HiHat trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Uppsala

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2025-10-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

The primary objective of the study is to evaluate whether the SAE rate associated with sequential treatment of rituximab followed by cladribine is acceptably low.

Secondary objectives 6

1. To investigate the effect of sequential treatment with rituximab and cladribine on MRI lesions
2. To investigate the effect of sequential treatment with rituximab and cladribine on relapses.
3. To investigate the effect of sequential treatment with rituximab and cladribine on disability.
4. To investigate the effect of sequential treatment with rituximab and cladribine on tissue injury.
5. To investigate the effect of sequential treatment with rituximab and cladribine on quality of life.
6. To investigate the effect of sequential treatment with rituximab and cladribine on safety.

Conditions and MedDRA coding

Patients with relapsing-remitting multiple sclerosis with less than 10 years disease duration.

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Diagnosis of RRMS according to the 2017 revised McDonald criteria.
2. Disease activity within the preceding year in the form of: (a) a clinical relapse, and/or (b) evidence of ≥2 T2 lesions on MRI scan, and or (c) presence of gadolinium enhancing lesions on an MRI scan
3. Age 18 – 50 years (inclusive) of age
4. Disease duration ≤10 years (since MS diagnosis)
5. EDSS 0 – 5.5 (inclusive)
6. Signed informed consent

Exclusion criteria 14

1. Diagnosis of progressive MS.
2. Previous use of rituximab (or any other B-dell depleting monoclonal antibody) and/or cladribine
3. Pregnant or lactating women, s-HCG will be tested on all women at screening and in any situation where there is a reason to suspect pregnancy during the trial, e.g. delayed menstruation.
4. Unwilling to use contraception during the treatment period and the first year after completing the treatment course.
5. Patients having contraindication for or otherwise not compliant with MRI investigations.
6. Simultaneous treatment with other immunosuppressive drugs.
7. Infection with human immunodeficiency virus (HIV)
8. Active, severe infections (e.g. hepatitis or tuberculosis). Signs of infections are assessed before inclusion and each study-related infusion through clinical examination and further evaluated by laboratory and other relevant investigations in case of suspected ongoing infection.
9. Severe cardiac disorder. E.g. signs of congestive heart failure or coronary artery disease. This will be evaluated through clinical assessment before inclusion.
10. Moderate or severe renal impairment. Estimated glomerular filtration rate (eGFR) <60.
11. Active malignancy
12. No prior exposure to varicella virus. This is assessed through varicella serology.
13. Vaccination within 4 weeks of first dose of study medication
14. Severe psychiatric condition.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The binary indicator of at least one treatment-related SAE (relationship ≥ possible) per participant.

Secondary endpoints 6

1. Proportion of patients with a new MRI lesion at end of follow-up; and the average number of new T2 lesions per patient.
2. Proportion of patients with a new relapse; and the proportion of patients with a steroid-treated relapse; and the annualized relapse rate during follow-up,
3. Proportion of patients with confirmed disability worsening; and the average change in EDSS (Expanded Disability Status Scale); and proportion of patients with worsened/unchanged/improved SDMT; and the average change in SDMT.
4. The average change in pNfL and pGFAp.
5. Proportion of patients with improved MSIS-29; and the average change in MSIS-29.
6. Proportion of patients with mild/moderate adverse events with at least a probable relationship to the study medication (adverse reaction)

Investigational products

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

Test 2

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Uppsala

Sponsor organisation

Region Uppsala

Address

Storgatan 27, Uppsala Domkyrkofors. Uppsala Domkyrkofors.

City

Uppsala

Postcode

753 31

Country

Sweden

Scientific contact point

Organisation

Region Uppsala

Contact name

Department of Neurology

Public contact point

Organisation

Region Uppsala

Contact name

Department of Neurology

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Results and documents

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

Documents 8 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