Table 2.

Completed or ongoing trials with Treg in autoimmunity and transplantation.

Study ID	Phase	Cell product	Indication	Dosing scheme	Tregs per dose	Outcome	Center	References
HSCT
NKEBN/458-310/2008	I	Expanded polytTregs	GvHD treatment	Single injection or3 injections	1 × 105/kg bw 3 × 106cells/kg bw	-Safe -Reduced immunosuppression in chronic GVHD -Only transient improvement in acute GVHD	Gdansk/PL	(88)
NCT00602693	I	Expanded CB polytTregs	GvHD prophylaxis	Single injection	Dose-escalation: 1, 3, 10, 30, 30+30, 100, 300, 1,000 and 3,000 × 105/kg bw	-Safe -Increased incidence of infections -Reduced incidence of acute GvHD/GvL effect	Minnesota/USA	(89, 90)
01/08	I	Fresh polytTregs	GvHD prophylaxis	Single injection	Dose-escalation: 0.5 × 106 Tcons/kg bw with 2 × 106 Tregs/kg bw 1 × 106 Tcons/kg bw with 2 × 106/Tregs kg bw −2 × 106 Tcons/kg bw with 4 × 106 Tregs/kg bw	-Safe -Reduced number of leukemia relapses -Reduced incidence of GVHD	Perugia/IT	(91, 92)
Treg002 EudraCT: 2012-002685-12	I	Fresh polytTregs	GvHD prophylaxis	Single injection	up to 5 × 106/kg bw	Safe	Regensburg/DE	(93)
EK 206082008	I	Expanded polytTregs	GvHD treatment	Single or 2 injections	0.97–4.45 × 106/kg bw	-Two cases of tumors -Stable chronic GvHD	Dresden/DE	(94)
ALT-TEN	I	Tr1 (IL-10 DLI or DC-10 DLI)	GvHD prophylaxis	Single injection	Dose-escalation: 1 × 105, 3 × 105 and 1 × 106, 3 × 106 CD3+ T cells/kg bw	-Safe -Long-term free-disease survival in 4 patients	Milan/IT	(95)
NCT02749084	I/II	Multiple Treg DLI	Severe Refractory Chronic GvHD prophylaxis	3 injections	Dose-escalation: 1.7 × 105, 3.3 × 105 and 6.6 × 105/kg bw per injection	Recruiting	Bologna/IT
NCT02991898	II	Fresh CB polyTregs with IL-2	aGvHD prophylaxis after CB Tx	Single injection	No data	Suspended	Minnesota/USA
NCT01911039	I	polyTregs	Steroid Dependent/ Refractory Chronic GvHD treatment	Single injection	Dose-escalation: 1 × 105, 5 × 105, 1.5 × 106 /kg bw	Unknown	Stanford/USA
NCT02385019	I/II	Fresh donor polyTregs	Steroid-Refractory Chronic GvHD treatment	Single injection	Dose-escalation: 0.5 × 106, 1.0 × 106 and 2.0–3.0 × 106/kg bw	Recruiting	Lisboa/PT
NCT01937468	I	Fresh polyTregs with IL-2	Steroid -Refractory Chronic GvHD treatment	Unknown	Unknown	Active/not recruiting	Boston/USA
NCT01903473	I	Fresh polyTregs with rapamycin	aGvHD and cGvHD treatment	Single injection	≥ 0.5 × 106/kg bw	Unknown	Liege/BE
EudraCT: 2012-000301-71	I	Fresh polyTregs with rapamycin	Steroid -Refractory Chronic GvHD treatment	Single injection	≥ 0.5 × 106/kg bw	Recruiting	Liege/BE
NCT01795573	I	Donor polyTregs expanded with recipient DC	aGvHD prophylaxis	Unknown	Unknown	Recruiting	Tampa/USA
NCT01660607	I/II	Fresh polyTregs with Tconv	aGvHD prophylaxis	Single injection	initial doses will be 1 × 106 Treg/kg bw to 3 × 106 Tcon/kg bw (ratio 1:3)	Recruiting	Stanford/USA
NCT02423915	I	Fucosylated fresh CB polyTregs	GvHD prophylaxis	Single injection	Dose-escalation: 1 × 106/kg bw 1 × 107/kg bw	Active/Not Recruiting	Houston/USA
BMT Protocol 204 NCT01050764	I	Fresh allogeneic polyTregs with Tconv	GvHD prophylaxis	Single injection	Dose-escalation: 1 × 105 Treg and 3 × 105 T con/kg bw or 3 × 105 Treg and 1 × 106 Tcon/kg bw or 1 × 106 Treg and 3 × 106 Tcon kg/bw or 3 × 106 Treg and 1 × 107 Tcon/kg bw	Terminated, GvHD was within parameters to continue, but the study was terminated due to poor outcomes prior to sufficient accrual to set the MTD, even at the only dose tested (1 × 105 Treg and 3 × 105 T con/kg bw). Primary outcome result is null.	Stanford/USA
NCT01634217	I	iTregs	GvHD prophylaxis	Unknown	Unknown	Active, not recruiting	Minnesota/USA
TRANSPLANTATION
NCT02129881	I/II	Expanded polytTregs	Living donor kidney Tx	Single injection	1–10 × 106 /kg bw	Completed, no results yet	London, Oxford/UK	(20)
ONEnTreg13 NCT02371434 EudraCT: 2013-001294-24	I/II	Expanded polytTregs	Living donor kidney Tx	Single injection	Dose-escalation: 0.5 × 106, 1 × 106, and 3 × 106/kg bw	Completed, no results yet	Berlin/DE	(20)
DART NCT02244801	I/II	Donor-Alloantigen-Reactive (dar) Tregs	Living donor kidney Tx	Single injection	Dose-escalation: 300 × 106 darTreg or 900 × 106darTreg	No longer recruiting	San Francisco/USA	(20)
