Skip to main content

Table 1 Clinical trials in recent 10 years

From: A perspective on therapies for amyotrophic lateral sclerosis: can disease progression be curbed?

Clinical trial identifier

Phase /subjects

Drug

Treatment

Duration

Primary outcome measure

Main findings

Oxidative stress

 NCT00330681/ [18]

Phase III

206 participants

Edaravone

(MCI-186)

Placebo (n = 104) or edaravone (n = 102) i.v. infusion over 60 min for the first 14 days in cycle 1, and for 10 of the first 14 days during cycles 2 to 6.

2006.05-2008.09

ALSFRS-R

Small reduction of ALSFRS-R scores was observed in the edaravone group.

 NCT01492686/ [19]

Phase III

137 participants

Edaravone

(MCI-186)

Placebo (n = 69) or edaravone (n = 68) i.v. infusion over 60 min for the first 14 days in cycle 1, and for 10 of the first 14 days during cycles 2 to 6.

2011.12–2014.9

ALSFRS-R

Edaravone improved ALSFRS-R scores in a small subset of people.

Autophagy

 UMIN000036295/ [20]

Phase I

Bosutinib

Three to six patients with ALS were enrolled at each of the four bosutinib dose levels (100, 200, 300 or 400 mg/day).

2019.03–2021.03

DLT

Undergoing.

 NCT02166944/ [21]

Phase I/II

20 participants

Tamoxifen

Tamoxifen 40 mg (n = 10) or riluzole (n = 8) daily for 1 year.

2014.04–2019.09

ALSFRS-R

Tamoxifen exerted only a modest effect in attenuating progression for 6 months.

Cell therapy

 NCT01640067/ [22]

Phase I

18 participants

HSSCs

Three received 3 unilateral injections of hNSCs into the lumbar cord tract, while the others received bilateral injections. A total of 750,000 cells per injection site (15 μ).

2011.12–2015.12

Treatment-related mortality, AEs, neuroradiological and neurophysiological variables

Transplantation of hNSCs was confirmed to be a safe cell therapy approach with good reproducibility.

Transient improvement in ALSFRS-R and MRC was observed in some patients.

 NCT01348451/ [23]

Phase I

18 participants

HSSCs

Ten microliters were delivered at a rate of 5 μl/min over 2 min by unilateral cervical injections, for a total of 500,000 cells (NSI-566RSC HSSC line) in the 5 injections.

2009.01–2016.12

AEs

Safety and feasibility of cervical and dual-targeting approaches (both lumbar and cervical injection) was demonstrated.

 NCT01730716/ [24]

Phase II

18 participants

HSSCs

Three participants in each group. The numbers of injection (site: C3-C5 or L2-L4 bilateral injections) ranged from 10 to 40, and the numbers of cells (HSSCs) injected ranged from 2 million to 16 million.

2013.05–2016.11

AEs

Intraspinal transplantation of HSSCs was safe at high doses (20 injections, 400,000 cells/injection), including successive lumbar and cervical injections.

 NCT01640067/ [25]

Phase I

18 participants

hNSCs

Participants were divided into 3 groups with monolateral or bilateral injections (C3-C5 or T8-T11) of a total of 750,000 cells (15 μ hNSCs) per injection.

2011.12–2015.12

Treatment-related mortality, AEs, neuroradiological and neurophysiological variables

Safety of hNSC transplantation was confirmed.

A transitory decrease in progression of ALSFRS-R was observed, starting within the first month after surgery and up to 4 months after transplantation.

 NCT01363401/ [26, 27]

Phase I/II

72 participants

BM- MSCs

Each participant received 2 intrathecal injections of autologous BM-MSCs (1 × 106 cells/kg) 26 days apart.

Control group (n = 31, riluzole 100 mg alone).

2011.02–2013.08

ALSFRS-R

Two repeated intrathecal injections were safe and feasible throughout the 12-month duration.

 NCT01051882/ [28]

Phase I/II

12 participants

NurOwn®

Six patients in each group received i.m. or i.t. injection of NurOwn®.

2011.06–2013.03

Safety evaluation and tolerability.

Safe and well-tolerated.

 NCT01777646/ [28]

Phase IIa

14 participants

NurOwn®

Fourteen patients received combined i.t. and i.m. delivery. (IM at 24 sites to the biceps and triceps (1 × 106 cells/site); i.t. of 1 × 106 cells/kg)

2012.12–2015.09

Safety evaluation and tolerability

Improvement in the decrease rate of progression of the FVC and ALSFRS-R was demonstrated in the i.t. (or i.t. + i.m.)–treated groups.

 NCT02017912/ [29]

Phase II

48 participants

MSC-NTF cells

MSC group (n = 36): MSC-NTF cells. Placebo (n = 12): Dulbecco Modified Eagle Medium.

Combination of i.t. (125 × 106 cells) and 24 i.m. (48 × 106 cells) injections of NurOwn® at 24 sites to the biceps and triceps

2014.05–2016.07

AEs

In a prespecified rapid progressor subgroup (n = 21), the rate of disease progression was improved at early time points.

 NCT02286011/ [30]

Phase I

20 participants

MNC of BM

Experimental group: an intramuscular infusion of autologous MNC of bone BM in TA muscle of one of the lower limbs (100–1200 million) diluted in 2 ml saline.

2014.11–2017.12

AEs

The intramuscular injection of BMMCs was safe and had an effect on the D50 index.

 NCT03241784/ [31]

Phase I

4 participants

Autologous T-regulatory lymphocytes

A total of 8 infusions of autologous Tregs (1 × 106 cells/kg) with concomitant subcutaneous IL-2 injections (3 times /week, 2 × 105 IU/m2/injection).

2016.05–2018.02

AEs

The numbers of Tregs and suppressive function increased after infusion and the increased suppressive function of Tregs correlated with slowing of progression rate.

Gene modification

 NCT01041222/ [32]

Phase I

33 participants

ISIS 333611

Four cohorts of eight patients received intrathecal infusion of ISIS 333611 at dose of 0.15 mg, 0.5 mg, 1.5 mg, 3 mg, respectively (randomized 6 drugs: 2 placebo/cohort).

2010.01–2012.01

Safety, pharmacokinetics tolerability

No dose-limiting toxicity was found at doses up to 3.0 mg.

Dose-dependent CSF and plasma concentrations were observed.

 NCT02623699/ [33]

Phase I/II

84 participants

Tofersen (BIIB067)

In each dose cohort (20, 40, 60, or 100 mg), participants were randomly assigned in a 3:1 ratio to receive five doses of tofersen or placebo, administered intrathecally for 12 weeks.

2016.01–2019.01

AEs

CSF SOD1 concentrations decreased at the highest concentration of tofersen administered intrathecally over a period of 12 weeks.

Excitotoxicity

 NCT00444613/ [34]

Phase II/III

373 participants

Mecobalamin (E0302)

Placebo (n = 124), 25 mg (n = 124) or 50 mg methylcobalamin (n = 125) administered intra-muscularly twice a week for 182 weeks.

2007.04–2014.03

Survival rate, ALSFRS-R

No significant efficacy was seen in the whole cohort. The treatment may prolong survival and retard symptomatic progression if started early (≤12 months’ duration).

Mitochondrial defects and apoptosis

 NCT01786603/ [35]

Phase II

80 participants

Rasagiline

Rasagiline group (n = 60): rasagiline 2 mg P.O. once a day for 12 months. Placebo group (n = 20): placebo 2 mg once a day for 12 months.

2013.11–2016.07

ALSFRS-R

Rasagiline was well tolerated with no serious adverse events. No improvement in the ALSFRS-R slope was observed in the rasagiline group.

 NCT01879241/ [36]

Phase II

252 participants

Rasagiline

Rasagiline group (n = 127): 100 mg riluzole plus 1 mg rasagiline P.O.Placebo group (n = 125): 100 mg riluzole plus placebo P.O. per day for 18 months.

2013.06–2016.08

Survival

Disease progression might be modified by rasagiline in patients with normal to fast progression rate, despite no efficacy in survival.

Immunomodulatory

 NCT02588677/ [37]

Phase II/III 394 participants

Masitinib

394 patients were randomly assigned (1:1:1) to receive riluzole (100 mg/d) plus placebo or masitinib at 4.5 or 3.0 mg/kg per day.

2013.04–2018.03

ALSFRS-R

Masitinib showed significant benefits over placebo with a between-group difference in â–³ALSFRS-R, corresponding to 27% slowing in the rate of functional decline.

  1. AEs adverse events, ALSFRS-R revised ALS functional rating scale, DLT dose-limiting toxicity, i.v. intravenous, HSSC human spinal stem cells, hNSCs fetal human neural stem cells from natural in utero death, BM-derived MSCs bone marrow-derived mesenchymal stem cells; i.m. intramuscular, i.t. intrathecal, MSC-NTF mesenchymal stem cells-neurotrophic factors, VC vital capacity, CSF cerebrospinal fluid, ISIS 333611 an antisense oligonucleotide designed to inhibit SOD1 expression, MNC mononuclear cells, BM bone marrow