Relapsing-remitting Multiple SclerosisPhase 2HiHatNCT07517185
The HIt HArd and hiT Early in Multiple Sclerosis Trial
A Phase 2 study testing Sequential treatment with rituximab and cladribine in people with Relapsing-remitting Multiple Sclerosis, run by Uppsala University at 4 sites in Sweden.
Trial summary
The HiHat trial is a Phase 2 study aimed at evaluating the safety and feasibility of sequential treatment with rituximab and cladribine in patients with relapsing-remitting multiple sclerosis (RRMS). Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Relapsing-remitting Multiple Sclerosis
- What is being tested?
- Sequential treatment with rituximab and cladribine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 4 sitesSweden
- Study dates
- 1 Sep 2026to 31 Dec 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosis of RRMS according to the 2017 revised McDonald criteria,
- With disease activity within the preceding year in the form of: a clinical relapse, and/or evidence of ≥2 T2 lesions on MRI scan, and or presence of gadolinium enhancing lesions on an MRI scan,
- Age 18 - 50 years (inclusive) of age,
- Disease duration ≤10 years (since MS diagnosis),
- EDSS 0 - 5.5 (inclusive),
- Signed informed consent.
Who cannot join
- Diagnosis of progressive MS,
- Previous use of rituximab (or any other B-cell depleting monoclonal antibody) and/or cladribine,
- Pregnant or lactating women,
- Unwilling to use contraception during the treatment period and the first year after completing the treatment course,
- Patients having contraindication for or otherwise not compliant with MRI investigations,
- Simultaneous treatment with other immunosuppressive drugs,
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- Infection with human immunodeficiency virus (HIV),
- Active, severe infections (e.g. hepatitis or tuberculosis),
- Severe cardiac disorder,
- Moderate or severe renal impairment (eGFR <60).
- Active malignancy,
- No prior exposure to varicella virus,
- Vaccination within 4 weeks of first dose of study medication,
- Severe psychiatric condition.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Sweden4 sites, 4 recruiting
- Recruiting
Falu Lasarett, Neurologen
Falun, 79182
Martin Othozon, MD, +46 23 490000, martin.othozon@regiondalarna.se
- Not yet recruiting
Gävle sjukhus, Neurologmottagningen
Gävle, 80324
Sara Moussavi, MD, +46 26 15 43 44, kliniskaprovningar@regiongavleborg.se
- Recruiting
Centralsjukhuset Karlstad, Neurologi och Rehabiliteringskliniken
Karlstad, 651 85
Oskar Wickberg, MD, +46 10 8315000, oskar.wickberg@regionvarmland.se
- Recruiting
Uppsala University Hospital
Uppsala, 75185
Joachim Burman, MD, PhD, +46 18 611 5088, joachim.burman@uu.se
About this study
Official title: The HIt HArd and hiT Early in Multiple Sclerosis Trial - HiHat Trial A Phase 2 Study of Sequential Treatment With Rituximab and Cladribine for Relapsing-remitting Multiple Sclerosis
The HiHat trial is a Phase 2 study aimed at evaluating the safety and feasibility of sequential treatment with rituximab and cladribine in patients with relapsing-remitting multiple sclerosis (RRMS). The study follows a prospective, open-label, single-arm design, with 60 RRMS patients receiving both treatments in a controlled regimen: two cycles of rituximab (1,000 mg each, biweekly) followed by two cycles of cladribine (30 mg per cycle for three days per cycle) spaced one month apart. Participants are monitored over 24 months through clinical assessments, MRI, and biomarker analyses. The primary objective is to evaluate whether the rate of serious adverse events (SAE) is acceptably low. Secondary objectives include assessing impacts on MRI lesion count, relapse rates, disability progression, quality of life, and safety.
- Conditions
- Relapsing-remitting Multiple Sclerosis
- Being tested
- Sequential treatment with rituximab and cladribine
- Keywords
- rituximab, cladribine
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sequential treatment with rituximab and cladribineDrug
Two cycles of rituximab (1,000 mg each, biweekly) followed by two cycles of cladribine (30 mg per cycle for three days per cycle) spaced one month apart.
| Study group | Role | What they receive |
|---|---|---|
| Patients with relapsing-remitting multiple sclerosis (RRMS) | Experimental | The study population will consist of subjects with RRMS with less than 10 years disease duration. Receives: Drug: Sequential treatment with rituximab and cladribine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-related Serious Adverse Events
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. The proportion of patients with at least one treatment-related SAE (relationship ≥ possible) will be reported.
Measured: From start of treatment until end of follow-up at 2 years.
Secondary outcomes (7)
Magnetic Resonance Imaging (MRI) lesions
Proportion of patients with a new MRI lesion will be reported.
Measured: The first scan made after the treatment course has been completed (week 12) will be compared with the scan at 2 years to determine if new lesions have occurred.
Relapses
The proportion of patients with at least one confirmed clinical relapse will be reported.
Measured: From start of treatment until the end of follow-up at 2 years.
Disability
The proportion of patients with confirmed disability worsening, rated with the Kurtzke Expanded Disability Status Scale (EDSS, ranges from 0 to 10).
Measured: EDSS at baseline will be compared with EDSS at end of follow-up at 2 years.
