An Open-label Study to Evaluate the Long-term Safety of MEDI-546, for the Treatment of SLE, in Adults

A Phase 2, Open-label Extension Study to Evaluate Long-term Safety of MEDI-546 in Adults With Systemic Lupus Erythematosus

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01753193

Enrollment

218

Registered

2012-12-20

Start date

2013-03-28

Completion date

2018-07-18

Last updated

2019-07-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lupus Erythematosus, Systemic

Keywords

Systemic Lupus Erythematosus

Brief summary

The purpose of this study is to evaluate the long-term safety of anifrolumab (MEDI-546) in adults with moderate to severe active systemic lupus erythematosus (SLE).

Detailed description

This is an open-label extension study to evaluate long-term safety and tolerability of intravenous (IV) anifrolumab in adult participants with moderately-to-severely active SLE. Participants must have completed the qualifying Phase 2 study and meet this study criteria in order to be eligible.

Interventions

BIOLOGICALAnifrolumab

Intravenous infusion of anifrolumab will be administered as 1000 mg Q4W from Day 1 (Week 0) until 12-Feb-2015 (approval of protocol amendment 4); and thereafter 300 mg Q4W up to 3 years or until the sponsor discontinued development of anifrolumab, whichever came first.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

This is an Open Label Extension study.

Eligibility

Sex/Gender

ALL

Age

18 Years to 68 Years

Healthy volunteers

Inclusion criteria

* Must be willing to use 2 methods of effective contraception * Must have venous access * Must be willing to forego participation in other clinical trials for SLE.

Exclusion criteria

* Any concurrent condition that in the opinion of the investigator would interfere with the evaluation of the investigational product * Major surgery within 8 weeks before signing informed consent form (ICF) * Elective major surgery planned during the study period * Concomitant Medications within the last 12 weeks: Azathioprine \> 200 mg/day, Mycophenolate mofetil/mycophenolic acid \> 2.0 g/day, oral, subcutaneous, or intramuscular methotrexate \> 25 mg/week * A live or attenuated vaccine within 4 weeks of signing the ICF * Bacillus of Calmette and Guérin (BCG) vaccine within 1 year of ICF

Design outcomes

Primary

Measure	Time frame	Description
Number of Particpants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	From first dose of study drug (Day 1) through 168 weeks	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Number of Participants With Adverse Events Resulting in Discontinuation (DAEs) of Anifrolumab	From first dose of study drug (Day 1) through 168 weeks	Number of participants with DAEs are reported.
Number of Participants With Adverse Events of Special Interest (AESIs)	From first dose of study drug (Day 1) through 168 weeks	An AESI is scientific and medical concern specific to understanding of the study drug. An AESI may be serious or non-serious. Number of participants with AESIs are reported.

Secondary

Measure	Time frame	Description
Number of ADA-positive Participants With Decreased Pharmacodynamics Response of Anifrolumab	Baseline (Pre-dose on Day 1) up to Week 168	Number of participants with decreased pharmacodynamic response of anifrolumab due to ADA-positive results are reported.
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Anifrolumab	Baseline (Pre-dose on Day 1) up to Week 168	The number of participants with positive serum antibodies to anifrolumab at anytime (including baseline) are reported.
Number of ADA-positive Participants With TEAEs and TESAEs	Baseline (Pre-dose on Day 1) up to Week 168	The number of ADA-positive participants with TEAEs and TESAEs are reported.
Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Global Score for ADA Positive Participants	Baseline (Pre-dose on Day 1); and Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 160, and 168	The SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms).
Anti-Drug Antibodies (ADA) Titer to Anifrolumab	Baseline (Pre-dose on Day 1) up to Week 168	Median ADA titer in participants with ADA-positive assessments and reportable ADA titer results are reported.
Number of ADA-positive Participants With Decreased Serum Concentration of Anifrolumab	Baseline (Pre-dose on Day 1) up to Week 168	Number of participants with decreased serum concentration of anifrolumab due to ADA-positive results are reported.

Countries

Brazil, Bulgaria, Colombia, Czechia, Hungary, Mexico, Peru, Poland, Romania, South Korea, Taiwan, Ukraine, United States

Participant flow

Recruitment details

The study was conducted from 28 Mar 2013 to 18 Jul 2018.

Pre-assignment details

A total of 218 participants were enrolled in this open-label extension (OLE) study.

Participants by arm

Arm	Count
Anifrolumab Participants received intravenous (IV) infusion of anifrolumab (MEDI-546) 1000 milligrams (mg) every 4 weeks (Q4W) from Day 1 (Week 0) until 12-Feb-2015 (approval of protocol amendment 4); and thereafter received 300 mg Q4W for up to 3 years or until the sponsor discontinued development of anifrolumab, whichever came first.	218
Total	218

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	1
Overall Study	Lost to Follow-up	6
Overall Study	Other	16
Overall Study	Withdrawal by Subject	23

Baseline characteristics

Characteristic	Anifrolumab
Age, Continuous	40.8 Years STANDARD_DEVIATION 12.2
Ethnicity (NIH/OMB) Hispanic or Latino	104 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	114 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants
Race (NIH/OMB) Asian	11 Participants
Race (NIH/OMB) Black or African American	29 Participants
Race (NIH/OMB) More than one race	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	85 Participants
Race (NIH/OMB) White	87 Participants
Sex: Female, Male Female	203 Participants
Sex: Female, Male Male	15 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	1 / 218
other Total, other adverse events	164 / 218
serious Total, serious adverse events	50 / 218

Outcome results

Primary

Number of Participants With Adverse Events of Special Interest (AESIs)

An AESI is scientific and medical concern specific to understanding of the study drug. An AESI may be serious or non-serious. Number of participants with AESIs are reported.

Time frame: From first dose of study drug (Day 1) through 168 weeks

Population: As-treated population included all participants who received any dose of study drug in the OLE study.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Anifrolumab	Number of Participants With Adverse Events of Special Interest (AESIs)	Nausea	1 Participants
Anifrolumab	Number of Participants With Adverse Events of Special Interest (AESIs)	Herpes zoster	11 Participants
Anifrolumab	Number of Participants With Adverse Events of Special Interest (AESIs)	Drug hypersensitivity	1 Participants
Anifrolumab	Number of Participants With Adverse Events of Special Interest (AESIs)	Hypersensitivity	2 Participants
Anifrolumab	Number of Participants With Adverse Events of Special Interest (AESIs)	Infusion related reaction	4 Participants
Anifrolumab	Number of Participants With Adverse Events of Special Interest (AESIs)	Hodgkin's disease	1 Participants
Anifrolumab	Number of Participants With Adverse Events of Special Interest (AESIs)	Latent tuberculosis	5 Participants
Anifrolumab	Number of Participants With Adverse Events of Special Interest (AESIs)	Hypersensitivity vasculitis	1 Participants
Anifrolumab	Number of Participants With Adverse Events of Special Interest (AESIs)	Vasculitis	1 Participants

Primary

Number of Participants With Adverse Events Resulting in Discontinuation (DAEs) of Anifrolumab

Number of participants with DAEs are reported.

Time frame: From first dose of study drug (Day 1) through 168 weeks

Population: As-treated population included all participants who received any dose of study drug in the OLE study.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Anifrolumab	Number of Participants With Adverse Events Resulting in Discontinuation (DAEs) of Anifrolumab	17 Participants

Primary

Number of Particpants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

Time frame: From first dose of study drug (Day 1) through 168 weeks

Population: As-treated population included all participants who received any dose of study drug in the OLE study.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Anifrolumab	Number of Particpants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TEAEs	170 Participants
Anifrolumab	Number of Particpants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	TESAEs	50 Participants

Secondary

Anti-Drug Antibodies (ADA) Titer to Anifrolumab

Median ADA titer in participants with ADA-positive assessments and reportable ADA titer results are reported.