
1) IL-6
2) sIL-6R
3) ESR and CRP
Pharmacokinetic Outcome Measures:
1) TCZ concentration
2) Derived PK parameters as follows:
- AUC*, Cmax, and Cmin at steady state for 162 mg qw and 162 mg q2w for
patients in the PK substudy
- Predose TCZ concentration (Ctrough) for all patients
Patient-Reported Outcome Measures:
1) PGA (VAS)
2) SF-36
3) EQ-5D
4) FACIT-Fatigue
Background summary
Corticosteroids (CS) are the mainstay of treatment for GCA. Although CS are
highly effective at inducing remission of systemic inflammation and preventing
acute damage (e.g., blindness), this comes with a high toxicity burden, with
86% of patients suffering CS-related adverse clinical events at 10-year
follow-up.
In addition, CS are not as effective at maintaining remission, with many
patients (up to 50%) experiencing relapse or flare-up of symptoms during
reduction or discontinuation of CS.
An effective and safe CS-sparing therapy for patients with new-onset or
refractory GCA remains elusive and constitutes a high unmet medical need.
Study objective
Primary Efficacy Objective:
• To evaluate the efficacy of tocilizumab (TCZ) compared to placebo, in
combination with a
26-week prednisone taper regimen, in patients with giant cell arteritis (GCA),
as measured by the proportion of patients in sustained remission at Week 52
following induction and adherence to the protocol-defined prednisone taper
regimen
Key Secondary Objective
• To evaluate the efficacy of TCZ in combination with a 26-week prednisone
taper regimen versus placebo in combination with a 52-week prednisone taper
regimen, in patients with GCA, as measured by the proportion of patients in
sustained remission at Week 52 following induction and adherence to the
protocol-defined prednisone taper regimen
Other secondary objectives:
1) To assess the efficacy of TCZ in combination with a 26-week prednisone taper
regimen versus both placebo groups, in patients with GCA
2) To assess the effect on patient*s quality of life of TCZ in combination with
a 26-week prednisone taper regimen versus placebo based on the patient-reported
outcome (PRO)
3) To assess the pharmacokinetics (PK) and pharmacodynamics (PD) of TCZ in
combination with a 26-week prednisone taper regimen in patients with GCA
Study design
This is a Phase III, multicenter, randomized, placebo-controlled, double-blind,
parallel-group trial in patients with GCA. The primary endpoint, the proportion
of patients in sustained remission, will be evaluated at 52 weeks. There will
be a 52-week blinded period (Part 1) followed by a 104-week open-label period
(Part 2), with a total duration of the study of 156 weeks.
Intervention
A planned total of approximately 250 patients will be enrolled and assigned to
one of four arms. Patients will be randomized in a 2:1:1:1 ratio to receive the
following treatments:
• Group A: 162 mg of subcutaneous (SC) TCZ every week (qw) + 26-week prednisone
taper regimen (n = 100)
• Group B: 162 mg of SC TCZ every other week (q2w) + 26-week prednisone taper
regimen (n =50)
• Group C: SC placebo + 26-week prednisone taper regimen (n = 50)
• Group D: SC placebo + 52-week prednisone taper regimen (n = 50)
Study burden and risks
1) Assessments during screening: tuberculosis screening, physical examination,
vital signs, weight, height, ECG, thorax X-ray, blood sample, urine sample, GCA
assessment.
2) Assessments during part 1 (52 wks, double blind, max. 18 planned visits):
physical exam 1x, vital signs all visits, weight 3x, blood sample all visits,
questionnaires 6x, urine sample 1x, GCA assessment all visits.
3) Assessments during part 2 (2nd and 3rd year, open label extension/long term
follow-up, max 13 planned visits): physical exam 1x, vital signs 6x, weight 2x,
blood sample all visits, questionnaires all visits, GCA assessment all visits.
Follow-Up (2 visits): blood sample 1x
In case of early withdrawal the assessments under 3) will be repeated once.
The most common side effects of TCZ are common colds, sinusitis, and throat
infection. Other common side effects are abdominal pain, mouth ulceration,
rash, stomach upset, an increase in blood pressure, weight increase, headache,
dizziness, cough, shortness of breath, conjunctivitis, and swelling of the
legs, ankles and/or feet.
In addition, the following problems may be experienced: diverticulitis, serious
infection cancer (There have been very few reports of cancer in patients
treated with TCZ. However, a potential risk for development of cancer cannot
be excluded), increases in liver enzymes, blood cholesterol increases,
decreases in neutrophil/white blood cell counts, decreases in platelet counts,
yypersensitivity reactions and anaphylaxis, and demyelinating disorders.
Potential side effects of Prednisone are nausea, vomiting, loss of appetite,
heartburn, trouble sleeping, increased sweating, and acne. The following side
effects are less likely to occur: muscle pain/cramps, irregular heartbeat,
weakness, swelling of the hands/ankles/feet, unusual weight gain, signs of
infection, vision problems (such as blurred vision), vomit that looks like
coffee grounds, black bloody stools, severe stomach/abdominal pain, mental/mood
changes (such as depression, mood swings, agitation), slow wound healing,
thinning skin, bone pain, menstrual period changes, puffy face, seizures, and
easy bruising/bleeding. Also the blood sugar level may rise, which can
worsen/cause diabetes.
Possible risks of blood drawing and tuberculosis skin test: pain, bruising,
infection, dizziness, upset stomach, or fainting.
Possible risks of X-Rays: a slight chance of excessive exposure of radiation
with chest x-rays (about the same as the average person receives from
background radiation in 10 days).
Possible risks of ECG: cold sticky pads, redness, itching, and potentially
irritation from shaving.
The reproductive risk is unknown, so contraception should be used.
Grenzacherstrasse 124
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Grenzacherstrasse 124
Basel 4070
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Listed location countries
Age
Inclusion criteria
- Able and willing to provide written informed consent and to comply with the study protocol
- Diagnosis of GCA
- New-onset or refractory active disease
Exclusion criteria
- 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
- Previous treatment with cell-depleting therapies, including investigational agents, including but not limited to Campath (alemtuzumab), anti-CD4, anti-CD5, anti-CD3, anti-CD19, and anti-CD20
- Treatment with IV gamma globulin or plasmapheresis within 6 months of baseline
- Previous treatment with alkylating agents, such as chlorambucil, or with total lymphoid irradiation
- Previous treatment with TCZ
- Immunization with a live/attenuated vaccine within <= 4 weeks prior to baseline
- Treatment with hydroxychloroquine, cyclosporine A, azathioprine, or MMF within 4 weeks of
Baseline
- Treatment with etanercept within 2 weeks; infliximab, certolizumab, golimumab, abatacept, or adalimumab within 8 weeks; or anakinra within 1 week of baseline
- Previous treatment with tofacitinib
- Treatment with cyclophosphamide within 6 months of baseline
- Patients requiring systemic CS for other conditions other than GCA, which, in the opinion of the investigator, would interfere with adherence to the fixed CS taper regimen and/or to assessment of efficacy in response to the test article
- Chronic use of systemic CS for > 4 years or inability, in the opinion of the investigator, to withdraw CS treatment through protocol-defined taper regimen due to suspected or established adrenal insufficiency
- Receipt of > 100 mg daily intravenous methylprednisolone within 6 weeks of baseline
- Active TB requiring treatment within the previous 3 years
- Females of childbearing potential and females who are breastfeeding
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-006022-25-NL |
| ClinicalTrials.gov | NCT01791153 |
| CCMO | NL42377.042.13 |