A Study to Evaluate VIB7734 in Participants With Systemic Lupus Erythematosus (SLE), Cutaneous Lupus Erythematosus (CLE), Sjogren's Syndrome, Systemic Sclerosis, Polymyositis, and Dermatomyositis

Sponsor

Viela Bio (Industry)

Overall Status

Completed

CT.gov ID

NCT03817424

Collaborator

(none)

Enrollment

Locations

Arms

19.2

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of escalating, multiple subcutaneous (SC) doses of VIB7734 in participants with Systemic Lupus Erythematosus (SLE), Cutaneous Lupus Erythematosus (CLE), Sjogren's Syndrome, Systemic Sclerosis, Polymyositis, and Dermatomyositis.

Condition or Disease	Intervention/Treatment	Phase
Systemic Lupus Erythematosus Cutaneous Lupus Erythematosus Sjogren's Syndrome Systemic Sclerosis Polymyositis Dermatomyositis	Drug: VIB7734 Drug: Placebo	Phase 1

Detailed Description

This study will have 3 periods: screening, treatment period, and extended follow-up. The screening period is 28 days. A total of 32 participants will be enrolled in 3 cohorts with 8 participants in Cohort 1, and 12 participants each in Cohorts 2 and 3. In Cohort 1, participants will be randomized in a 3:1 ratio to receive VIB7734 or matching placebo by injection every 4 weeks (q4w) for a total of 3 doses on Days 1, 29, and 57. In Cohorts 2 and 3, participants diagnosed with lupus only will be randomized in a 2:1 ratio to receive VIB7734 or matching placebo by injection q4w for 3 doses on Days 1, 29, and 57. Participants will be followed until at least Day 141. After the Day 141 visit, participants will exit the study if participants meets adequate plasmacytoid dendritic cells (pDCs). If an adequate pDC level does not meet at Day 141 visit, the participant will continue the follow-up for pDC repletion until they meet the protocol defined adequate pDC level or Day 337 visit has been reached.

Study Design

Study Type:

Interventional

Actual Enrollment :

31 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Randomized, Placebo-Controlled, Blinded, Multiple Ascending Dose Study to Evaluate VIB7734 in Systemic Lupus Erythematosus, Cutaneous Lupus Erythematosus, Sjogren's Syndrome, Systemic Sclerosis, Polymyositis, and Dermatomyositis

Actual Study Start Date :

Dec 13, 2018

Actual Primary Completion Date :

Jul 20, 2020

Actual Study Completion Date :

Jul 20, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: VIB7734 Dose 1 Participants will receive VIB7734 Dose 1 via injection q4w for a total of 3 doses on Days 1, 29, and 57.	Drug: VIB7734 Participants will receive VIB7734 via injection. Other Names: MEDI7734
Experimental: Cohort 2: VIB7734 Dose 2 Participants will receive VIB7734 Dose 2 via injection q4w for a total of 3 doses on Days 1, 29, and 57.	Drug: VIB7734 Participants will receive VIB7734 via injection. Other Names: MEDI7734
Experimental: Cohort 3: VIB7734 Dose 3 Participants will receive VIB7734 Dose 3 via injection q4w for a total of 3 doses on Days 1, 29, and 57.	Drug: VIB7734 Participants will receive VIB7734 via injection. Other Names: MEDI7734
Placebo Comparator: Placebo Participants will receive placebo matching to VIB7734 via injection q4w for a total of 3 doses on Days 1, 29, and 57.	Drug: Placebo Participants will receive placebo matching to VIB7734 via injection.

Outcome Measures

Primary Outcome Measures

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [Day 1 up to Day 337]
Number of Participants With Adverse Events of Special Interest (AESIs) [Day 1 up to Day 337]
Number of Participants With Laboratory Abnormalities Reported as TEAEs [Day 1 up to Day 337]
Number of Participants With Vital Sign Abnormalities Reported as TEAEs [Day 1 up to Day 337]
Number of Participants With 12-Lead Electrocardiogram Abnormalities Reported as TEAEs [Day 1 up to Day 337]

Secondary Outcome Measures

Maximum Observed Serum Concentration (Cmax) of VIB7734 Maximum Observed Serum Concentration (Cmax) of VIB7734 [Days 1 (pre-dose), 8, 15, 29 (pre-dose), 36, 43, 57 (pre-dose), 64, 71, 85, 113, 141, 169, 197, 225, and 253]
Area Under the Concentration-time Curve (AUC) of VIB7734 [Days 1 (pre-dose), 8, 15, 29 (pre-dose), 36, 43, 57 (pre-dose), 64, 71, 85, 113, 141, 169, 197, 225, and 253]
Systemic Clearance (CL) of VIB7734 [Days 1 (pre-dose), 8, 15, 29 (pre-dose), 36, 43, 57 (pre-dose), 64, 71, 85, 113, 141, 169, 197, 225, and 253]
Terminal Half-life (t1/2) of VIB7734 [Days 1 (pre-dose), 8, 15, 29 (pre-dose), 36, 43, 57 (pre-dose), 64, 71, 85, 113, 141, 169, 197, 225, and 253]
Number of Participants With Positive Anti-Drug Antibodies of VIB7734 [Day 1 up to Day 309]
Change from Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score (Cohorts 2 and 3) [Day 1 up to Day 253]
Blood Levels of pDCs [Day 1 up to Day 337]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants aged 18 through 75 years at the time of screening
Participants with at least one of the following diagnoses:

