Table 1.

Add-On Clinical Trials of Combination Treatments for AD

Agent	Dose	Type	AD Stage	Phase	Baseline Therapy*	Clinical Trials
Disease modifying
Aducanumab	NR	Amyloid passive immunization	Early	III	SOC†	NCT02484547
						NCT02477800
Gantenerumab	NR		Early	II/III	NR‡	NCT01760005
				III	SOC†	NCT02051608
Crenezumab	NR	Amyloid passive immunization	Early	III	SOC†	NCT02670083 NCT03114657
Solanezumab	NR	Amyloid passive immunization	Early	II/III	NR‡	NCT01760005
JNJ-54861911	NR	BACE inhibitor	Early	II/III	NR‡	NCT01760005
Masitinib	3.0 or 4.5 mg/kg/d	Selective tyrosine kinase inhibitor	Mild to moderate	III	Rivastigmine and/or memantine	NCT01872598
ALZT-OP1 (cromolyn and ibuprofen)	NR	Anti-amyloid/anti-inflammatory	Early	III	AChEI’s† and/or memantine†	NCT02547818
Flebogama DIF 5% and Albutein 20%	NR	Intravenous human immunoglobulin, human albumin	Mild, moderate	II/III	AChEI’s and/or memantine	NCT01561053
BAN2401	2.5, 5.0, or 10.0 mg/kg once biweekly; or 5.0 or 10 mg/kg once a month	Amyloid passive immunization	Early	II	AChEI’s† and/or memantine†	NCT01767311
AADvac-1	Axon peptide 108 40 μg; 6 doses in 4-week intervals, then 5 doses in 3-month intervals	Tau active immunization	Mild	II	AChEI; memantine (permitted but not required	NCT02579252
ABBV-8E12	NR	Tau passive immunization	Early	II	SOC†	NCT02880956
Nasal insulin	Insulin 20 IU BID	Peptide hormone	Early	II/III	NR‡	NCT01767909
	Glulisine 20 IU BID			II	AChEI or memantine	NCT02503501
Liraglutide	1.8 mg/d	GLP-1 receptor agonist	Mild	II	AChEI†	NCT01843075
Sargramostim	250 μg/m2/d for 5 days/week for 3 weeks	GM-CSF	Mild, moderate	II	AChEI† and/or memantine† or Axona†	NCT01409915
Telmisartan	40 or 80 mg/d	Angiotensin II receptor antagonist	Mild, moderate	II	AChEI and/or memantine	NCT02085265
Nicotinamide	1500 mg BID	Vitamin B3	Early	II	SOC†	NCT03061474
Saracatinib	100 to 125 mg/d	Src/abl kinase family inhibitor	Mild	II	AChEI’s† and/or memantine† and/or antidepressants†	NCT02167256
UE2343	10 mg/d	β-hydroxysteroid dehydrogenase inhibitor	Mild	II	AChEI’s† and/or memantine†	NCT02727699
ANAVEX2-73	30 or 50 mg/d	Sigma-1 chaperone agonist	Mild, moderate	II	SOC	NCT02244541 NCT02756858
BIIB092	NR	Tau passive immunization	Early	II	SOC†	NCT03352557
Curcumin and yoga	Curcumin: 800 mg/d; yoga: aerobic or nonaerobic	Dietary supplement/ exercise regimen	MCI	II	NR†	NCT01811381
Deep brain stimulation of the fornix	NR	Procedural intervention	NR	NA	AChEI’s and/or memantine	NCT03290274
Neflamapimod	40 mg BID	p38 MAPK alpha inhibitor	Early, mild	II	AChEI† or memantine†	NCT03402659
Repetitive transcranial magnetic stimulation	2 or 4 weeks of once-daily treatment 5 days/week; at 20Hz	Procedural intervention	Mild, moderate	NA	AChEI†	NCT02908815
CT1812	280 or 560 mg/d	Sigma-2 receptor ligand	Mild, moderate	I/II	AChEI† or memantine†	NCT02907567
T3D-959	3, 10, 30, or 90 mg/d for 2 weeks	PPARδ/γ agonist	Mild, moderate	I/II	NR‡	NCT02560753
ACI-24	340 to 460 μg/mL	Amyloid passive immunization	Mild, moderate	I/II	AChEI	2008-006257-40 (EudraCT)
ACI-35	NR	Tau active immunization	Mild, moderate	I	AChEI	ISRCTN13033912 (ISRCTN registry)
ABvac40	NR	Amyloid active immunization	Mild, moderate	II	NR†	Unregistered trial ongoing
TPI 287	2.0, 6.3, or 20 mg/m2 once every 3 weeks	Microtubule stabilizer	Mild, moderate	I	SOC†	NCT01966666
LY3303560	NR	Tau passive immunization	Early, mild, moderate		AChEI†, memantine,† and/or other AD therapy†	NCT03019536
					NR‡	NCT02754830
Idalopirdine	30 or 60 mg/d	5-HT6 antagonist	Mild, moderate	III	Donepezil 10 mg/d	NCT01955161
	10 or 30 mg/d				Donepezil 10 mg/d	NCT02006641
	30 or 60 mg/d				AChEI	NCT02006654
	60 mg/d				Donepezil 10 mg/d or donepezil 10 mg/d and memantine (IR 20 mg/d or XR 28 mg/d)	NCT02079246
Intepirdine	35 mg/d	5-HT6 antagonist	Mild, moderate	III	Donepezil 5 or 10 mg/d	NCT02585934
				II	AChEI	NCT02910102
LY3002813	NR; alone or in combination with LY3202626	Amyloid passive immunization	Early	II	AChEI and/or memantine	NCT03367403
Symptomatic
Levetiracetam	NR	Anticonvulsant	Mild, moderate	II	Donepezil,† galantamine,† rivastigmine,† or memantine†	NCT02002819
SUVN-502	NR	5-HT6 antagonist	Moderate	II	Donepezil and memantine	NCT02580305
Citalopram	30 mg/d	Selective serotonin reuptake inhibitor	Mild, moderate, severe	III	SOC	NCT00898807
Sertraline	25 to 125 mg/d (target dose, 100 mg/d)	Selective serotonin reuptake inhibitor	NR	II/III	SOC	NCT00086138
Risperidone	Up to 1.5 mg/d followed by divalproex if agitation persists	Serotonin-dopamine antagonist antipsychotic	NR	IV	NR‡	NCT00208819
Olanzapine	Up to 7.5 mg/d followed by divalproex if agitation persists	Multi-acting receptor-targeted antipsychotic	NR	IV	NR‡	NCT00208819
Quetiapine	NR	Multi-acting receptor-targeted antipsychotic	NR	NA	AChEI†	NCT00232570
Brexpiprazole	1 or 2 mg/d	Partial dopamine receptor agonist	Mild, moderate, severe	II/III	NR	NCT03620981
Aripiprazole	2, 3, or 6 mg/d	Partial dopamine receptor agonist	Mild, moderate, severe	III	NR‡	NCT02168920
Rasagiline	0.5 mg/d, uptitrated to 1 mg/d	Monoamine oxidase B inhibitor	Mild, moderate	II	AChEI† or memantine†	NCT02359552
Piromelatine	5, 20, or 50 mg/d	Melatonin and serotonin receptor agonist	Mild	II	Prescribed drugs for AD including AChEI’s†	NCT02615002
Riluzole	NR	Glutamate neurotransmission modulator	Mild	II	Donepezil or rivastigmine† or galantamine†	NCT01703117

5-HT, 5-hydroxytrytamine (serotonin); AChEI, acetylcholinesterase inhibitor; AD, Alzheimer’s disease; BACE, aspartyl protease β-site amyloid precursor protein cleaving enzyme 1; BID, twice-daily; EudraCT, European Clinical Trials Database; GLP-1, glucagon-like peptide-1; GM-CSF, granulocyte-macrophage colony-stimulating factor; IR, immediate release; MAPK, mitogen-activated protein kinase; MCI, mild cognitive impairment; NA, not available; NR, not reported; PPAR, peroxisome proliferator-activated receptor; SOC, standard-of-care medication(s) for AD (agent/dose not specified); XR, extended release. ^*Doses of baseline therapy were not reported except where indicated. ^†Patients who were receiving stable standard-of-care therapy and those not currently receiving therapy were eligible. ^‡Available inclusion/exclusion criteria did not note baseline use of AD therapy.