Table 3.

Key studies for amyloidosis pharmacotherapies.

Reference	Title	Type	Intervention	Control	Population	N	Primary endpoint	Results/status
Melphalan & bortezomib
NCT01277016	EMN-03	Phase 3 RCT	Bortezomib + melphalan + dexamethasone	Melphalan + dexamethasone	Treatment-naive AL amyloidosis	110	Number of patients with complete or partial response	Completed
Other proteasome inhibitors
NCT01659658	TOURMALINE-AL1	Phase 3 open label	Ixazomib + dexamethasone	Physician’s choice of oral chemotherapy	Relapsed or refractory AL amyloidosis with renal or cardiac involvement	248	Percentage of participants with overall hematologic response and 2-year vital organ deterioration and mortality rate	Recruiting
NCT01789242	A safety study of carfilzomib in patients with previously-treated systemic light chain amyloidosis	Phase 1	Carfilzomib + dexamethasone	N/A	Relapsed or refractory AL amyloidosis	32	Adverse events as measures of safety and tolerability	Ongoing
Anti-CD38 monoclonal antibody
NCT02841033	Daratumumab for the treatment of patients with AL amyloidosis	Phase 1/2	Daratumumab	N/A	Relapsed or refractory AL amyloidosis	25	Frequency and severity of side effects and number of patients with a treatment response	Recruiting
Immunomodulators
NCT01570387	A Phase I/II trial of pomalidomide and dexamethasone in subjects with previously-treated AL amyloidosis	Phase 1/2	Pomalidomide + dexamethasone	N/A	Previously treated AL amyloidosis	27	Dose-limiting toxicity and maximum tolerated dose	Pomalidomide is well tolerated in patients with AL amyloidosis and combined with dexamethasone has a hematologic response rate of 50% in previously treated patients.
NEOD001
NCT01707264		Phase 1/2	NEOD001	N/A	Previously treated AL amyloidosis with persistent organ dysfunction	69	Safety and tolerability	Treatment was safe and well tolerated with favorable organ responses compared with historical cohorts.
NCT02312206	VITAL	Phase 3 RCT	NEOD001	Placebo	Treatment-naive cardiac AL amyloidosis	236	Time to composite of all-cause mortality or cardiac hospitalization	Recruiting
NCT02632786	PRONTO	Phase 2 RCT	NEOD001	Placebo	AL amyloidosis with hematologic response and persistent cardiac dysfunction	100	Best cardiac response as measured by NT-proBNP at 1 year	Ongoing
Monoclonal anti-serum amyloid P antibody
NCT01777243		Phase 1	GSK2135698 + GSK2398852	N/A	Systemic amyloidosis involving spleen or liver	15	Safety as assessed by number of subjects with adverse events	Treatment led to clearance of amyloid deposits from the liver and other organs. No serious adverse events were observed.
NCT03044353	Multiple treatment session study to assess GSK2398852 administered following and along with GSK2315698	Phase 2 open label	GSK2135698 + GSK2398852	N/A	ATTR cardiomyopathy, AL cardiac amyloidosis in remission. or newly diagnosed AL amyloidosis with hematologic response	50	Change in left ventricular mass by cardiac magnetic resonance at 8-week follow up	Not yet recruiting
Tafamidis
NCT00694161		Phase 2 open label	Tafamidis 20 mg	N/A	V122I or wild-type ATTR cardiomyopathy	35	Percentage of patients with stabilized TTR tetramer at week 6	Tafamidis resulted in TTR stabilization in patients with ATTR cardiomyopathy.
NCT01994889	ATTR-ACT	Phase 3 RCT	Tafamidis 20 mg or tafamidis 80 mg	Placebo	ATTR cardiomyopathy	400	All-cause mortality and frequency of cardiovascular-related hospitalizations at month 30	Ongoing
Tolcapone
NCT02191826	Study of SOM0226 in familial amyloid polyneuropathy	Phase 1/2 open label	SOM0226 (tolcapone)	N/A	Familial ATTR polyneuropathy or asymptomatic carriers	17	TTR stabilization	Completed
RNA interference
NCT01617967		Phase 2 open label	Patisiran	N/A	Familial ATTR polyneuropathy	29	Safety and tolerability	Patisiran was well tolerated and effective in reducing both mutant and wild-type TTR levels
NCT01960348	APOLLO	Phase 3 RCT	Patisiran	Placebo	Familial ATTR polyneuropathy	225	Changed in modified Neuropathy Impairment Score	Ongoing
NCT02319005	ENDEAVOUR	Phase 3 RCT	Revusiran	Placebo	Familial ATTR cardiomyopathy	206	Change in 6 min walk distance at 18 months and percent reduction in serum TTR level over 18 months	Discontinued
Antisense oligonucleotides
NCT01737398	Efficacy and safety of IONIS-TTR Rx in familial amyloid polyneuropathy	Phase 3 RCT	IONIS-TTR Rx	Placebo	Familial ATTR polyneuropathy	172	The change from baseline in the modified Neuropathy Impairment Score and Norfolk Quality of Life Diabetic Neuropathy questionnaire at 65 weeks	Ongoing
NCT02175004		Phase 3 open label extension	IONIS-TTR Rx	N/A	Familial ATTR polyneuropathy enrolled in the phase 3 RCT	172	Adverse events during the 78 week treatment period	Ongoing
Doxycycline/tauroursodeoxycholic acid
NCT01171859	Safety, efficacy and pharmacokinetics of doxycycline plus tauroursodeoxycholic acid in transthyretin amyloidosis	Phase 2 open label	Tauroursodeoxycholic acid and doxycycline	N/A	ATTR amyloidosis	40	Changes in Neurologic Impairment Score-Lower Limbs and NTproBNP at 1 year	Completed
NCT01855360	Tolerability and efficacy of a combination of doxycycline and TUDCA in patients with transthyretin amyloid cardiomyopathy	Phase 1/2 open label	Tauroursodeoxycholic acid and doxycycline	N/A	ATTR cardiomyopathy	40	Change in longitudinal echocardiographic strain at 18 months	Ongoing
NCT02207556	Oral doxycycline administered as an adjunct to plasma cell directed therapy in light chain amyloidosis	Phase 2 open label	Doxycycline + chemotherapy	N/A	Treatment-naive AL amyloidosis	30	Amyloid organ response at 6 and 12 months	Recruiting
Green tea extract
NCT01511263	EpiCardiAL	Phase 2 open label randomized	EGCG + standard therapy	Standard therapy	Cardiac AL amyloidosis in remission	86	Cardiac response at 6 months	Recruiting
NCT02015312	TAME-AL	Phase 2 RCT	EGCG	Placebo	Cardiac AL amyloidosis in remission	38	Change in LV mass measured by cardiac MRI at 1 year	Ongoing