Clinical trial NCT03827018: KPL-301 for Subjects With Giant Cell Arteritis
Official title: A Phase 2, Randomized, Double-blind Placebo-controlled Study to Test the Efficacy and Safety of KPL-301 in Giant Cell Arteritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Giant Cell Arteritis
Keywords: GCA
temporal arteritis
Horton's disease
Lead sponsor: Kiniksa Pharmaceuticals International, plc
Sponsor class: INDUSTRY
First posted: 2019-02-01
Enrollment: 70
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Upon successful completion of the screening procedures, diagnosis criteria will be entered into an interactive web response system, and eligible subjects will be stratified for randomized study treatment into two cohorts according to whether subjects have new-onset or relapsing/refractory disease.
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to Flare by Week 26
timeFrame: Week 26
Secondary outcomes:
measure: Sustained Remission Rate at Week 26
timeFrame: Week 26
measure: Time to Elevated Erythrocyte Sedimentation Rate (ESR) by Week 26
timeFrame: Week 26
measure: Time to Elevated C-Reactive Protein (CRP) by Week 26
timeFrame: Week 26
measure: Time to Signs/Symptoms of Giant Cell Arteritis (GCA) or New or Worsening Vasculitis on Imaging by Week 26
timeFrame: Week 26
measure: Cumulative Corticosteroid Dose at Week 26
timeFrame: Week 26
measure: Percentage of Participants Who Completed the 26-Week Corticosteroid Taper and Who Had a Normal ESR
timeFrame: Week 26
measure: Percentage of Participants Who Completed the 26-Week Corticosteroid Taper and Who Had a Normal CRP Level
timeFrame: Week 26
measure: 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
timeFrame: Week 26
measure: Cumulative Corticosteroid Dose at the End of the Washout Safety Follow-up Period
timeFrame: Final Safety Follow-up visit (Week 38)
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Site 1703
state: Florida
city: Tampa
country: United States
facility: Site 1708
state: Florida
city: Atlanta
country: United States
facility: Site 1706
state: Georgia
city: Boston
country: United States
facility: Site 1701
state: Massachusetts
city: Lansing
country: United States
facility: Site 1707
state: Michigan
city: Saint Clair Shores
country: United States
facility: Site 1704
state: Michigan
city: Rochester
country: United States
facility: Site 1702
state: Minnesota
city: New York
country: United States
facility: Site 1705
state: New York
city: Kogarah
country: Australia
facility: Site 2102
city: Nedlands
country: Australia
facility: Site 2105
city: Parkville
country: Australia
facility: Site 2106
city: Victoria Park
country: Australia
facility: Site 2101
city: Woodville South
country: Australia
facility: Site 2104
city: Brussels
country: Belgium
facility: Site 2204
city: Leuven
country: Belgium
facility: Site 2202
city: Liège
country: Belgium
facility: Site 2201
city: Yvoir
country: Belgium
facility: Site 2203
city: Zagreb
country: Croatia
facility: Site 2303
city: Tallinn
country: Estonia
facility: Site 2401
city: Tartu
country: Estonia
facility: Site 2402
city: Tuebingen
country: Germany
facility: Site 2502
state: Baden-Württemberg
city: Erlangen
country: Germany
facility: Site 2504
state: Bayern
city: Freiburg im Breisgau
country: Germany
facility: Site 2507
city: Hamburg
country: Germany
facility: Site 2506
city: Hannover
country: Germany
facility: Site 2503
city: Jena
country: Germany
facility: Site 2508
city: Kirchheim Unter Teck
country: Germany
facility: Site 2501
city: Dublin
country: Ireland
facility: Site 2601
city: Milano
country: Italy
facility: Site 2703
city: Pieve Emanuele
country: Italy
facility: Site 2701
city: Reggio Emilia
country: Italy
facility: Site 2702
city: Udine
country: Italy
facility: Site 2704
city: Groningen
country: Netherlands
facility: Site 2802
city: Rotterdam
country: Netherlands
facility: Site 2801
city: Christchurch
country: New Zealand
facility: Site 2902
city: Wellington
country: New Zealand
facility: Site 2901
city: Kraków
country: Poland
facility: Site 1002
city: Belgrade
country: Serbia
facility: Site 1101
city: Belgrade
country: Serbia
facility: Site 1102
city: Belgrade
country: Serbia
facility: Site 1103
city: Ljubljana
country: Slovenia
facility: Site 1201
city: A Coruña
country: Spain
facility: Site 1303
city: Barcelona
country: Spain
facility: Site 1301
city: Bilbao
country: Spain
facility: Site 1304
city: Santa Cruz De Tenerife
country: Spain
facility: Site 1302
city: Edinburgh
country: United Kingdom
facility: Site 1604
city: Essex
country: United Kingdom
facility: Site 1603
city: London
country: United Kingdom
facility: Site 1602
city: Newcastle Upon Tyne
country: United Kingdom
facility: Site 1601
Study officials:
affiliation: Kiniksa Pharmaceuticals, Ltd.
name: John Paolini, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.