Table 2.

Pharmacological clinical trials registered at the World Health Organization (WHO) International Clinical Trials Research Platform (ICTRP) for people with Huntington’s disease (HD) since the first edition of the “Huntington’s Disease Clinical Trials Corner”. N/S, not specified; PD, Parkinson’s disease; VMAT2, Vesicular Monoamine Transporter 2. Note: IONIS-HTT_Rx, ISIS 443139, RG6042 and tominersen refer to the same molecule. New trials added since the last Clinical Trials Corner are indicated by*

Registration ID	Trial name	Intervention	Mechanism of Action	Population	Comparison	Main outcome	Study design	Estimated Enrolment	Sponsor	Location
NCT04556656*	PROOF-HD	Pridopidine	Sigma-1 receptor activation	Early HD	Placebo	Change in function at 65 weeks	Randomized, double-blind, parallel assignment, single dose trial	499	Prilenia therapeutics	Austria, Canada, Czechia, France, Germany, Italy, Netherlands, Poland, Spain, United Kingdom, United States
NCT05686551*	GENERATION HD2	Tominersen	Non allele selective antisense oligonucleotide	Prodromal and early manifest HD	Placebo	Safety at 24 months	Randomized, double-blind, dose-finding trial	360	Hoffmann-La Roche	United States, Spain, more sites to be condirmed
NCT05655520*	–	SAGE-718	Positive allosteric modulator of NMDA	PreHD, early and moderate HD	None	Safety at 13 months	Single-dose open label trial	300	Sage Therapeutics	United States
NCT03019289*	–	Pridopidine	Sigma-1 receptor activation	Healthy controls, early and moderate HD	None	Sigma-1 receptor occupancy	Multiple dose, open label trial	23	Prilenia therapeutics / Teva	Germany
NCT02494778*	Open PRIDE HD	Pridopidine	Sigma-1 receptor activation	Early and moderate HD	Placebo	Efficacy at 106 weeks	Open-label extension	400	Prilenia therapeutics / Teva	Australia, Austria, Canada, France, Germany, Italy, Netherlands, Poland, Russia, United Kingdom, United States
NCT02006472*	PRIDE HD	Pridopidine	Sigma-1 receptor activation	Early and moderate HD	Placebo	Efficacy at 26 weeks	Randomized, double-blind, parallel assignment, dose-finding trial	408	Prilenia therapeutics / Teva	Australia, Austria, Canada, Denmark, France, Germany, Italy, Poland, Russia, Netherlands, United Kingdom, United States
NCT01306929*	OPEN-HART	Pridopidine	Sigma-1 receptor activation	HD	None	Safety up to 72 months	Randomized, placebo-controlled, dose-ranging, parallel-group study.	134	Prilenia therapeutics / Teva	Canada, Inited States
NCT05509153	–	N-Acetyl Cysteine	Antioxidant	Premanifest HD	Placebo	Efficacy at 36 months	Randomized, double-blind trial	160	Western Sydney Local Health District	Australia
ISRCTN56240656	FELL-HD	Felodipine	Calcium channel blocker	Early HD	None	Safety at 62 weeks	Non-randomised, multiple dose trial	18	Cambridge University	United Kingdom
NCT05358821	–	SAGE-718	Positive allosteric modulator of NMDA	Early and moderate HD	Placebo	Change in cognition at 28 days	Double-blind, placebo-controlled, single dose design trial	80	Sage Therapeutics	United States
NCT05358717	PIVOT HD	PTC518	Small molecule splicing modulator	PreHD, prodromal and early HD	Placebo	Safety at 113 days	Randomized, double-blind, placebo controlled, parallel assignment, multiple dose trial	162	PTC therapeutics	France, Germany, Netherlands, United Kingdom, United States
NCT05475483	–	SOM-3355 (bevantolol hydrochloride)	Beta-blocker	Early and moderate HD	Placebo	Efficacy at 8 weeks	Randomized, double-blind, placebo-controlled, parallel assignment multiple-dose trial	129	SOM Biotech	France, Germany, Italy, Poland, Spain, Switzerland, United Kingdom
ACTRN12621001755820	–	SLS-005 (Trehalose)	Disaccharide	Early HD, ALS, SCA3	None	Efficacy at 24 weeks	Non-randomized, open-label	15-18 (4 ALS, 10 HD, 4 SCA3)	Seelos Therapeutics	Australia
NCT05541627	–	AB-1001 (BV-101)	AAV encoding for CYP46A1, enzyme converting cholesterol to 24-OH-cholesterol	Early HD	None	Safety at week 52	Non-randomized, open-label, sequential, single ascending dose	18	AskBio/ BrainVectis	France
NCT05107128	DIMENSION	SAGE-718	Positive allosteric modulator of NMDA	Early and moderate HD	Placebo	Change in cognition at 85 days	Double-blind, placebo-controlled, single dose design	178	Sage Therapeutics	Australia, Canada, United States
NCT05111249	VIBRANT HD	Branaplam	Small molecule splicing modulator	Early HD	Placebo	Reduction of mHTT protein at week 17Safety at 104 weeks	Double-blind, placebo-controlled multiple dose design	75	Novartis Pharmaceuticals	Belgium, Canada, France, Germany, Hungary, Italy, Spain, United Kingdom, United States
NCT05032196	SELECT-HD	WVE-003	Allele-selective antisense oligonucleotide	Early HD	Placebo	Safety at 36 weeks	Randomized, double-blind, placebo-controlled, combined single ascending dose/multiple ascending dose trial	36	Wave Life Sciences Ltd.	Australia, Canada, Denmark, France, Germany, Poland, Spain and United Kingdom
NCT05243017	–	AMT-130	rAAV5-miHTT	Early HD	None	Safety at 6 months	Non-randomized, sequential ascending, multiple-dose trial	15	UniQure Biopharma B.V.	Germany, Poland, United Kingdom
NCT04713982	–	Deutetra-benazine	VMAT2 inhibitor	HD with chorea	None	Change in speech outcome at 10 weeks	Single-arm open label trial	30	Vanderbilt University Medical Center	USA (single centre)
NCT04826692	–	Metformin	Antihyper-glycemic/ AMPK activator	Early and moderate HD	Placebo	Change in cognition at 52 weeks	Randomized, parallel assignment, double-blinded trial	60	Instituto de Investigacion Sanitaria La Fe	Spain (single centre)
NCT04514367	–	ANX005	C1q inhibitor	Early HD	None	Safety at 36 weeks	Single-dose open label trial	28	Annexon, Inc	USA (multi-centre)
NCT04421339	–	Melatonin	Melatonin receptor agonist	HD with sleep disturbance	Placebo	Sleep quality at 9 weeks	Randomised, cross-over, single-blinded (participant/caregiver)	20	The University of Texas Health Science Center, Houston	USA (single centre)
NCT04400331	–	Valbenazine	VMAT2 inhibitor	Early and moderate HD	None	Safety at 104 weeks	Open label, single arm trial	150	Neurocrine Biosciences	USA and Canada
NCT04301726	–	Deutetra-benazine	VMAT2 inhibitor	HD with dysphagia	Placebo	Dysphagia at 18 months	Randomized, parallel assignment, triple blinded trial	48	Fundacion Huntington Puerto Rico	N/S
NCT04478734	HUNTIAM	Thiamine and biotin	B vitamins	HD	Moderate vs High doses of thiamine and biotin	Safety at 52 weeks	Randomized, parallel assignment, open-label trial	24	Fundación Pública Andaluza para la gestión de la Investigación en Sevilla	Spain (single centre)
NCT04201834	–	Risperidone	Dopamine antagonist	Early and moderate HD with chorea	None	Change in motor scales at 12 weeks	Non-randomized, open label (assessor-blind), uncontrolled trial	12	University of Rochester	USA (single centre)
NCT04071639	–	Haloperidol, risperidone, sertraline and coenzyme Q10	Multiple (dopamine antagonists, selective serotonin reuptake inhibitor, dietary supplement)	Early and moderate HD	Coenzyme Q10	Efficacy at 5 years	Randomized, open label, controlled, parallel trial	100	Second Affiliated Hospital, School of Medicine, Zhejiang University	China (single centre)
NCT04120493	AMT-130	rAAV5-miHTT	Non allele selective miRNA	Early HD	Sham intervention	Safety at 18 months	Randomized, double-blind, sham-controlled, parallel trial	26	UniQure Biopharma B.V.	USA (multi-centre)
NCT04102579	KINECT-HD	Valbenazine	VMAT2 inhibitor	HD with chorea	Placebo	Efficacy at 12 weeks	Randomized, double-blind, placebo-controlled, parallel trial	120	Neurocrine Biosciences, Huntington Study Group	USA (multi-centre)
EUCTR2019-002178-30-DK	–	WVE-120102	Allele-selective antisense oligonucleotide	HD	None	Safety and tolerability at 97 weeks	Open-label extension	70	Wave Life Sciences Ltd.	Australia, Canada, Denmark, France, Poland and United Kingdom (multi-centre)
NCT04000594	GEN-PEAK	RG6042	Allele-nonselective antisense oligonucleotide	HD	None	Pharmaco-dynamics and pharmacokinetics at multiple timepoints until 6 months	Non-randomized. open-label, multiple-dose, parallel trial	20	Hoffmann-La Roche	The Netherlands and UK (multi-centre)
NCT03980938	–	Neflamapimod	p38α MAPK inhibitor	Early HD	Placebo	Change in cognitive scales at 10 weeks	Randomized, double-blind, placebo-controlled, cross-over trial	16	EIP Pharma Inc, Voisin Consulting, Inc.	UK (single centre)
NCT03842969	GEN-EXTEND	RG6042	Allele-nonselective antisense oligonucleotide	HD	None	Safety and tolerability at up to 5 years	Open-label extension	1050	Hoffmann-La Roche	USA, Canada, Europe (multi-centre)
NCT03761849	GENERATION-HD1	RG6042	Allele-nonselective antisense oligonucleotide	HD	Placebo	Clinical efficacy at 101 weeks	Randomized, double-blind, placebo-controlled, parallel trial	909	Hoffmann-La Roche	USA, Canada, Europe (multi-centre)
NCT03515213	–	Fenofibrate	PPARα agonist	HD	Placebo	Pharmaco-dynamics at 6 months	Randomized, double-blind, placebo-controlled, parallel trial	20	University of California, Irvine	USA (single centre)
NCT03764215	Tasigna HD	Nilotinib	Selective Bcr-Abl tyrosine kinase inihbitor	HD	None	Safety, tolerability and pharmacodynamics at 3 months	Open label, multiple ascending dose	20	Georgetown University	USA (single centre)
NCT03225833	PRECISION-HD1	WVE-120101	Allele-selective antisense oligonucleotide	HD	Placebo	Safety and tolerability at 1 and 120 days	Randomized, double-blind, placebo-controlled, combined single ascending dose/multiple ascending dose trial	48	Wave Life Sciences Ltd.	Australia, Canada, Denmark, France, Poland and United Kingdom (multi-centre)
NCT03225846	PRECISION-HD2	WVE-120102	Allele-selective antisense oligonucleotide	HD	Placebo	Safety and tolerability at 1 and 120 days	Randomized, double-blind, placebo-controlled, combined single ascending dose/multiple ascending dose trial	60	Wave Life Sciences Ltd.	Australia, Canada, Denmark, France, Poland and United Kingdom (multi-centre)
NCT02453061	TRIHEP 3	Triheptanoin	Anaplerotic therapy	HD	Safflower oil	Pharmaco-dynamic efficacy at 6 months	Randomized, double-blind, controlled, parallel trial	100	Institut National de la Sant $\acute{\mathrm{e}}$ Et de la Recherche M $\acute{\mathrm{e}}$ dicale, Ultragenyx Pharmaceutical Inc	France, Netherlands (multi-centre)
NCT02509793	–	Tetrabenazine	VMAT2 inhibitor	HD with impulsivity	None	Cognitive and behavioural effects at 8 weeks	Single group, open-label trial	20	University of Texas Health Science Center, and H. Lundbeck A/S	USA (single centre)
NCT02481674	SIGNAL	VX15/2503	Anti-semaphorin 4D monoclonal antibody	Late premanifest or early HD	Placebo	Safety and tolerability at 15 and 21 months	Randomized, double-blind, placebo-controlled, parallel trial	240	Vaccinex Inc., Huntington Study Group	USA (multi-centre)
EUCTR2013-002545-10-SE	OSU6162Open1309	(-)-OSU616	Monoaminergic stabilizer	HD, PD, brain trauma, stroke, myalgic encephalomyelitis and narcolepsy	None	Safety at 3, 6 and 12 months	Single group, open-label trial	240	A. Carlsson Research AB	Sweden (multi-centre)
NCT00514774	UDCA-HD	Ursodiol	Bile acid	HD	Placebo	Safety, tolerability and pharmacokinetics at 35 days	Randomized, double-blind, placebo-controlled, parallel trial	21	Oregon Health and Science University, Huntington Study Group, Huntington Society of Canada	N/S