NCT02091232	I/II	Belatacept-conditioned Tregs	Living donor kidney Tx	Unknown	Unknown	No longer recruiting	Boston/USA	(20)
ThRIL NCT02166177	I	Expanded polytTregs	Liver Tx	Single injection	low dose and high dose	Completed, no results yet	London/UK
NCT02188719	I	Donor-Alloantigen-Reactive Tregs	Liver Tx	Single injection	Dose-escalation: 0 × 106 darTreg or 50 × 106 darTreg or 200 × 106 darTreg or 800 × 106 darTreg	Recruiting	San Francisco/USA
NCT02088931	I	Expanded polytTregs	Subclinical rejection in kidney Tx	Single injection	200 × 106	Open/Not recruiting	San Francisco/USA
NCT02474199	I	Donor-Alloantigen-Reactive Tregs	CNI reduction in liver Tx	Single injection	300–500 × 106 /kg bw	Recruiting	San Francisco/USA
NCT01624077	I	Donor-antigen expanded Tregs	Liver Tx	Multiple injections at several intervals	1 × 106 /kg bw per injection	Unknown	Nanjing/CHN
NCT01446484	I	polytTregs	Living donor kidney Tx	Single injection sub-cuntaneous	2 × 108 s.c.	Unknown	Moscow/RUS
TRACT NCT02145325	I	Expanded polytTregs	Living donor kidney Tx	Unknown	Unknown	Active, Not recruiting	Chicago/USA
NCT02711826	I/II	Donor-Alloantigen-Reactive Tregs vs. polytTregs	Subclinical rejection in kidney Tx	Single injection	400 ± 100 × 106 darTregs	Recruiting	Birmingham, Los Angeles, San Francisco, Ann Arbor, Cleveland/USA
AUTOIMMUNITY
TregVAC ISRCTN06128462	I	Expanded polytTregs	Recent T1D	Single or 2 injections	Dose-escalation: 10 × 106, 20 × 106, or 30 × 106/kg bw	-Completed -Safe -Reduced insulin consumption (insulin independence in 2 out of 12 patients) -Better stimulated C-peptide secretion profiles	Gdansk/PL	(96–98)
NCT01210664	I	Expanded polytTregs	T1D	Single injection	Dose-escalation: 0.05 × 108, 0.4 × 108, 3.2 × 108, 26 × 108	Completed/Safe	San Francisco/USA	(99)
CATS1	I/II	Ovalbumin-specific Tr1	Refractory Crohn's disease	Single injection	Dose-escalation: 1 × 106, 107, 108, or 109	-Safe -Clinical response in 40% of patients	Lille/FR	(100)
CATS29 EudraCT: 2014-001295-65 NCT02327221	II	Ovalbumin-specific Tr1	Refractory Crohn's disease	Single injection	1 × 106/kg bw	Terminated/completed	Valbonne/FR Multicenter: AT, BE, FR, GE, IT, UK
TregVAC2.0 EudraCT: 2014-004319-35	II	Expanded polytTregs combined with antiCD20 antibody	Recent T1D	2 injections, 3 months apart	30 × 10/kg bw per injection	Recruitment closed/Follow up in progress	Gdansk/PL
TregSM EudraCT: 2014-004320-22	I	Expanded polytTregs	MS	Single injection: Cohort I – intravenous Cohort II - intrathecal	Up to 40 × 106/kg bw	Recruiting	Gdansk/PL
NCT02704338	I	Expanded polytTregs	Autoimmune hepatitis	Single injection	10-20 × 106/kg bw	Not yet recruiting	Nanjing/CHN
NCT02772679	II	Expanded polytTregs with IL2	Recent T1D	Single injection	3 or 20 × 106/kg bw	Suspended	San Francisco/USA
NCT02428309	II	Expanded polytTregs	Systemic lupus erythematosus	Single injection	Dose-escalation: 1 × 108 or 4 × 108 or 16 × 108	Active/Not Recruiting	San Francisco/USA
NCT02932826	I	Expanded third-party CB polyTregs	Recent T1D	Single injection	1–5 × 106/kg bw	Recruiting	Hunan/CHN
NCT03011021	I	Expanded third-party CB polyTregs and Liraglutide	Recent T1D	Single injection	1–5 × 106/kg bw	Recruiting	Hunan/CHN
T-Rex Study NCT02691247	II	Expanded polytTregs	Recent T1D	Single injection	low dose and high dose	Active/Not Recruiting	San Francisco, Aurora, New Haven, Gainesville, Miami, Indianapolis, Boston, Fargo, Kansas City, Portland, Sioux Falls, Nashville/USA
OTHER
NCT03101423	I	Donor polyTregs DLI	Beta Thalassemia Major	Unknown	Unknown	Active/Not Recruiting	Nanning/CHN
NCT03241784	I	Donor polyTregs DLI	Amyotrophic Lateral Sclerosis (ALS)	8 injections iv in total concomitant with IL2 sc.: 4 injections over 2 months at early stage and 4 injections over 4 months at later stages	1 × 106/kg bw per injection	completed	Houston/USA	(101)

This table is an updated version of the table in (102) and is based on information deposited on www.clinicaltrials.gov, www.clinicaltrialsregister.eu and/or indicated references. Route of administration of the Tregs is intravenous, except where otherwise noted. AE, adverse event; T1D, type 1 diabetes; Tx, transplantation; MS, multiple sclerosis; /kg bw, per kg body weight; HSCT, hematopoetic stem cell transplantation; CB, cord blood; GvHD, graft vs. host disease.