MANUS trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Utrecht

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17], Diseases [C] - Immune System Diseases [C20]

Trial duration

1 Nov 2024 → ongoing

Decision date (initial)

2024-10-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

ZonMW, the Netherlands

External identifiers

EU CT number

2024-515387-31-00

EudraCT number

2015-000168-32

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To investigate whether in patients with peripheral vascular complications related to SSc, intramuscular allogeneic BM-MSC therapy is
feasible, safe and potentially effective

Secondary objectives 1

1. To assess the accuracy of various parameters related to inflammation, endothelial activation and neovascularization to predict therapeutic efficacy and/or serve as biomarkers

Conditions and MedDRA coding

Systemic Sclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age >18 years
2. Established diagnosis of SSc according to criteria of the American College of Rheumatology (2013)
3. At least one active digital ulcer (painful area, >2 mm in diameter with visible depth and loss of dermis) refractory to 5 days intravenous prostacyclines
4. informed consent

Exclusion criteria 7

1. Ulcer with underlying calcinosis (ruled out by X-ray prior to screening/inclusion)
2. History of neoplasm or malignancy in the past 10 years
3. Pregnancy or unwillingness to use adequate contraception during study
4. Serious known concomitant disease with life expectancy <1 year
5. Uncontrolled hypertension
6. Uncontrolled acute or chronic infection
7. follow-up impossible

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome is the toxicity of the treatment at 12 weeks after MSC administration, defined as -1. Local toxicity, including signs of local inflammation (swelling, warmth, impairment of function), worsening of ulcers or new ulcers or hematomes after MSC administration - 2. Other adverse events, graded according to the Common Terminology Criteria for Adverse Events.

Secondary endpoints 11

1. A secondary outcome measure for safety is the incidence (at 12 weeks post treatment) of any treatment-related serious adverse events (SAE) defined as events leading to hospitalization, death, or persistent or significant disability
2. Change in pain as assessed using the Numerical Rating Scale, the digital ulcer visual analogue scale (part of the S-HAQ), pain VAS (S-HAQ), use of analgesics.
3. Quality of life and disability as assessed with the HAQ-disability index, and the SF-36, EuroQol (EQ-5D) questionnaires
4. Hand function as assessed with the Cochin Hand Function Scale.
5. Number of digital ulcers 12 weeks post treatment
6. Change in the number of active tip digital ulcers on the volar aspect
7. Need to alter medication regime as determined by the patient’s own rheumatologist
8. The severity of scleroderma as assessed with the Modified Rodnan skin score 79 and the Scleroderma Health Assessment Questionnaire (S-HAQ)
9. Number and severity of Raynaud’s symptoms, as assessed using the Raynaud Condition Score
10. Changes in capillary morphology and architecture, as visualized with video-assisted nailfold capillaroscopy by a trained investigator
11. Changes in laboratory parameters

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Utrecht

Sponsor organisation

Universitair Medisch Centrum Utrecht

Address

Heidelberglaan 100

City

Utrecht

Postcode

3584 CX

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

prof. dr. M.C. Verhaar

Public contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

prof. dr. M.C. Verhaar

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications