Clinical Trial: Autologous Polyclonal Tregs for Lupus

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase I, Open-Label, Dose Escalation Trial Exploring the Safety and Tolerability of Autologous Polyclonal Regulatory T Cell Therapy in Adults With Active Cutaneous Lupus (ALE08)

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.

Detailed Summary: The investigational therapy in this trial, regulatory T cells (Tregs), is evaluating an alternative to traditional immunosuppressive therapies for the treatment of systemic lupus erythematosus (SLE, lupus). Too frequently, aggressive therapies are inadequate in the control of the disease and have potent side effects and complications. The collection and expansion of one's own T cells harnesses a naturally occurring regulatory mechanism to restore self-tolerance in people with lupus. Tregs are a specialized subset of T cells that function to control the immune response. Studies have shown that in active lupus, the numbers and function of Treg cells are significantly decreased, which contributes to an overactive immune system and an increase in disease activity. The hope is that these naturally occurring Treg cells can be used for the treatment of autoimmune diseases, including lupus.
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome: Number of significant events in each cohort [ Time Frame: Week 48 ]

Defined as any related NCI-CTCAE Grade 3 or higher AE or any related SAE.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of Significant Events in Each Cohort [ Time Frame: Week 152 ]
    Defined as any related NCI-CTCAE Grade 3 or higher adverse events (AE) or any related SAE.
  • All Adverse Events (AEs) [ Time Frame: Week 152 ]
  • All NCI-CTCAE Grade 3-5 AEs [ Time Frame: Week 152 ]
  • All Serious Adverse Events (SAEs) [ Time Frame: Week 152 ]
  • All Infection Related Events [ Time Frame: Within 24 hours of infusion ]
  • All Lupus Flares [ Time Frame: Week 152 ]
    as defined by Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI)
  • All Infusion Reactions [ Time Frame: Week 152 ]
    Defined as any adverse reaction of NCI-CTCAE Grade 1 and higher within 24 hours of infusion
  • Absolute and Change from Baseline in Clinical Chemistry, Hematology, and Urinalysis After Treatment [ Time Frame: Week 152 ]
  • Change in CLASI Activity Score from Baseline [ Time Frame: Week 152 ]
    Cutaneous Lupus Erythematosus Disease Area and Severity Index
  • Change in Skindex-29 Scores from Baseline [ Time Frame: Week 152 ]
  • Change in SELENA-SLEDAI Total Score from Baseline [ Time Frame: Week 152 ]
  • Change in Patient Global Assessment (PGA) from Baseline [ Time Frame: Week 152 ]
  • Change in Physician Global Assessment (PhGA) from Baseline [ Time Frame: Week 152 ]
  • Change in Anti-dsDNA Antibody Titers from Baseline [ Time Frame: Week 152 ]
  • Change in Serum C3 and C4 Complement Levels from Baseline [ Time Frame: Week 152 ]


Original Secondary Outcome:

  • Number of Significant Events in Each Cohort [ Time Frame: Week 152 ]
    Defined as any related NCI-CTCAE Grade 3 or higher adverse events (AE) or any related SAE.
  • All AEs [ Time Frame: Week 152 ]
  • All NCI-CTCAE Grade 3-5 AEs [ Time Frame: Week 152 ]
  • All SAEs [ Time Frame: Week 152 ]
  • All Infection Related Events [ Time Frame: Week 152 ]
  • All Lupus Flares [ Time Frame: Week 152 ]
    as defined by Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI)
  • All Infusion Reactions [ Time Frame: Week 152 ]
    Defined as any adverse reaction of NCI-CTCAE Grade 1 and higher within 24 hours of infusion
  • Absolute and Change from Baseline in Clinical Chemistry, Hematology, and Urinalysis After Treatment [ Time Frame: Week 152 ]
  • Change in CLASI Activity Score from Baseline [ Time Frame: Week 152 ]
  • Change in Skindex-29 Scores from Baseline [ Time Frame: Week 152 ]
  • Change in SELENA-SLEDAI Total Score from Baseline [ Time Frame: Week 152 ]
  • Change in patient global assessment (PGA) form baseline [ Time Frame: Week 152 ]
  • Change in Physician Global Assessment (PhGA) from Baseline [ Time Frame: Week 152 ]
  • Change in Anti-dsDNA Antibody Titers from Baseline [ Time Frame: Week 152 ]
  • Change in serum C3 and C4 complement levels from baselin [ Time Frame: Week 152 ]


Information By: National Institute of Allergy and Infectious Diseases (NIAID)

Dates:
Date Received: April 23, 2015
Date Started: July 2015
Date Completion: January 2019
Last Updated: April 26, 2017
Last Verified: April 2017