Autologous Polyclonal Tregs for Lupus

NCT02428309 | Terminated Phase 1 Results DMC

• 1 other identifier: DAIT ALE08
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this Phase 1 study is to evaluate the safety, tolerability, and effect of 3 different doses of Treg therapy in adults with skin (cutaneous) involvement of their lupus. Targeting cutaneous disease offers the ability to control background therapy, readily detect clinical effects, and perform research analyses not only in blood but also skin. Safety, disease activity, and mechanism of Tregs will be evaluated. The intent is to support dose selection for a future larger efficacy trial in lupus.

Conditions

Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic

Keywords

active cutaneous lupus; systemic lupus erythematosus (SLE); autologous polyclonal regulatory T cell Therapy; polyclonal Tregs for treatment of lupus

Outcome Measures

Primary Outcomes (1)

• Number of Significant Adverse Events (AEs) Through Week 48

  A significant adverse event is any related National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.0 Grade 3 or higher AE or any related serious adverse event. Related is defined as being possibly, probably, or definitely related to the ex vivo expanded autologous PolyTregs, as determined by the safety review committee.

  From time of signed informed consent to Week 48

Secondary Outcomes (19)

• Number of Significant Adverse Events (AEs) Through Week 152

  From time of signed informed consent to Week 152

• Number of Grade 3 or Higher Adverse Events (AEs) Through Week 152

  From time of signed informed consent to Week 152

• Number of Infection-Related Adverse Events (AEs) Through Week 152

  From time of signed informed consent to Week 152

• Number of Lupus Flares Through Week 152 by Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Criteria

  From time of signed informed consent to Week 152

• Number Infusion-Related Adverse Events (AEs) Within 24 Hours of Infusion

  From time of infusion to 24 hours post infusion

Study Arms (3)

Low Dose Treg Cohort

EXPERIMENTAL

3-6 participants will receive a single infusion of 1 x 10\^ 8 autologous polyclonal Tregs (ex vivo selected and expanded)

Biological: Ex vivo Expanded Human Autologous Polyclonal Regulatory T Cells

Medium Dose Treg Cohort

EXPERIMENTAL

Sequential dose escalation, 3-6 subjects will receive a single infusion of 4 x 10\^ 8 autologous polyclonal Tregs (ex vivo selected and expanded)

Biological: Ex vivo Expanded Human Autologous Polyclonal Regulatory T Cells

High Dose Treg Cohort

EXPERIMENTAL

Sequential dose escalation, 3-6 participants will receive a single infusion of 16 x 10\^ 8 autologous polyclonal Tregs (ex vivo selected and expanded)

Biological: Ex vivo Expanded Human Autologous Polyclonal Regulatory T Cells

Interventions

Ex vivo Expanded Human Autologous Polyclonal Regulatory T Cells BIOLOGICAL

Also known as: Ex vivo Expanded Autologous CD4+CD127lo/-CD25+ Polyclonal Regulatory T Cells

High Dose Treg Cohort; Low Dose Treg Cohort; Medium Dose Treg Cohort

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Ability to provide informed consent.
• Diagnosis of SLE by American College of Rheumatology (ACR) criteria or biopsy proven primary cutaneous lupus.
• Presence of ≥ 2 active cutaneous lupus lesions based on (1) visual morphology and (2) at least a grade 2 erythema on CLASI activity score. Histopathologic confirmation is required unless the active lesions are of the same morphology to previously histologically proven cutaneous lupus lesions.
• The cutaneous lupus lesions must include any of the following subtypes:
• Acute cutaneous lupus including maculopapular lupus rash and photosensitive lupus rash,
• Subacute cutaneous lupus,
• Chronic cutaneous lupus including discoid lupus and hypertrophic (verrucous) lupus,
• Lupus timidus
• Positive test for Epstein-Barr virus (EBV) antibody.
• Adequate venous access to support draw of 400 mL whole blood and infusion of investigational therapy.

You may not qualify if:

• New onset of cutaneous lupus which has not been treated with broad spectrum sunscreen (UVA and UVB) in combination with either antimalarials or another systemic medication for at least 3 months.
• Prednisone dose \> 15mg/day within the 30 days prior to screening.
• Addition of a new medication, or change in the dose of any background medication, used to treat any aspect of SLE. Specifically:
• addition or change in systemic glucocorticoids, antimalarials, methotrexate, mycophenolate mofetil, mycophenolic acid, azathioprine, cyclosporine, tacrolimus, thalidomide, lenalidomide, dapsone, acitretin, or isotretinoin within 90 days prior to screening
• treatment with cyclophosphamide within 90 days prior to screening.
• Doses of background medications at Screening visit:
• hydroxychloroquine \> 400 mg/day,
• chloroquine \> 250 mg/day,
• quinacrine \>100 mg/day,
• methotrexate \> 25 mg/week,
• mycophenolate mofetil (MMF)\> 3000 mg/day,
• mycophenolic acid \> 720 mg/day BID,
• azathioprine \> 200 mg/day,
• cyclosporine \> 5 mg/day divided BID,
• tacrolimus \> 6 mg/day

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Autoimmunity Centers of Excellence: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)
• Autoimmunity Centers of Excellence

MeSH Terms

Conditions

Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

The study terminated early due to recruitment feasibility issues. One participant was enrolled, received polyclonal Treg treatment and was followed through week 152, per protocol.

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• Maria Dall'Era, MD

  University of California, San Francisco

  STUDY CHAIR

• Anna Haemel, MD

  University of California, San Francisco

  STUDY CHAIR

• Jeffrey Bluestone, PhD

  University of California, San Francisco

  STUDY CHAIR

• Michael Rosenblum, MD, PhD

  University of California, San Francisco

  STUDY CHAIR

• David Wofsy, MD

  University of California, San Francisco

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2015
• First Posted: April 28, 2015
• Study Start: August 27, 2015
• Primary Completion: September 2, 2016
• Study Completion: October 3, 2018
• Last Updated: November 12, 2019
• Results First Posted: November 12, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will share
• Time Frame: The aim is to share data available to the public within 24 months upon completion of the study.
• Access Criteria: Will be available to the public.

Locations

US (1)