Trial Outcomes & Findings for Stem Cells in Rapidly Evolving Active Multiple Sclerosis (NCT NCT01606215)

NCT ID: NCT01606215

Last Updated: 2025-01-14

Results Overview

The number of adverse events before crossover in the stem cell treatment group compared to the placebo group over the first 24 weeks (please refer to period 1 of the participant flow).

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 21 participants
• Primary outcome timeframe: 24 weeks from baseline
• Results posted on: 2025-01-14

Participant Flow

21 patients screened into trial and having bone marrow aspiration

Bone marrow aspiration and expansion in the stem cell laboratory. Continuation in trial required expansion of MSCs to 1-2 x106 million MSCs/kg Of the 21 patients screened, only 13 continued in the trial (others failed MSC expansion and do not contribute to results)

Participant milestones

Measure	A: Mesenchymal Stem Cells First, Then Placebo 1-2 x106 MSCs/kg administered at Week 0 Mesenchymal stem cells: 1.0-2.0 million cells/kg body weight	B: Placebo First, Then MSCs Suspension media administered at Week 0 Placebo: Placebo
Treatment to 1st Group - Placebo to 2nd STARTED	10	11
Treatment to 1st Group - Placebo to 2nd COMPLETED	6	7
Treatment to 1st Group - Placebo to 2nd NOT COMPLETED	4	4
Follow-up STARTED	6	7
Follow-up COMPLETED	6	7
Follow-up NOT COMPLETED	0	0
Placebo to 1st Group - Treatment to 2nd STARTED	6	7
Placebo to 1st Group - Treatment to 2nd COMPLETED	6	7
Placebo to 1st Group - Treatment to 2nd NOT COMPLETED	0	0

Reasons for withdrawal

Measure	A: Mesenchymal Stem Cells First, Then Placebo 1-2 x106 MSCs/kg administered at Week 0 Mesenchymal stem cells: 1.0-2.0 million cells/kg body weight	B: Placebo First, Then MSCs Suspension media administered at Week 0 Placebo: Placebo
Treatment to 1st Group - Placebo to 2nd Failure to expand autologous mesenchymal stem cell product according to protocol specifications	4	4

Baseline Characteristics

Stem Cells in Rapidly Evolving Active Multiple Sclerosis

Baseline characteristics by cohort

Measure	A: Mesenchymal Stem Cells First, Then Placebo n=6 Participants Mesenchymal stem cells first, then placebo: Mesenchymal stem cells; 1.0-2.0 million cells/kg body weight (1-2 x106 MSCs/kg administered at Week 0)	B: Placebo First, Then MSCs n=7 Participants Placebo first, then MSCs: Placebo; Placebo (Suspension media administered at Week 0)	Total n=13 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment United Kingdom	6 participants n=5 Participants	7 participants n=7 Participants	13 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks from baseline

The number of adverse events before crossover in the stem cell treatment group compared to the placebo group over the first 24 weeks (please refer to period 1 of the participant flow).

Outcome measures

Measure	A: Mesenchymal Stem Cells First, Then Placebo n=6 Participants 1-2 x106 MSCs/kg administered at Week 0 Mesenchymal stem cells: 1.0-2.0 million cells/kg body weight	B: Placebo First, Then MSCs n=7 Participants Suspension media administered at Week 0 Placebo: Placebo
Number of Adverse Events Assessed by CTCAE v4.0	5 total events	0 total events

PRIMARY outcome

Timeframe: Up to 24 weeks

Population: Comparison of GELs between MSC- vs placebo- treated groups up to Week 24

Where GELs stands for gadolinium enhancing lesions and MSC for Mesenchymal Stem Cell.

This was to evaluate the efficacy of autologous mesenchymal stem cells in MS patients, quantified by the reduction in the number of new gadolinium-enhancing lesions counted on MRI scans over 24 weeks and the total number of GELs counted over months 1, 3 and 6 will be compared between treatment groups.

