KPL-301 for Subjects With Giant Cell Arteritis

Giant Cell Arteritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03827018
• Other study ID #: KPL-301-C001
• Status: Completed
• Phase: Phase 2
• Start date: September 20, 2018
• Est. completion date: November 25, 2020

Study information

• Verified date: October 2023
• Source: Kiniksa Pharmaceuticals, Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: November 25, 2020
• Est. primary completion date: August 13, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arteritis
• Giant Cell Arteritis
• Polymyalgia Rheumatica

Intervention

Combination Product:
• mavrilimumab
1 mL of 150 mg in a pre-filled syringe
• placebo
1 mL of placebo in a pre-filled syringe

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)

Locations

Country	Name	City	State
Australia	Site 2102	Kogarah
Australia	Site 2105	Nedlands
Australia	Site 2106	Parkville
Australia	Site 2101	Victoria Park
Australia	Site 2104	Woodville South
Belgium	Site 2204	Brussels
Belgium	Site 2202	Leuven
Belgium	Site 2201	Liège
Belgium	Site 2203	Yvoir
Croatia	Site 2303	Zagreb
Estonia	Site 2401	Tallinn
Estonia	Site 2402	Tartu
Germany	Site 2504	Erlangen	Bayern
Germany	Site 2507	Freiburg im Breisgau
Germany	Site 2506	Hamburg
Germany	Site 2503	Hannover
Germany	Site 2508	Jena
Germany	Site 2501	Kirchheim Unter Teck
Germany	Site 2502	Tuebingen	Baden-Württemberg
Ireland	Site 2601	Dublin
Italy	Site 2703	Milano
Italy	Site 2701	Pieve Emanuele
Italy	Site 2702	Reggio Emilia
Italy	Site 2704	Udine
Netherlands	Site 2802	Groningen
Netherlands	Site 2801	Rotterdam
New Zealand	Site 2902	Christchurch
New Zealand	Site 2901	Wellington
Poland	Site 1002	Kraków
Serbia	Site 1101	Belgrade
Serbia	Site 1102	Belgrade
Serbia	Site 1103	Belgrade
Slovenia	Site 1201	Ljubljana
Spain	Site 1303	A Coruña
Spain	Site 1301	Barcelona
Spain	Site 1304	Bilbao
Spain	Site 1302	Santa Cruz De Tenerife
United Kingdom	Site 1604	Edinburgh
United Kingdom	Site 1603	Essex
United Kingdom	Site 1602	London
United Kingdom	Site 1601	Newcastle Upon Tyne
United States	Site 1706	Atlanta	Georgia
United States	Site 1701	Boston	Massachusetts
United States	Site 1707	Lansing	Michigan
United States	Site 1705	New York	New York
United States	Site 1702	Rochester	Minnesota
United States	Site 1704	Saint Clair Shores	Michigan
United States	Site 1703	Sarasota	Florida
United States	Site 1708	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Kiniksa Pharmaceuticals, Ltd.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Croatia,  Estonia,  Germany,  Ireland,  Italy,  Netherlands,  New Zealand,  Poland,  Serbia,  Slovenia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Cumulative Corticosteroid Dose at Week 26		Week 26
Secondary	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
Secondary	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
Secondary	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
Secondary	Cumulative Corticosteroid Dose at the End of the Washout Safety Follow-up Period		Final Safety Follow-up visit (Week 38)