KPL-301 for Subjects With Giant Cell Arteritis | NCT03827018

NCT03827018

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
mavrilimumab	Active Comparator	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 Drug: prednisone
placebo	Placebo Comparator	Subjects randomized to placebo will receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	Combination Product: placebo Drug: prednisone

Name	Type	Description	Arm Group Labels	Other Names
mavrilimumab	Combination Product	1 mL of 150 mg in a pre-filled syringe	mavrilimumab

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Eligibility Module

Eligibility Criteria

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/Locations Module

Name	Affiliation	Role
John Paolini, M.D.	Kiniksa Pharmaceuticals, Ltd.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Site 1703		Sarasota	Florida	34239	United States
Site 1708

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35264321	Derived	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.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Mavrilimumab	Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
FG001	Placebo

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 30, 2020	Oct 17, 2023

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Mavrilimumab	Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
BG001	Placebo	Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00069.7± 6.98 BG00169.7± 8.31 BG00269.7± 7.48

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00032 BG00118 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
White	BG00040 BG00128 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0001 BG0012 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

Modified Intent to Treat (mITT) Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period.

Posted

Median

95% Confidence Interval

weeks

Week 26

ID	Title	Description
OG000	Mavrilimumab	Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
OG001	Placebo	Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.

Units	Counts
Participants	OG00042 OG00128

Title

Denominators

Categories

Title	Measurements
	OG000NA(NA to NA)Not estimable per Kaplan-Meier method (insufficient number of subjects with events) OG00125.1(16.0 to NA)Not estimable per Kaplan-Meier method (insufficient number of subjects with events)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.0263	Comparison of KPL-301 and placebo with respect to time to flare calculated by using a log-rank test stratified by randomization strata.	Hazard Ratio (HR)	0.38			2-Sided	95	0.15	0.92			95% confidence interval was calculated based on a Cox proportional-hazards model with treatment as covariate and stratified by randomization strata.		Superiority

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.

mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period.

Posted

Number

95% Confidence Interval

percentage of participants

Week 26

ID	Title	Description
OG000	Mavrilimumab	Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
OG001	Placebo	Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.

Units	Counts
Participants

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.

mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period. Participants with elevated ESR within 3 days of first dose are excluded from the analysis.

Posted

Median

95% Confidence Interval

weeks

Week 26

ID	Title	Description
OG000	Mavrilimumab	Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
OG001	Placebo	Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.

Units	Counts
Participants

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.

mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period. Participants with elevated CRP within 3 days of first dose are excluded from the analysis.

Posted

Median

95% Confidence Interval

weeks

Week 26

ID	Title	Description
OG000	Mavrilimumab	Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
OG001	Placebo	Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.

Units	Counts
Participants

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.

mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period.

Posted

Median

95% Confidence Interval

weeks

Week 26

ID	Title	Description
OG000	Mavrilimumab	Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
OG001	Placebo	Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.

Units	Counts
Participants	OG000

Secondary

Cumulative Corticosteroid Dose at Week 26

mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period.

Posted

Mean

Standard Deviation

Week 26

ID	Title	Description
OG000	Mavrilimumab	Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
OG001	Placebo	Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.

Units	Counts
Participants	OG000

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.

mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period.

Posted

Number

95% Confidence Interval

percentage of participants

Week 26

ID	Title	Description
OG000	Mavrilimumab	Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
OG001	Placebo	Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.

Units	Counts
Participants

Secondary

Percentage of Participants Who Completed the 26-Week Corticosteroid Taper and Who Had a Normal CRP Level

mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period.

Posted

Number

95% Confidence Interval

percentage of participants

Week 26

ID	Title	Description
OG000	Mavrilimumab	Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
OG001	Placebo	Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.

Units	Counts
Participants

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

mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period.

Posted

Number

95% Confidence Interval

percentage of participants

Week 26

ID	Title	Description
OG000	Mavrilimumab	Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
OG001	Placebo	Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.

Units	Counts
Participants

Secondary

Cumulative Corticosteroid Dose at the End of the Washout Safety Follow-up Period

mITT Analysis Set: all randomized participants who received at least 1 dose of mavrilimumab or placebo and had at least 1 assessment in the double-blind treatment period.

Posted

Mean

Standard Deviation

Final Safety Follow-up visit (Week 38)

ID	Title	Description
OG000	Mavrilimumab	Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.
OG001	Placebo	Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Mavrilimumab	Participants randomized to mavrilimumab receive 150 mg every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	0	42	2	42	33	42
EG001	Placebo	Participants randomized to placebo receive placebo every other week by subcutaneous injection co-administered with a 26-week corticosteroid taper.	0	28	3	28	25	28

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypertrophic cardiomyopathy	Congenital, familial and genetic disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected42 at risk EG0010 affected28 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected42 at risk EG0011 affected28 at risk
Oedema peripheral	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected42 at risk EG0011 affected28 at risk
Dementia	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected42 at risk EG0010 affected28 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected42 at risk EG0011 affected28 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected42 at risk EG0010 affected28 at risk
Diarrhea	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected42 at risk EG0013 affected28 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected42 at risk EG0012 affected28 at risk
Oedema peripheral	General disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected42 at risk EG0012 affected28 at risk
Pyrexia	General disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected42 at risk EG0012 affected28 at risk
Nasopharyngitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0005 affected42 at risk EG0013 affected28 at risk
Oral herpes	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected42 at risk EG0012 affected28 at risk
Respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0000 affected42 at risk EG0012 affected28 at risk
Rhinitis	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0001 affected42 at risk EG0012 affected28 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 21.0	Systematic Assessment	EG0003 affected42 at risk EG0012 affected28 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 21.0	Systematic Assessment	EG0002 affected42 at risk EG0015 affected28 at risk
Carbon monoxide diffusing capacity decreased	Investigations	MedDRA 21.0	Systematic Assessment	EG0004 affected42 at risk EG0011 affected28 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected42 at risk EG0012 affected28 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0002 affected42 at risk EG0014 affected28 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected42 at risk EG0013 affected28 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0003 affected42 at risk EG0013 affected28 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected42 at risk EG0012 affected28 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0004 affected42 at risk EG0012 affected28 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected42 at risk EG0012 affected28 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected42 at risk EG0012 affected28 at risk
Headache	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0006 affected42 at risk EG0017 affected28 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected42 at risk EG0012 affected28 at risk
Sleep disorder	Psychiatric disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected42 at risk EG0012 affected28 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 21.0	Systematic Assessment	EG0000 affected42 at risk EG0012 affected28 at risk
Hypertension	Vascular disorders	MedDRA 21.0	Systematic Assessment	EG0001 affected42 at risk EG0014 affected28 at risk

First MCP Posted Date

ID	Term
D013700	Giant Cell Arteritis

Ancestor Terms

ID	Term
D020293	Vasculitis, Central Nervous System
D020274	Autoimmune Diseases of the Nervous System
D009422	Nervous System Diseases
D002561	Cerebrovascular Disorders
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D001167	Arteritis
D014657	Vasculitis
D017445	Skin Diseases, Vascular
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
C561644	mavrilimumab
D011241	Prednisone

ID	Term
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds