KPL-301 for Subjects With Giant Cell Arteritis

A Phase 2, Randomized, Double-blind Placebo-controlled Study to Test the Efficacy and Safety of KPL-301 in Giant Cell Arteritis

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).

Study Overview

• Status: Completed
• Conditions: Giant Cell Arteritis
• Intervention / Treatment: Combination product: mavrilimumab; Drug: prednisone; Combination product: placebo

Detailed Description

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
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Kogarah, Australia, 2217
    • Site 2102
  • Nedlands, Australia, 6009
    • Site 2105
  • Parkville, Australia, 3050
    • Site 2106
  • Victoria Park, Australia, 6100
    • Site 2101
  • Woodville South, Australia, 5011
    • Site 2104
• Belgium
  • Brussels, Belgium, 1070
    • Site 2204
  • Leuven, Belgium, 3000
    • Site 2202
  • Liège, Belgium, 4000
    • Site 2201
  • Yvoir, Belgium, 5530
    • Site 2203
• Croatia
  • Zagreb, Croatia, 10 000
    • Site 2303
• Estonia
  • Tallinn, Estonia, 11312
    • Site 2401
  • Tartu, Estonia, 50708
    • Site 2402
• Germany
  • Freiburg im Breisgau, Germany, 79106
    • Site 2507
  • Hamburg, Germany, 22763
    • Site 2506
  • Hannover, Germany, 30625
    • Site 2503
  • Jena, Germany, 07747
    • Site 2508
  • Kirchheim Unter Teck, Germany, 73230
    • Site 2501
  • Baden-Württemberg
    • Tuebingen, Baden-Württemberg, Germany, 72076
      • Site 2502
  • Bayern
    • Erlangen, Bayern, Germany, 91054
      • Site 2504
• Ireland
  • Dublin, Ireland, D04 T6F4
    • Site 2601
• Italy
  • Milano, Italy, 20132
    • Site 2703
  • Pieve Emanuele, Italy, 20090
    • Site 2701
  • Reggio Emilia, Italy, 42100
    • Site 2702
  • Udine, Italy, 33100
    • Site 2704
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Site 2802
  • Rotterdam, Netherlands, 3015 GD
    • Site 2801
• New Zealand
  • Christchurch, New Zealand, 8083
    • Site 2902
  • Wellington, New Zealand, 6021
    • Site 2901
• Poland
  • Kraków, Poland, 31-121
    • Site 1002
• Serbia
  • Belgrade, Serbia, 11000
    • Site 1103
  • Belgrade, Serbia, 11000
    • Site 1101
  • Belgrade, Serbia, 11000
    • Site 1102
• Slovenia
  • Ljubljana, Slovenia, 1000
    • Site 1201
• Spain
  • A Coruña, Spain, 15006
    • Site 1303
  • Barcelona, Spain, 08036
    • Site 1301
  • Bilbao, Spain, 48013
    • Site 1304
  • Santa Cruz De Tenerife, Spain, 38320
    • Site 1302
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Site 1604
  • Essex, United Kingdom, SS0 0RY
    • Site 1603
  • London, United Kingdom, E11 1NR
    • Site 1602
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Site 1601
• United States
  • Florida
    • Sarasota, Florida, United States, 34239
      • Site 1703
    • Tampa, Florida, United States, 33612
      • Site 1708
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Site 1706
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Site 1701
  • Michigan
    • Lansing, Michigan, United States, 48910
      • Site 1707
    • Saint Clair Shores, Michigan, United States, 48081
      • Site 1704
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Site 1702
  • New York
    • New York, New York, United States, 10021
      • Site 1705

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Selected Inclusion Criteria:

1. Subjects with new-onset or relapsing/refractory GCA.
2. Westergren erythrocyte sedimentation rate > 30 mm/hour or c-reactive protein ≥ 1 mg/ dL.
3. Remission of GCA at or before Day 0.
4. Female subjects must be postmenopausal or permanently sterile following documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or tubal ligation or having a male partner with vasectomy as affirmed by the subject, or nonpregnant, nonlactating, and if sexually active having agreed to use a highly effective method of contraception.
5. Male subjects must have documented vasectomy or if sexually active must agree to use a highly effective method of contraception with their partners of childbearing potential.

