Table 2.

Targeted therapy strategies being investigated in KOA clinical trials.

Targeted therapy strategies	Type of drug/carrier	Drug name	Administration routes	Safety and	Effectiveness	Clinicaltrials.gov identifier	Current phase of development	References of clinical data
Small-molecule inhibitors	ADAMTS5 inhibitor	GLPG1972/S201086	Oral	Well-tolerated	Inefficacy	NCT03311009, NCT03595618	Phase II	[54–56]
	Cathepsin K inhibitor	MIV-711	Oral	Well-tolerated	Significant reduction of the progression of bone area and cartilage thinning	NCT02705625	Phase II	[60]
	Wnt signaling inhibitors	Lorecivivint	Intra-articular	Well-tolerated	Pain reduction and enhanced joint function	NCT02536833, NCT03122860, NCT04385303, NCT03928184, NCT05603754	Phase III	[65–68]
Monoclonal antibodies	Neutralizing antibody against ADAMTS5	M6495	Subcutaneous	Well-tolerated	Effective inhibition of aggrecan degradation	NCT03583346	Phase II	/
	Neutralizing antibody against NGF	Tanezumab, Fasinumab	Subcutaneous	The potential for joint-related adverse events	Significant pain relief	NCT03304379, NCT02528188	Phase III	[82]
	Anti-CCL17 antibody	GSK3858279	Intravenous, subcutaneous	Favorable safety and tolerability	Significant improvements in knee pain	NCT03485365	Phase I	/
Nanocarrier-based therapy	Liposomes	Bupivacaine	Intra-articular	Good safety	The prolonged analgesia	NCT04910165	Phase III	[112]
	Liposomes	Dexamethasone	Intra-articular	Minimization of systemic exposure and associated risks	The prolonged pain relief and improved joint function	NCT04123561	Phase III	/
Gene therapy	Chondrocytes	Tissuegene-C	Intra-articular	Well-tolerated	Increase of cartilage thickness and slower rates of subchondral bone surface area growth	NCT02072070	Phase III	[113]
	Nonviral gene therapy	XT-150	Intra-articular	Well-tolerated	Significant improvements in pain and function	NCT04124042	Phase II	/
	Adeno-associated viral vectors	Sc-raav2.5IL-1Ra	Intra-articular	–	–	NCT02790723	Phase I	/
	Adeno-associated viral vectors	GNSC-001	Intra-articular	–	–	NCT05835895	Phase I	/
	Adeno-associated viral vectors	FX201	Intra-articular	–	–	NCT04119687	Phase I	/
Cytotherapy	Mesenchymal stem cells	AT-mscs	Intra-articular	Joint-related adverse events	Limited pain relief and functional improvement	NCT01183728, NCT03869229, NCT05081921, NCT05783154	Phase II	[114–117]
	MSC-exos	Exooa-1	Intra-articular	–	–	NCT05060107	Phase I	/

ADAMTS = a disintegrin and metalloproteinase with thrombospondin motifs, KOA = knee osteoarthritis, MSC-Exos = mesenchymal stem cell-derived exosomes.

“–” represents no results posted; “/” represents no reference available.