Ocrelizumab or Alemtuzumab Compared With Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis - a Phase-2 Randomised Controlled Trial

NCT04971005 | Terminated Phase 2 DMC

• 1 other identifier: inims-009
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

Brief Summary

A multicentre controlled phase II trial to compare the efficacy and safety of ocrelizumab or alemtuzumab and autologous Hematopoietic Stem Cell Transplantation (aHSCT). Active relapsing-remitting MS-Patients will be included and randomised to ocrelizumab or alemtuzumab versus aHSCT. Primary endpoint will be the time to treatment failure as assessed by failure of NEDA (no evidence of disease activity) as represented by: no expanded disability status scale (EDSS) progression, no relapse, no new T2 lesion and no Gd-enhancing lesion. This trial offers the opportunity to gain further information about efficacy and safety of all treatments and will give new insights into the immunology of highly active RRMS.

Conditions

Relapsing-Remitting Multiple Sclerosis

Keywords

autologous hematopoetic stem cell transplantation; alemtzumab; ocrelizumab; randomised controlled trial; aggressive highly active multiple sclerosis; no evidence of diseae activity (NEDA)

Outcome Measures

Primary Outcomes (1)

• Time to treatment failure as assessed by failure of NEDA (no evidence of disease activity)

  Time to treatment failure as assessed by failure of NEDA (no evidence of disease activity) during follow-up as defined by: * 3 months confirmed EDSS (Expanded disability status scale) progression * confirmed relapse * new/enlarging T2-hyperintense lesion on MRI (Magnetic resonance imaging) * any Gd-enhancing lesion on MRI

  through study completion, on average at least 2 years

Secondary Outcomes (9)

• Efficacy of treatment defined by EDSS

  through study completion, on average at least 2 years

• Efficacy of treatment defined by the annualized relapse rate

  through study completion, on average at least 2 years

• Efficacy of treatment defined by the number of new T2 lesions

  through study completion, on average at least 2 years

• Efficacy of treatment defined by the number of Gd-enhancing lesions

  through study completion, on average at least 2 years

• Efficacy of treatment defined by multiple sclerosis functional composite (MSFC) change

  through study completion, on average at least 2 years

Study Arms (2)

Intervention (aHSCT)

EXPERIMENTAL

Autologous Hematopoietic Stem Cell Transplantation. Mobilisation will be performed with 2 g/m2 cyclophosphamide and 10 μg/kg G-CSF from day 5 until apheresis is completed. Conditioning will be 200 mg/kg cyclo-phosphamide and Anti-T-lymphocyteglobuline (Grafalon®, Neovii) with cu-mulative doses of 20 mg/kg given on day +1 (10 mg/kg) and day +2 (10 mg/kg).

Drug: Autologous Hematopoietic Stem Cell Transplantation

Control

ACTIVE COMPARATOR

In the control arm patient and physician will decide which treatment to choose. Patients will be either treated with ocrelizumab according to the SmPC (600 mg every 6 months continuously) or with alemtuzumab according to the SmPC (12 mg/day for 5 consecutive days and again after 365 days for 3 days).

Drug: Ocrelizumab; Drug: Alemtuzumab

Interventions

Autologous Hematopoietic Stem Cell Transplantation DRUG

Autologous Hematopoietic Stem Cell Transplantation

Intervention (aHSCT)

Ocrelizumab DRUG

600 mg every 6 months continuously

Control

Alemtuzumab DRUG

12 mg/day for 5 consecutive days and again after 365 days for 3 days

Control

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Written informed consent and agreement to comply to study protocol
• Age: 18-55 years
• EDSS: 0.0 - 6.0
• RRMS according to McDonald 2010
• \< 10 years of disease course after symptom onset
• Active disease with one of the following treatment failures occur-ring not earlier than 6 months after initiation of an approved DMT
• or more relapses within the last 12 months
• relapse within the last 12 months and a Gd-enhancing lesion on MRI \> 3 mm \> 3 months before or after relapse onset or 2 new T2-lesions
• On-going signs of MRI activity in the last 6 months (either Gd-en-hancing of ≥ 3 mm lesion at any exam in the last year; or more than 5 new T2 lesions (≥ 3 mm)
• Patients stable under natalizumab but who have to stop treatment due to an increasing PML risk are defined as active, if a MRI within 6 months after termination of natalizumab shows new T2 or Gd-enhancing lesions and at least one other treatment fail-ure prior to natalizumab is documented.

You may not qualify if:

• Secondary or primary progressive MS
• Pregnancy, or other medical condition incompatible with aHSCT
• Any treatment or medical condition that, according to the haematologist / transplant specialist precludes the use of aHSCT
• John Cunningham virus (JCV) antibody index of \> 1.5 in previ-ously natalizumab-treated patients, if a negative CSF JCV-PCR prior to screening is not available
• Relapse during 30 days before initiation of treatment. If a relapse occurs during this period and eligibility criteria are otherwise ful-filled, start of treatment will be delayed until at least 30 days after receiving steroids.
• Concurrent clinically significant (as determined by the investiga-tors and haematologist / transplant specialist) cardiac, immuno-logical, pulmonary, neurological, renal or other major disease such as:
• Prominent cardial disease (Left ventricular ejection frac-tion (LVEF) \< 40%, myocardial infarction or ischemia, un-controlled arrhythmias, pericardial effusion \> 1 cm)
• Cerebrovascular disease
• Renal disease (creatinine clearance \< 30 ml/min/m2)
• Respiratory disease (DLCO \< 40% predicted)
• Active bleeding or clotting disease
• History of human immunodeficiency virus (HIV) or posi-tive HIV antibody testing
• Any uncontrolled acute or chronic infection, including HIV, hepatitis B surface antigen positivity and hepatitis C PCR positivity
• Cancer except in situ cervix or cutaneous
• Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, men-tal, or social) that is likely to affect the patient returning for follow-up visits on schedule. Unwillingness to use contraception.

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead
• Neovii Biotech: collaborator
• Clinical Trial Center North (CTC North GmbH & Co. KG): collaborator

Study Sites (2)

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Universitätsklinikum Mannheim

Mannheim, 68167, Germany

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

ocrelizumab; Alemtuzumab

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, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Nicolaus Kröger, Prof. Dr.

  University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Patients will be randomised to control (ocrelizumab or alemtuzumab) or intervention (aHSCT).

Study Record Dates

• First Submitted: August 12, 2020
• First Posted: July 21, 2021
• Study Start: August 27, 2021
• Primary Completion: February 4, 2022
• Study Completion: February 4, 2022
• Last Updated: March 16, 2022

Record last verified: 2022-03

Locations

DE (2)