Systemic Lupus Erythematosus
Cutaneous lupus erythematosus, including acute CLE, subacute CLE, and discoid lupus erythematosus
Sjogren's syndrome (for Cohort 1 only)
Systemic sclerosis (for Cohort 1 only)
Probable or definite polymyositis (for Cohort 1 only)
Probable or definite dermatomyositis (for Cohort 1 only)

For Cohorts 2 and 3 only: Participants with CLASI activity score greater than or equal to (>=) 8 at both Visits 1 (screening) and 2 (baseline)
For Cohorts 2 and 3 only: a skin lesion amenable to punch skin biopsy and willingness of the participant to undergo skin biopsy at two time points
For Cohorts 2 and 3 only: photographs of skin lesions must be submitted for review to confirm the diagnosis of SLE or CLE with active skin lesions confirmation of the diagnosis by the central reviewer must be received prior to randomization
Females of childbearing potential and nonsterilized males who are ready to use protocol defined contraception methods

Exclusion Criteria:

Severe manifestations of the diseases under study that could impact the participant safety
Known history of a primary immunodeficiency or an underlying condition such as known human immunodeficiency virus (HIV) infection, a positive result for HIV infection, splenectomy, or any underlying condition that predisposes the participant to infection
At screening, have adequate central laboratory test results: aspartate transaminase greater than (>) 2.5 x upper limit of normal (ULN); alanine transaminase >2.5 x ULN; total bilirubin 1.5 x ULN; total immunoglobulin < 500 gram/decilitre; neutrophil count less than (<) 1,000/μL; platelet count < 85,000/μL; haemoglobin < 10 g/dL; glycosylated haemoglobin > 8 percent (%); total lymphocyte count < 300 cells/mm^{3;
glomerular filtration rate < 50 mL/min/1.73 m}2; plasmacytoid dendritic cells (pDC) level < 0.02% of peripheral blood mononuclear cells (PBMCs)
Positive test for chronic hepatitis B infection at screening and for hepatitis C virus antibody
History of or active tuberculosis (TB), or a positive QuantiFERON®-TB Gold test at screening; a primary immunodeficiency or an underlying condition such as known human immunodeficiency virus (HIV) infection, a positive result for HIV infection per central laboratory; cancer; clinically significant cardiac disease
Herpes zoster infection within 3 months before randomization and/or any severe herpes virus family infection at any time prior to randomization
Any acute illness or evidence of clinically significant active infection, such as fever >= 38.0 degrees Celsius (>= 100.5 degrees Fahrenheit) at screening (Visit 1) or Day 1 (Visit 2)
Cohorts 2 and 3 only: use of Group 1 (super-high potency) or Group 2 (high potency) topical corticosteroids
Receipt of a live-attenuated vaccine within 4 weeks prior to Day 1
Cohorts 2 and 3 only: have received changing doses of mycophenolate mofetil, methotrexate, leflunomide, azathioprine, or non-steroidal topical immunosuppressants within 28 days before study Day 1 or changing doses of oral or topical corticosteroids within 14 days before study Day 1

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Viela Bio Investigative Site	Anniston	Alabama	United States	36201
2	Viela Bio Investigative Site	Birmingham	Alabama	United States	35294
3	Viela Bio Investigative Site	Los Angeles	California	United States	90022
4	Viela Bio Investigative Site	Upland	California	United States	91786
5	Viela Bio Investigative Site	Danbury	Connecticut	United States	06810
6	Viela Bio Investigative Site	Fort Lauderdale	Florida	United States	33309
7	Viela Bio Investigative Site	Hialeah	Florida	United States	33016
8	Viela Bio Investigative Site	Jacksonville	Florida	United States	32216
9	Viela Bio Investigative Site	Miami Lakes	Florida	United States	33014
10	Viela Bio Investigative Site	Saint Petersburg	Florida	United States	33710
11	Viela Bio Investigative Site	Lawrenceville	Georgia	United States	30046
12	Viela Bio Investigative Site	Great Neck	New York	United States	11021
13	Viela Bio Investigative Site	Charlotte	North Carolina	United States	28204
14	Viela Bio Investigative Site	Durham	North Carolina	United States	27713
15	Viela Bio Investigative Site	Duncansville	Pennsylvania	United States	16635
16	Viela Bio Investigative Site	Philadelphia	Pennsylvania	United States	19104
17	Viela Bio Investigative Site	Memphis	Tennessee	United States	38119
18	Viela Bio Investigative Site	Allen	Texas	United States	75013
19	Viela Bio Investigative Site	Mesquite	Texas	United States	75150
20	Viela Bio Investigative Site	Białystok		Poland
21	Viela Bio Investigative Site	Bydgoszcz		Poland
22	Viela Bio Investigative Site	Kraków		Poland
23	Viela Bio Investigative Site	Poznań		Poland
24	Viela Bio Investigative Site	Rzeszów		Poland
25	Viela Bio Investigative Site	Warsaw		Poland
26	Viela Bio Investigative Site	Wrocław		Poland
27	Viela Bio Investigative Site	Barcelona		Spain
28	Viela Bio Investigative Site	Bilbao		Spain
29	Viela Bio Investigative Site	Madrid		Spain
30	Viela Bio Investigative Site	Sevilla		Spain