Relapsing-remitting Multiple Sclerosis
Conditions
Keywords
rituximab, cladribine
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.
Interventions
DRUGSequential treatment with rituximab and 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.
Sponsors
Uppsala University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-related Serious Adverse Events | 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
| Measure | Time frame | Description |
|---|---|---|
| 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. | Proportion of patients with a new MRI lesion will be reported. |
| Relapses | 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. |
| Disability | 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). |
| Symbol Digit Modalities Test (SDMT) | 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. |
| Quality of life (physical) measured by MSIS-29 (Multiple Sclerosis Impact Scale) | 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. |
| Quality of life (MSIS-29 psychological) | 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. |
| Treatment-related Adverse Events | 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. |
Countries
Sweden
Contacts
CONTACTJoachim Burman, MD, PhD
Outcome results
None listed