Study of AC0058TA in Patients With Systemic Lupus Erythematosus (SLE)

NCT03878303 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: AC00582017-101
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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).

Conditions

Systemic Lupus Erythematosus

Keywords

SLE

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events

  Measured up to 12 weeks

Secondary Outcomes (3)

• Maximum Plasma Concentration and Area Under the Curve

  Measured on Day 1, Day 28, and Day 84

• 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

Study Arms (2)

AC0058TA

EXPERIMENTAL

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

Drug: AC0058TA

Placebo AC0058TA

PLACEBO COMPARATOR

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

Drug: Placebo AC0058TA

Interventions

AC0058TA DRUG

25 mg capsules

Also known as: AC0058

AC0058TA

Placebo AC0058TA DRUG

equivalent dose of investigational product

Also known as: Placebo

Placebo AC0058TA

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• a. BUN and creatinine:\< 1.5 X upper limit of normal (ULN)
• Female of reproductive potential must agree to use two forms of contraception during screening, during the study, and for at least 30 days after the last dose of AC0058TA.
• Able to provide written informed consent in accordance with federal, local, and institutional guidelines.

You may not qualify if:

• 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.
• Receipt of a live-attenuated vaccine within 2 months prior to screening.
• Within 2 weeks prior to screening：Use of injectable corticosteroids.
• Within 2 months prior to screening: use of abatacept, anti-tumor necrosis factor alpha agents, intravenous immunoglobulin, plasmapheresis, mycophenolate, MTX and leflunomide or therapies not otherwise specified in protocol.
• Use of cyclophosphamide or chlorambucil within five half-lives of screening.
• Use of rituximab, belimumab, or any other B cell-depleting or modulating therapies within 6 months of screening.

Sponsors & Collaborators

• ACEA Therapeutics, Inc.: lead
• Hangzhou ACEA Pharmaceutical Research Co., Ltd.: collaborator

Study Sites (1)

Metroplex Clinical Research Center

Dallas, Texas, 75231, United States

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Roy Fleischmann, MD MACR

  Metroplex Clinical Research Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liming Liu, MD, PhD

CONTACT

1-858-249-9120; limingliu@aceatherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2019
• First Posted: March 18, 2019
• Study Start: November 28, 2018
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2021
• Last Updated: March 18, 2019

Record last verified: 2019-03

Locations

US (1)