Table 1.

Nanobodies that have entered in clinical trials

Nanobody drug	Disease	Target	Clinical trial	Phase of clinical development	References
Caplacizumab ALX-0681 ALX-0081	Thrombotic thrombocytopenic purpura	Ultra large von Willebrand factor	NCT03172208 NCT02878603 NCT01151423 NCT02189733 NCT02553317 NCT01020383	I III II I III II	[98, 139–143]
Ozoralizumab ATN-103	Rheumatoid arthritis	TNF	NCT01007175 NCT00959036 NCT01063803 NCT00916110	I/II I/II II I	[144]
Vobarilizumab ALX-0061	Rheumatoid arthritis	IL6	NCT02518620 NCT02309359 NCT02287922 NCT02101073 NCT01284569	II II II I I/II	[145]
Vobarilizumab ALX-0061	Systemic lupus erythematosus	IL6	NCT02437890	II
ALX-0171	Lower respiratory tract infection	RSV	NCT02979431 NCT02309320 NCT01483911 NCT01909843 NCT01875926 NCT03468829 NCT03418571	II I/II I I I II II	[114, 146]
ALX-0761 M1095 MSB0010841	Psoriasis	IL17A, IL17F and IL17A/F	NCT03384745 NCT02156466	II I	[147]
Bispecific nanobody-derived CAR-T cells	Refractory/ relapsed B-cell lymphoma	CD19/CD20	NCT03881761 NCT03664661	I I	[105, 148]
α-ADAMTS-5 nanobody M6495	Osteoarthritis	ADAMTS-5	NCT03583346 NCT03224702	I I	[149, 150]
VHH batch 203027	Diarrhoea	Rotavirus	NCT01259765	II	[151]
[131I]-SGMIB anti-HER2 VHH1	Breast cancer	HER2	NCT02683083	I
68-GaNOTA-anti-HER2 VHH1	Brain metastasis of breast carcinoma	HER2	NCT03331601	II
ALX-0651	Healthy volunteers	CXCR4	NCT01374503	I
PF-05230905	Healthy volunteers		NCT01284036	I

Phase I: dosing, toxicity and excretion in healthy subjects; Phase II: safety and efficacy in large patient cohorts; Phase III: multi-centred, randomized, placebo-controlled trials; Phase IV: post-marketing studies

ADAMTS-5 α-A disintegrin and metalloproteinase with thrombospondin motifs-5, CAR chimeric antigen receptor, CD cluster of differentiation, CXCR4 chemokine receptor type 4, HER2 human epidermal growth factor receptor 2, IL interleukin, RSV respiratory syncytial virus, TNF tumour necrosis factor