Selected Exclusion Criteria:

1. Transplanted organs (except corneal transplant performed more than 3 months prior to randomization).
2. Concurrent enrollment in another interventional clinical study.
3. Treatment with non-biologic investigational drug therapy within 4 weeks or 5 half-lives of the study agent, whichever was longer, prior to screening.
4. Cell-depleting biological therapies within 12 months prior to Day 0, or noncell-depleting biological therapies within 8 weeks (or 5 half-lives, whichever is longer) prior to screening.
5. Treatment with alkylating agents within 12 weeks prior to screening.
6. Intramuscular, Intra-articular or IV corticosteroids within 4 weeks prior to screening.
7. Receipt of live (attenuated) vaccine within the 4 weeks before Day 0.
8. Treatment with hydroxychloroquine, cyclosporine A, azathioprine, cyclophosphamide, or mycophenolate mofetil (MMF) within 4 weeks of screening.
9. Female subjects who are pregnant, intending to become pregnant, or are breastfeeding.
10. Known history of allergy or reaction to any component of the mavrilimumab or placebo formulation or to any other biologic therapy or prednisone or any of its excipients.
11. Positive (or 2 indeterminate) QuantiFERON test results.
12. Clinically significant active infection or infection requiring hospitalization or IV antibiotics within 12 weeks before screening or opportunistic infection within 6 months before screening.
13. Chronic active hepatitis B infection.
14. Subjects at a high risk of infection, a history of an infected joint prosthesis still in situ, leg ulcers, indwelling urinary catheter, or persistent or recurrent chest infections.
15. History of cancer within the last 10 years, except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured.
16. Evidence of clinically-uncontrolled respiratory disease.
17. History of chronic respiratory tract infections.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: mavrilimumab; Subjects randomized to mavrilimumab will receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Combination product: mavrilimumab; 1 mL of 150 mg in a pre-filled syringe; Other Names: KPL-301; Drug: prednisone; 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)
Placebo Comparator: placebo; Subjects randomized to placebo will receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Drug: prednisone; 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); Combination product: placebo; 1 mL of placebo in a pre-filled syringe

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	Week 26
Cumulative Corticosteroid Dose at Week 26		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.	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.	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.	Week 26
Cumulative Corticosteroid Dose at the End of the Washout Safety Follow-up Period		Final Safety Follow-up visit (Week 38)

Collaborators and Investigators

• Sponsor: Kiniksa Pharmaceuticals, Ltd.
• Investigators: Study Director: John Paolini, M.D., Kiniksa Pharmaceuticals, Ltd.

Publications and helpful links

General Publications

• Cid MC, Unizony SH, Blockmans D, Brouwer E, Dagna L, Dasgupta B, Hellmich B, Molloy E, Salvarani C, Trapnell BC, Warrington KJ, Wicks I, Samant M, Zhou T, Pupim L, Paolini JF; KPL-301-C001 Investigators. Efficacy and safety of mavrilimumab in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2022 May;81(5):653-661. doi: 10.1136/annrheumdis-2021-221865. Epub 2022 Mar 9.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2018
• Primary Completion (Actual): August 13, 2020
• Study Completion (Actual): November 25, 2020

Study Registration Dates

• First Submitted: January 25, 2019
• First Submitted That Met QC Criteria: January 31, 2019
• First Posted (Actual): February 1, 2019

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: GCA; temporal arteritis; Horton's disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Muscular Diseases; Vasculitis; Skin Diseases, Vascular; Vasculitis, Central Nervous System; Polymyalgia Rheumatica; Giant Cell Arteritis; Arteritis; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone; Mavrilimumab
• Other Study ID Numbers: KPL-301-C001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes