Table 3.
Clinical trials involving tolerogenic dendritic cells in SLE.
| Drug/ Biologics |
Sponsors/ Clinical Trial No. |
Year | Study Population | Summary of Results | Challenges/ Future Development |
Ref. |
|---|---|---|---|---|---|---|
| Edratide (hCDR1) | Teva Pharmaceutical industries/ NCT00203151 |
Sep 2005–Feb 2007 | Phase II trial in Patients with active SLE (N = 340) | -The primary endpoints based solely on SLEDAI-2K and AMS were not met. -Improved BILAG, the Composite SLE Responder Index |
-Need more clinical study to confirm result | The Prelude study |
| Abatacept (CTLA4-Ig) | NIAID/NCT00774852 | Nov 2008–June 2014 | Phase II add-on trial in active lupus nephritis (N = 134) | -No statistically significant differences in % complete response at 24 or 52 weeks | -Might need to test with higher dose | The Access Trial Group [158] |
| Bristol-Myers Squibb/ NCT01714817 |
Jan 2013–May 2018 | 2-year long-term extension phase III trial in 405 patients with active class III or IV lupus nephritis | -No statistically significant differences in % complete renal response which is primary outcome -Earlier and more robust response |
-Might be useful in different subset of SLE patients | The Allure trial | |
| BG9588 (Anti-CD40L Antibody) | NIAMS/ NCT00001789 |
June 1999–May 2000 | Phase I trial in lupus nephritis patients (N = 28) | -Terminated due to thromboembolic events -A short course of treatment showed some clinical improvement |
-Additional studies will be needed to solve the issue of drug safety before evaluate its long-term effects | [160] |
| BIIB059 (humanized mAb to BDCA2) | Biogen/ NCT02106897 |
April 2014–May 2016 | First in human trial Healthy control (N = 54), SLE with active skin lesions (N = 12) |
-Favorable safety and PK profiles -Decreased expression of IFN response genes in blood -Reduced immune infiltrates in skin lesions |
-Support the important role of pDC as target for skin manifestation | [164] |
| Biogen/ NCT02847598 |
Oct 2016–Aug 2019 | Phase II clinical trial in SLE patients with active skin manifestations and CLE patients (N = 264) | No result posted yet | |||
| Thiazolidinediones (TZD) (PPARγ agonist) | NIAMS/ NCT02338999 |
Jan 015 Status: Active |
SLE patients, Plan to enroll 88 participants | No result posted yet | ||
| Laquinimod (AhR agonist) | Teva Pharmaceutical industries/ NCT01085084 |
July 2010–Dec 2012 | Phase II clinical trial in SLE with active lupus arthritis (N = 82) | No result posted yet | ||
| Teva Pharmaceutical industries/ NCT01085097 |
July2010–Dec2012 | Phase II clinical trial in SLE with active lupus nephritis (N = 47) | -62.5% of patients with active lupus nephritis received 0.5mg/day of laquinimod achieved renal response, compared to 33.3% of patients with placebo at 24 weeks | -Larger trial is needed to confirm result | https://www.tevapharm.com/ | |
| Metformin (AMPK activator) | Renji Hospital/ NCT02741960 |
May2016–Dec2018 | Proof of concept trial of add-on metformin to conventional immunosuppressants in lupus flares in SLE patients (N = 113) | -Metformin as an add-on can reduce clinical flares, prednisone exposure, and body weight | -Promising choice, larger trial is needed to confirm result | [171] |
hCDR1, human complementarity determining region 1; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000; AMS, Adjusted Mean Systemic Lupus Erythematosus Disease Activity Index-2K; BILAG, British Isles Lupus Assessment Group; CTLA4-Ig, cytotoxic T-lymphocyte–associated antigen 4-human Fc chimera; NIAID, National Institute of Allergy and Infectious Diseases; CD40L, CD40 ligand; NIAMS, National Institute of Arthritis and Musculoskeletal and Skin Diseases; BCDA-2, blood dendritic cell antigen-2; PK, Pharmacokinetics; IFN, interferon; CLE, cutaneous lupus erythematosus; PPARγ, peroxisome proliferator-activated receptor gamma; AhR, aryl hydrocarbon receptor; AMPK, selective AMP-activated protein kinase.