KPL-301 for Subjects With Giant Cell Arteritis

Sponsor

Kiniksa Pharmaceuticals, Ltd. (Industry)

Overall Status

Completed

CT.gov ID

NCT03827018

Collaborator

(none)

Enrollment

Locations

Arms

26.2

Actual Duration (Months)

1.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Giant Cell Arteritis	Combination Product: mavrilimumab Combination Product: placebo Drug: prednisone	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 20, 2018

Actual Primary Completion Date :

Aug 13, 2020

Actual Study Completion Date :

Nov 25, 2020

Arms and Interventions

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.	Combination Product: 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)

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.

Combination Product: 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)

Outcome Measures

Primary Outcome Measures

Time to flare by Week 26, defined as time from randomization to the date of first flare occurring within the 26-week period, in the modified intent-to-treat population. [week 26]

Secondary Outcome Measures

Time to flare by Week 26 in the per-protocol population. [week 26]
Percentage of subjects who have completed the 26-week corticosteroid taper and who have a normal erythrocyte sedimentation rate. [week 26]
Percentage of subjects who have completed the 26-week corticosteroid taper and who have a normal c-reactive protein level. [week 26]
Percentage of subjects who have completed the 26-week corticosteroid taper and who have no signs or symptoms of GCA. [week 26]
Time to corticosteroid dose of zero mg/day. [through study completion up to 26 weeks]
Cumulative steroid dose at week 26 and at the end of the washout safety follow-up period. [through study completion up to 26 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Selected Inclusion Criteria:

Subjects with new-onset or relapsing/refractory GCA.
Westergren erythrocyte sedimentation rate > 30 mm/hour or c-reactive protein ≥ 1 mg/ dL.
Remission of GCA at or before Day 0.
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.
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:

Transplanted organs (except corneal transplant performed more than 3 months prior to randomization).
Concurrent enrollment in another interventional clinical study.
Treatment with non-biologic investigational drug therapy within 4 weeks or 5 half-lives of the study agent, whichever was longer, prior to screening.
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.
Treatment with alkylating agents within 12 weeks prior to screening.
Intramuscular, Intra-articular or IV corticosteroids within 4 weeks prior to screening.
Receipt of live (attenuated) vaccine within the 4 weeks before Day 0.
Treatment with hydroxychloroquine, cyclosporine A, azathioprine, cyclophosphamide, or mycophenolate mofetil (MMF) within 4 weeks of screening.
Female subjects who are pregnant, intending to become pregnant, or are breastfeeding.
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.
Positive (or 2 indeterminate) QuantiFERON test results.
Clinically significant active infection or infection requiring hospitalization or IV antibiotics within 12 weeks before screening or opportunistic infection within 6 months before screening.
Chronic active hepatitis B infection.
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.
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.
Evidence of clinically-uncontrolled respiratory disease.
History of chronic respiratory tract infections.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 1703	Sarasota	Florida	United States	34239
2	Site 1708	Tampa	Florida	United States	33612
3	Site 1706	Atlanta	Georgia	United States	30342
4	Site 1701	Boston	Massachusetts	United States	02114
5	Site 1704	Saint Clair Shores	Michigan	United States	48081
6	Site 1702	Rochester	Minnesota	United States	55905
7	Site 1705	New York	New York	United States	10021
8	Site 2102	Kogarah		Australia
9	Site 2106	Melbourne		Australia
10	Site 2105	Nedlands		Australia
11	Site 2101	Victoria Park		Australia
12	Site 2104	Woodville South		Australia
13	Site 2204	Brussels		Belgium
14	Site 2202	Leuven		Belgium	3000
15	Site 2201	Liège		Belgium	4000
16	Site 2203	Yvoir		Belgium
17	Site 2303	Zagreb		Croatia	10 000
18	Site 2401	Tallinn		Estonia
19	Site 2402	Tartu		Estonia
20	Site 2502	Tuebingen	Baden-Württemberg	Germany	72076
21	Site 2504	Erlangen	Bayern	Germany	91054
22	Site 2507	Freiburg		Germany	79106
23	Site 2503	Hannover		Germany	30625
24	Site 2508	Jena		Germany	7747
25	Site 2501	Kirchheim Unter Teck		Germany	73230
26	Site 2601	Dublin		Ireland	4
27	Site 2703	Milano		Italy
28	Site 2702	Reggio Emilia		Italy
29	Site 2701	Rozzano		Italy
30	Site 2704	Udine		Italy	33100
31	Site 2802	Groningen		Netherlands
32	Site 2801	Rotterdam		Netherlands
33	Site 2902	Christchurch		New Zealand
34	Site 2901	Wellington		New Zealand
35	Site 1002	Kraków		Poland	31-121
36	Site 1103	Belgrade		Serbia	11000
37	Site 1101	Belgrade		Serbia
38	Site 1102	Belgrade		Serbia
39	Site 1201	Ljubljana		Slovenia
40	Site 1303	A Coruña		Spain
41	Site 1301	Barcelona		Spain
42	Site 1304	Bilbao		Spain
43	Site 1302	Santa Cruz De Tenerife		Spain
44	Site 1604	Edinburgh		United Kingdom
45	Site 1602	Leytonstone		United Kingdom
46	Site 1601	Newcastle Upon Tyne		United Kingdom	NE7 7DN
47	Site 1603	Southend		United Kingdom