A Phase 2 interventional study of Sequential treatment with rituximab and cladribine in Relapsing-remitting Multiple Sclerosis, sponsored by Uppsala University. Recruiting at 4 sites in Sweden. Open to participants aged 18 Years to 50 Years. Per ClinicalTrials.gov, last updated 2026-10-22.
Sponsored by Uppsala University · Phase 2, Interventional, and Treatment
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.
618 studies on the registry are indexed under Multiple Sclerosis, Relapsing-Remitting; 82 are open to participants now.
This study's planned enrollment of 60 is close to the median of 66 across 437 interventional studies indexed under Multiple Sclerosis, Relapsing-Remitting.
Browse Multiple Sclerosis, Relapsing-Remitting studies →Uppsala University is the lead sponsor of 390 studies on the registry; 86 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The study population will consist of subjects with RRMS with less than 10 years disease duration.
Drug: Sequential treatment with rituximab and cladribine
Drug pages: Rituximab · Cladribine
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.
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.
Time frame: From start of treatment until end of follow-up at 2 years.
Magnetic Resonance Imaging (MRI) lesions
Proportion of patients with a new MRI lesion will be reported.
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
The proportion of patients with at least one confirmed clinical relapse will be reported.
Time frame: 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).
Time frame: 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.
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)
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.
Time frame: 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.
Time frame: 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.
Time frame: From start of treatment to end of follow-up at 2 years.
Plan to share: No
No publications or documents are linked to this record.
Started Sep 2026 (actual). Primary completion is estimated for Dec 2030, 51 months after the start.
Of 25 phase 2 interventional studies under Multiple Sclerosis, Relapsing-Remitting, half reached primary completion within 41 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 67. This study's planned 51 months is above that.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drugs tested here: Rituximab · Cladribine
Multiple Sclerosis, Relapsing-Remitting →