The primary objective of the study is to evaluate the efficacy of mavrilimumab (KPL-301) versus placebo, co-administered with a 26-week corticosteroid taper, for maintaining sustained remission for 26 weeks in subjects with new onset or relapsing/refractory giant cell arteritis (GCA).
This Phase 2 randomized, double-blind, placebo-controlled proof of concept study will evaluate the efficacy and safety of mavrilimumab co-administered with a 26-week corticosteroid taper in subjects with GCA. The study will consist of a screening period (up to 6 weeks), a 26-week double-blind placebo-controlled period during which subjects will receive blinded mavrilimumab or placebo co-administered with a 26-week corticosteroid taper, and a 12-week washout safety follow-up period during which subjects will discontinue and wash off blinded mavrilimumab or placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
70
1 mL of 150 mg in a pre-filled syringe
1 mL of placebo in a pre-filled syringe
Prednisone tablets for oral administration containing either 1 mg, 2.5 mg, 5 mg, 10 mg, 20 mg or 50 mg of prednisone United States Pharmacopeia (USP)
Time to Flare by Week 26
Time to flare by Week 26 was defined as time from randomization to the date of first flare occurring within the 26-week period, as assessed by independent adjudication. Kaplan-Meier method used to estimate the survival functions for each treatment arm. Flare/relapse was defined as a C-reactive protein (CRP) of 1 mg/dL or greater and/or erythrocyte sedimentation rate (ESR) of 30 mm/h or greater AND at least one of the following signs or symptoms attributed to GCA: Cranial symptoms (new-onset localized headache; scalp or temporal artery tenderness; ischemic-related vision loss; unexplained mouth or jaw pain upon mastication; transient ischemic attack or stroke related to GCA); Extracranial symptoms (claudication of the extremities; symptoms of polymyalgia rheumatica); New or worsening angiographic abnormalities detected via MRI, CT/CTA, or PET-CT of the aorta or other great vessels or via ultrasound of the temporal arteries.
Time frame: Week 26
Sustained Remission Rate at Week 26
The sustained remission rate at Week 26 is defined as the percentage of participants with sustained remission, as assessed by independent adjudication, at Week 26, derived from the time to flare curve. Kaplan-Meier Survival Estimates with standard error and 95% CI for each arm. Participants who completed the treatment period without a flare by Week 26 were considered to have sustained remission.
Time frame: Week 26
Time to Elevated Erythrocyte Sedimentation Rate (ESR) by Week 26
Elevated ESR is defined as first occurrence of ESR value ≥ 30 mm/hr. Participants with elevated ESR within 3 days of first dose are excluded from the analysis. Kaplan-Meier method used to estimate the survival functions for each treatment arm.
Time frame: Week 26
Time to Elevated C-Reactive Protein (CRP) by Week 26
Elevated CRP is defined as first occurrence of CRP value ≥ 1.0 mg/dL. Participants with elevated CRP within 3 days of first dose are excluded from the analysis. Kaplan-Meier method used to estimate the survival functions for each treatment arm.
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Site 1703
Sarasota, Florida, United States
Site 1708
Tampa, Florida, United States
Site 1706
Atlanta, Georgia, United States
Site 1701
Boston, Massachusetts, United States
Site 1707
Lansing, Michigan, United States
Site 1704
Saint Clair Shores, Michigan, United States
Site 1702
Rochester, Minnesota, United States
Site 1705
New York, New York, United States
Site 2102
Kogarah, Australia
Site 2105
Nedlands, Australia
...and 39 more locations
Time frame: Week 26
Time to Signs/Symptoms of Giant Cell Arteritis (GCA) or New or Worsening Vasculitis on Imaging by Week 26
Kaplan-Meier method used to estimate the survival functions for each treatment arm.
Time frame: Week 26
Cumulative Corticosteroid Dose at Week 26
Time frame: Week 26
Percentage of Participants Who Completed the 26-Week Corticosteroid Taper and Who Had a Normal ESR
Participants were considered to have completed the corticosteroid taper if by week 26 receiving 1 mg/day for those who start with 60 mg/day, or 0 mg/day for those who start with doses \< 60 mg/day. 95% CI calculated using Clopper-Pearson confidence intervals.
Time frame: Week 26
Percentage of Participants Who Completed the 26-Week Corticosteroid Taper and Who Had a Normal CRP Level
Participants were considered to have completed the corticosteroid taper if by week 26 receiving 1 mg/day for those who start with 60 mg/day, or 0 mg/day for those who start with doses \< 60 mg/day. 95% CI calculated using Clopper-Pearson confidence intervals.
Time frame: Week 26
Percentage of Participants Who Completed the 26-week Corticosteroid Taper and Who Had No Signs or Symptoms of GCA Nor New or Worsening Vasculitis by Imaging by Week 26
Participants were considered to have completed the corticosteroid taper if by week 26 receiving 1 mg/day for those who start with 60 mg/day, or 0 mg/day for those who start with doses \< 60 mg/day. 95% CI calculated using Clopper-Pearson confidence intervals.
Time frame: Week 26
Cumulative Corticosteroid Dose at the End of the Washout Safety Follow-up Period
Time frame: Final Safety Follow-up visit (Week 38)