Symbol Digit Modalities Test (SDMT)
The proportion of patients with worsened, unchanged, or improved SDMT (score range 0-110, higher numbers are better) will be reported. A change by at least 4 points on the SDMT will be considered a clinically meaningful change.
Measured: SDMT at baseline is compared with SDMT at end of follow-up at 2 years.
Quality of life (physical) measured by MSIS-29 (Multiple Sclerosis Impact Scale)
The proportion of patients with improvement in MSIS-29 physical (rated 0-100, higher is worse) will be reported. A change by 8 points in the physical domain will be considered a clinically meaningful change.
Measured: Baseline compared with end of follow-up at 2 years.
Quality of life (MSIS-29 psychological)
The proportion of patients with improvement in MSIS-29 psychological (rated 0-100, higher is worse) will be reported. A change by 6 points in the psychological domain will be considered a clinically meaningful change.
Measured: Baseline compared with end of follow-up at 2 years.
Treatment-related Adverse Events
The proportion of patients with treatment-related adverse events of mild or moderate severity (relationship ≥ probable) to the study medication.
Measured: From start of treatment to end of follow-up at 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2026
- Study start1 Sep 2026
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsing-remitting Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Uppsala UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Uppsala University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07517185
- Sponsor's protocol ID
- HiHat
- Other IDs
- 2024-519700-28-01
- Acronym
- HiHat
- Status last verified
- Oct 2026
- First submitted
- 21 Nov 2025
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The HIt HArd and hiT Early in Multiple Sclerosis Trial - HiHat Trial A Phase 2 Study of Sequential Treatment With Rituximab and Cladribine for Relapsing-remitting Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT07517185
- Acronym / sponsor ID
- HiHat / HiHat
- Conditions
- Relapsing-remitting Multiple Sclerosis
- Keywords
- rituximab, cladribine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Uppsala UniversityUniversity, hospital or other
- Study start
- 1 Sep 2026 (actual)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 8 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The HiHat trial is a Phase 2 study aimed at evaluating the safety and feasibility of sequential treatment with rituximab and cladribine in patients with relapsing-remitting multiple sclerosis (RRMS). The study follows a prospective, open-label, single-arm design, with 60 RRMS patients receiving both treatments in a controlled regimen: two cycles of rituximab (1,000 mg each, biweekly) followed by two cycles of cladribine (30 mg per cycle for three days per cycle) spaced one month apart. Participants are monitored over 24 months through clinical assessments, MRI, and biomarker analyses. The primary objective is to evaluate whether the rate of serious adverse events (SAE) is acceptably low. Secondary objectives include assessing impacts on MRI lesion count, relapse rates, disability progression, quality of life, and safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with relapsing-remitting multiple sclerosis (RRMS) | Experimental | Drug: Sequential treatment with rituximab and cladribineThe study population will consist of subjects with RRMS with less than 10 years disease duration. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Diagnosis of RRMS according to the 2017 revised McDonald criteria,
- With disease activity within the preceding year in the form of: a clinical relapse, and/or evidence of ≥2 T2 lesions on MRI scan, and or presence of gadolinium enhancing lesions on an MRI scan,
- Age 18 - 50 years (inclusive) of age,
- Disease duration ≤10 years (since MS diagnosis),
- EDSS 0 - 5.5 (inclusive),
Key exclusion criteria (14 listed)
- Diagnosis of progressive MS,
- Previous use of rituximab (or any other B-cell depleting monoclonal antibody) and/or cladribine,
- Pregnant or lactating women,
- Unwilling to use contraception during the treatment period and the first year after completing the treatment course,
- Patients having contraindication for or otherwise not compliant with MRI investigations,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sequential treatment with rituximab and cladribineTwo cycles of rituximab (1,000 mg each, biweekly) followed by two cycles of cladribine (30 mg per cycle for three days per cycle) spaced one month apart. | Drug | Patients with relapsing-remitting multiple sclerosis (RRMS) |
Primary outcome
Treatment-related Serious Adverse Events
Time frame: From start of treatment until end of follow-up at 2 years.
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. The proportion of patients with at least one treatment-related SAE (relationship ≥ possible) will be reported.
7 secondary outcomes
Magnetic Resonance Imaging (MRI) lesions
Time frame: The first scan made after the treatment course has been completed (week 12) will be compared with the scan at 2 years to determine if new lesions have occurred.
Relapses
Time frame: From start of treatment until the end of follow-up at 2 years.
Disability
Time frame: EDSS at baseline will be compared with EDSS at end of follow-up at 2 years.
Symbol Digit Modalities Test (SDMT)
Time frame: SDMT at baseline is compared with SDMT at end of follow-up at 2 years.
Quality of life (physical) measured by MSIS-29 (Multiple Sclerosis Impact Scale)
Time frame: Baseline compared with end of follow-up at 2 years.
Quality of life (MSIS-29 psychological)
Time frame: Baseline compared with end of follow-up at 2 years.
Treatment-related Adverse Events
Time frame: From start of treatment to end of follow-up at 2 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sequential treatment with rituximab and cladribine in people with Relapsing-remitting Multiple Sclerosis, run by Uppsala University at 4 sites in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Joachim Burman, MD, PhD (+46 18 611 50 88, joachim.burman@uu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment-related Serious Adverse Events (time frame: From start of treatment until end of follow-up at 2 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2026.