A Phase 1b Double-Blind, Randomized, Placebo-Controlled Study of the Safety, Pharmacokinetics and Pharmacodynamics of AC0058TA in Patients With Systemic Lupus Erythematosus (SLE)

ACEA Therapeutics, Inc.1 site in 1 country32 target enrollmentNovember 28, 2018

ConditionsSystemic Lupus Erythematosus

InterventionsAC0058TA Placebo AC0058TA

DrugsAC0058TA Placebo AC0058TA

Overview

Phase: Phase 1
Intervention: AC0058TA
Conditions: Systemic Lupus Erythematosus
Sponsor: ACEA Therapeutics, Inc.
Enrollment: 32
Locations: 1
Primary Endpoint: Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase 1b, double blind, randomized, placebo-controlled study of the safety and tolerability, pharmacokinetics and pharmacodynamics of AC0058TA in patients with systemic lupus erythematosus (SLE).

Detailed Description

The study will be performed in adult patients with autoantibody (ANA) positive SLE, as defined by the American College of Rheumatology (ACR) 1997 criteria or System Lupus International Collaborating Clinic (SLICC) 2009 criteria who are receiving standard of care therapy for SLE.

Registry

clinicaltrials.gov

Start Date

November 28, 2018

End Date

December 2021

Last Updated

7 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

ACEA Therapeutics, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Clinical diagnosis of SLE according to ACR 1997 criteria or 2009 SLE-SLICC criteria with ANA positive (≥ 1:40) patients who could receive hydroxychloroquine and/or steroids treatment.
•Adequate hematopoietic function, including:
•Platelet count \> 75 × 10\^9/L
•Leukocyte ≥ 2.0 × 10\^9/L including CD19+ B cell counts of at least 50/μL
•Hemoglobin ≥ 10 g/dL
•Adequate liver function
•Bilirubin: \< 1.2 X upper limit of normal (ULN)
•AST: \< 1.2 X upper limit of normal (ULN)
•ALT: \< 1.2 X upper limit of normal (ULN)
•Adequate renal function:

Exclusion Criteria

•Active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident \[CVA\], cerebritis or CNS vasculitis) or active bleeding disorder within 60 days prior to the first day of study treatment.
•Clinical evidence of significant unstable or uncontrolled acute or chronic diseases other than SLE which, in the opinion of the investigator, could confound the results of the study, put the patient at undue risk, or interferes with protocol adherence, or a subject's ability to give informed consent.
•History or presence of congestive heart failure (New York Heart Association \[NYHA\]Class III to IV), symptomatic ischemia, clinically significant conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months prior to the first day of study treatment.
•Have severe lupus complications (Acute Lupus Pneumonitis, Diffuse Alveolar Hemorrhage, Chronic Interstitial Pneumonia, Pulmonary Hypertension, Pulmonary Embolism) severe lupus gastrointestinal diseases (Lupus Mesenteric Vasculitis, Protein-Losing Enteropathy, Pancreatitis, Intestinal Pseudo-Obstruction).
•History of any bleeding disorder secondary to SLE.
•Have active, severe lupus kidney disease WHO III-V (Rapidly Progressive Glomerulonephritis, Nephrotic Syndrome, Renal Tubular Acidosis, Renal Insufficiency), proteinuria \> 500 mg/day.
•Acute or chronic infections requiring systemic antibiotic, antifungal, or antiviral therapy within 60 days of the first day of study treatment.
•Known HIV infection or positive for hepatitis B virus infection (HBsAg positive, HBeAg, HBeAb or HBcAb positive and HBV DNA positive) or hepatitis C antibody positive (HCV RNA positive).
•Primary immunodeficiency other than complement deficiencies.
•Active or latent tuberculosis within 6 months prior to the first day of study treatment.

Arms & Interventions

AC0058TA

AC0058TA will be administered in 25 mg capsules orally at the following doses: 50 mg QD, 100 mg QD, 200 mg QD and 100 mg BID

Intervention: AC0058TA

Placebo AC0058TA

Placebo AC0058TA will be administered orally at the equivalent dose of investigational product

Intervention: Placebo AC0058TA

Outcomes

Primary Outcomes

Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events

Time Frame: Measured up to 12 weeks

Secondary Outcomes

Pharmacodynamics of AC0058TA: Bruton's tyrosine kinase (BTK) occupancy (% occupancy)(Measured on Day 1, Day 28, and Day 84)
Pharmacodynamics of AC0058TA: serum antidsDNA antibodies, ANAs, complement (C3 and C4) and B-cell markers(Measured on Day 1, Day 28, and Day 84)
Maximum Plasma Concentration and Area Under the Curve(Measured on Day 1, Day 28, and Day 84)