Outcome measures

Measure	A: Mesenchymal Stem Cells First, Then Placebo n=6 Participants 1-2 x106 MSCs/kg administered at Week 0 Mesenchymal stem cells: 1.0-2.0 million cells/kg body weight	B: Placebo First, Then MSCs n=7 Participants Suspension media administered at Week 0 Placebo: Placebo
Number of GELs Newly Appearing at Weeks 4, 12 and 24 After MSC Therapy in the First 24 Weeks of Trial Week 0 to 4	1.5 number of GELS counted Standard Deviation 2.07	1.29 number of GELS counted Standard Deviation 2.98
Number of GELs Newly Appearing at Weeks 4, 12 and 24 After MSC Therapy in the First 24 Weeks of Trial Week 4 to 12	1.5 number of GELS counted Standard Deviation 2.25	2.29 number of GELS counted Standard Deviation 4.39
Number of GELs Newly Appearing at Weeks 4, 12 and 24 After MSC Therapy in the First 24 Weeks of Trial Week 12 to 24	1.17 number of GELS counted Standard Deviation 0.75	2.43 number of GELS counted Standard Deviation 4.89

SECONDARY outcome

Timeframe: Months 1, 3 and 6

Number of gadolinium enhancing lesions identified over months 1, 3 and 6 will be compared between treatment groups - the treatment groups in this section relate to all 13 patients treated with MSCs (so patients in arm MSCs first, then placebo and 7 patients in placebo first, then MSCs) with 7 placebo patients (placebo first, then MSCs - the placebo group here ignores the 6 pts treated with MSCs first as we do not know whether there is any ongoing effect of MSCs beyond 24 weeks).

Outcome measures

Measure	A: Mesenchymal Stem Cells First, Then Placebo n=13 Participants 1-2 x106 MSCs/kg administered at Week 0 Mesenchymal stem cells: 1.0-2.0 million cells/kg body weight	B: Placebo First, Then MSCs n=7 Participants Suspension media administered at Week 0 Placebo: Placebo
Number of Newly Appearing GELs Over Months 1, 3 and 6 Will be Compared Between Treatment Groups. Week 0 to 4	1.38 number of GELS counted Standard Deviation 1.71	1.29 number of GELS counted Standard Deviation 2.98
Number of Newly Appearing GELs Over Months 1, 3 and 6 Will be Compared Between Treatment Groups. Week 4 to 12	1.92 number of GELS counted Standard Deviation 2.75	2.29 number of GELS counted Standard Deviation 4.39
Number of Newly Appearing GELs Over Months 1, 3 and 6 Will be Compared Between Treatment Groups. Week 12 to 24	1.46 number of GELS counted Standard Deviation 1.90	2.43 number of GELS counted Standard Deviation 4.89

SECONDARY outcome

Timeframe: Months 6-12

Population: crossover phase of trial; weeks 24-48

The number of contrast enhancing lesions counted over months 7, 9 and 12 (that is after cross-over).

Outcome measures

Measure	A: Mesenchymal Stem Cells First, Then Placebo n=6 Participants 1-2 x106 MSCs/kg administered at Week 0 Mesenchymal stem cells: 1.0-2.0 million cells/kg body weight	B: Placebo First, Then MSCs n=7 Participants Suspension media administered at Week 0 Placebo: Placebo
Comparison of Contrast Enhancing Lesions Between Treatment Periods Following Crossover Week 28	2.5 number of GELS counted Standard Deviation 2.35	1.29 number of GELS counted Standard Deviation 1.50
Comparison of Contrast Enhancing Lesions Between Treatment Periods Following Crossover Week 36	2.33 number of GELS counted Standard Deviation 2.94	2.29 number of GELS counted Standard Deviation 3.25
Comparison of Contrast Enhancing Lesions Between Treatment Periods Following Crossover Week 48	1.5 number of GELS counted Standard Deviation 1.87	1.71 number of GELS counted Standard Deviation 2.56

SECONDARY outcome

Timeframe: Weeks 4, 12 and 24

Population: after crossover treatment

To evaluate the efficacy of autologous mesenchymal stem cells in MS patients, quantified by the reduction in combined unique MRI activity on MRI scans over 24 weeks. The total number of such lesions counted over Weeks 4, 12 and 24 will be compared between treatment groups.

Combined Unique MRI activity defined as number of new T1w contrast-enhanced lesions plus number of new T2w lesions without contrast enhancement on T1w plus number of enlarging T2w lesions (>50% volume increase, no lesion fusion) without contrast enhancement on T1w.

Outcome measures

Measure	A: Mesenchymal Stem Cells First, Then Placebo n=6 Participants 1-2 x106 MSCs/kg administered at Week 0 Mesenchymal stem cells: 1.0-2.0 million cells/kg body weight	B: Placebo First, Then MSCs n=7 Participants Suspension media administered at Week 0 Placebo: Placebo
Combined Unique MRI Activity Week 4	1.5 combined unique MRI activity Standard Deviation 2.07	2 combined unique MRI activity Standard Deviation 3.70
Combined Unique MRI Activity Week 12	2.17 combined unique MRI activity Standard Deviation 3.07	3.14 combined unique MRI activity Standard Deviation 5.05
Combined Unique MRI Activity Week 24	1.83 combined unique MRI activity Standard Deviation 1.60	4.43 combined unique MRI activity Standard Deviation 8.90

SECONDARY outcome

Timeframe: 6 months

number of relapses in MSC treatment group vs. placebo group in the first 6 months

Outcome measures

Measure	A: Mesenchymal Stem Cells First, Then Placebo n=6 Participants 1-2 x106 MSCs/kg administered at Week 0 Mesenchymal stem cells: 1.0-2.0 million cells/kg body weight	B: Placebo First, Then MSCs n=7 Participants Suspension media administered at Week 0 Placebo: Placebo
Relapses	2 total events	10 total events

SECONDARY outcome

Timeframe: 6 months

EDSS at 6 months in both groups at Week 24: comparing 'MSCs first, then placebo' and 'Placebo first, then MSCs' at Week 24.

EDSS is a disability score. EDSS is an abbreviation for Expanded Disability Status Scale. Ranges from 0 (no disability) to 10 (death). A higher score indicates worsening disability.

Outcome measures

Measure	A: Mesenchymal Stem Cells First, Then Placebo n=6 Participants 1-2 x106 MSCs/kg administered at Week 0 Mesenchymal stem cells: 1.0-2.0 million cells/kg body weight	B: Placebo First, Then MSCs n=7 Participants Suspension media administered at Week 0 Placebo: Placebo
Progression of Disability	4.0 score on a scale (EDSS) Standard Deviation 1.0	3.9 score on a scale (EDSS) Standard Deviation 1.77

Adverse Events

A: Mesenchymal Stem Cell Tratment First

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

B: Placebo First

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	A: Mesenchymal Stem Cell Tratment First n=10 participants at risk 1-2 x106 MSCs/kg administered first Mesenchymal stem cells: 1.0-2.0 million cells/kg body weight second	B: Placebo First n=11 participants at risk Suspension media administered first Placebo: Placebo second
Ear and labyrinth disorders tinnitus	10.0% 1/10 • Number of events 1 • 12 months	0.00% 0/11 • 12 months
Musculoskeletal and connective tissue disorders back pain	30.0% 3/10 • Number of events 3 • 12 months	0.00% 0/11 • 12 months
Renal and urinary disorders urinary tract infection	10.0% 1/10 • Number of events 1 • 12 months	0.00% 0/11 • 12 months

Additional Information

Professor Paolo Muraro

Imperial College London

Phone: 02075946670

Email: p.muraro@imperial.ac.uk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place