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

Systemic Lupus Erythematosus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03817424
• Other study ID #: VIB7734.P1b.S1
• Secondary ID: 2018-003767-60
• Status: Completed
• Phase: Phase 1
• Start date: December 13, 2018
• Est. completion date: July 20, 2020

Study information

• Verified date: August 2020
• Source: Viela Bio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: July 20, 2020
• Est. primary completion date: July 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Participants aged 18 through 75 years at the time of screening

• Participants with at least one of the following diagnoses:

1. Systemic Lupus Erythematosus

2. Cutaneous lupus erythematosus, including acute CLE, subacute CLE, and discoid lupus erythematosus

3. Sjogren's syndrome (for Cohort 1 only)

4. Systemic sclerosis (for Cohort 1 only)

5. Probable or definite polymyositis (for Cohort 1 only)

6. 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

Related Conditions & MeSH terms

• Cutaneous Lupus Erythematosus
• Dermatomyositis
• Lupus Erythematosus, Cutaneous
• Lupus Erythematosus, Systemic
• Polymyositis
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Sjogren's Syndrome
• Syndrome
• Systemic Lupus Erythematosus
• Systemic Sclerosis

Intervention

Drug:
• VIB7734
Participants will receive VIB7734 via injection.
• Placebo
Participants will receive placebo matching to VIB7734 via injection.

Locations

Country	Name	City	State
Poland	Viela Bio Investigative Site	Bialystok
Poland	Viela Bio Investigative Site	Bydgoszcz
Poland	Viela Bio Investigative Site	Kraków
Poland	Viela Bio Investigative Site	Poznan
Poland	Viela Bio Investigative Site	Rzeszów
Poland	Viela Bio Investigative Site	Warsaw
Poland	Viela Bio Investigative Site	Wroclaw
Spain	Viela Bio Investigative Site	Barcelona
Spain	Viela Bio Investigative Site	Bilbao
Spain	Viela Bio Investigative Site	Madrid
Spain	Viela Bio Investigative Site	Sevilla
United States	Viela Bio Investigative Site	Allen	Texas
United States	Viela Bio Investigative Site	Anniston	Alabama
United States	Viela Bio Investigative Site	Birmingham	Alabama
United States	Viela Bio Investigative Site	Charlotte	North Carolina
United States	Viela Bio Investigative Site	Danbury	Connecticut
United States	Viela Bio Investigative Site	Duncansville	Pennsylvania
United States	Viela Bio Investigative Site	Durham	North Carolina
United States	Viela Bio Investigative Site	Fort Lauderdale	Florida
United States	Viela Bio Investigative Site	Great Neck	New York
United States	Viela Bio Investigative Site	Hialeah	Florida
United States	Viela Bio Investigative Site	Jacksonville	Florida
United States	Viela Bio Investigative Site	Lawrenceville	Georgia
United States	Viela Bio Investigative Site	Los Angeles	California
United States	Viela Bio Investigative Site	Memphis	Tennessee
United States	Viela Bio Investigative Site	Mesquite	Texas
United States	Viela Bio Investigative Site	Miami Lakes	Florida
United States	Viela Bio Investigative Site	Philadelphia	Pennsylvania
United States	Viela Bio Investigative Site	Saint Petersburg	Florida
United States	Viela Bio Investigative Site	Upland	California

Sponsors (1)

Lead Sponsor	Collaborator
Viela Bio

Countries where clinical trial is conducted

United States,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)		Day 1 up to Day 337
Primary	Number of Participants With Adverse Events of Special Interest (AESIs)		Day 1 up to Day 337
Primary	Number of Participants With Laboratory Abnormalities Reported as TEAEs		Day 1 up to Day 337
Primary	Number of Participants With Vital Sign Abnormalities Reported as TEAEs		Day 1 up to Day 337
Primary	Number of Participants With 12-Lead Electrocardiogram Abnormalities Reported as TEAEs		Day 1 up to Day 337
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of Participants With Positive Anti-Drug Antibodies of VIB7734		Day 1 up to Day 309
Secondary	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
Secondary	Blood Levels of pDCs		Day 1 up to Day 337