The HIt HArd and hiT Early in Multiple Sclerosis Trial

NCT07517185 | Not Yet Recruiting Phase 2

• 2 other identifiers: HiHat2024-519700-28-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

Brief 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). 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

Keywords

rituximab; cladribine

Outcome Measures

Primary Outcomes (1)

• 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.

  From start of treatment until end of follow-up at 2 years.

Secondary Outcomes (7)

• Magnetic Resonance Imaging (MRI) lesions

  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

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

• Disability

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

• Symbol Digit Modalities Test (SDMT)

  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)

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

Study Arms (1)

Patients with relapsing-remitting multiple sclerosis (RRMS)

EXPERIMENTAL

The study population will consist of subjects with RRMS with less than 10 years disease duration.

Drug: Sequential treatment with rituximab and cladribine

Interventions

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.

Patients with relapsing-remitting multiple sclerosis (RRMS)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Uppsala University: lead

Study Sites (4)

Falu Lasarett, Neurologen

Falun, 79182, Sweden

Location

Gävle sjukhus, Neurologmottagningen

Gävle, 80324, Sweden

Location

Centralsjukhuset Karlstad, Neurologi och Rehabiliteringskliniken

Karlstad, 651 85, Sweden

Location

Uppsala University Hospital

Uppsala, 75185, Sweden

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Rituximab; Cladribine

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; 2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Joachim Burman, MD, PhD

CONTACT

+46 18 611 50 88; joachim.burman@uu.se

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: April 8, 2026
• Study Start: April 15, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (4)