Skip to main content
OpenTrials
Not Yet Recruiting

NCT Number: NCT07517185

The HIt HArd and hiT Early in Multiple Sclerosis Trial

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.

Not Yet Recruiting

Trial opening soon.

Get Notified

Key information

Conditions

Relapsing-Remitting Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Immune System Diseases Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting Nervous System Diseases

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Falu Lasarett, Neurologen, Falun, Sweden

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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,
  • 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.

Treatment and study plan

Sequential treatment with rituximab and cladribine

Drug

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.

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

    Proportion of patients with a new MRI lesion will be reported.

  2. Relapses

    Time frame: From start of treatment until the end of follow-up at 2 years.

    The proportion of patients with at least one confirmed clinical relapse will be reported.

  3. Disability

    Time frame: EDSS at baseline will be compared with EDSS at end of follow-up at 2 years.

    The proportion of patients with confirmed disability worsening, rated with the Kurtzke Expanded Disability Status Scale (EDSS, ranges from 0 to 10).

  4. Symbol Digit Modalities Test (SDMT)

    Time frame: SDMT at baseline is compared with SDMT at end of follow-up at 2 years.

    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.

  5. Quality of life (physical) measured by MSIS-29 (Multiple Sclerosis Impact Scale)

    Time frame: Baseline compared with end of follow-up at 2 years.

    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.

  6. Quality of life (MSIS-29 psychological)

    Time frame: Baseline compared with end of follow-up at 2 years.

    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.

  7. Treatment-related Adverse Events

    Time frame: From start of treatment to end of follow-up at 2 years.

    The proportion of patients with treatment-related adverse events of mild or moderate severity (relationship ≥ probable) to the study medication.

Study contacts

Contact information is provided by the study sponsor or research team.

Joachim Burman, MD, PhD

CONTACT

[email protected]

+46 18 611 50 88

Sponsors and collaborators

Lead sponsor

Uppsala University

Other

Registry information

Official study 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

Acronym: HiHat

Important dates

Study start
2026
Primary completion
2030
Study completion
2030
First posted
Apr 8, 2026
Registry last updated
Apr 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.