Relapsing-Remitting Multiple SclerosisPhase 2COASTNCT04971005
Ocrelizumab or Alemtuzumab Compared With Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis - a Phase-2 Randomised Controlled Trial
A Phase 2 study testing Autologous Hematopoietic Stem Cell Transplantation, Ocrelizumab and Alemtuzumab in people with Relapsing-Remitting Multiple Sclerosis, run by Universitätsklinikum Hamburg-Eppendorf at 2 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Relapsing-Remitting Multiple Sclerosis
- What is being tested?
- Autologous Hematopoietic Stem Cell Transplantation, Ocrelizumab and Alemtuzumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 2 sitesGermany
- Study dates
- 27 Aug 2021to 4 Feb 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
None listed.
Who cannot join
- 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:
Show all 24Show fewer
- 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.
- Previous participation in this study, previous treatment with aHSCT or already both comparators
- Ongoing immunotherapy. Treatment with interferon or glati-rameracetate will need no wash-out. Treatment pause before oc-relizumab/alemtuzumab or aHSCT will be:
- for dimethylfumarate and fingolimod: 8 weeks
- for natalizumab: 8 weeks
- for ocrelizumab: 12 weeks
- for alemtuzumab: 12 months
- for teriflunomide: 4 weeks after elimination with cholesty-ramine
- for cladribine: 24 weeks
- Patients with cognitive impairments who are unable to provide written, informed consent prior to any testing under this protocol, including screening and baseline investigations that are not con-sidered part of routine patient care.
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246
Universitätsklinikum Mannheim
Mannheim, 68167
About this study
Official title: A Randomised Controlled Trial to Compare Ocrelizumab or Alemtuzumab With Autologous Hematopoietic Stem Cell Transplantation (aHSCT) in High Inflammatory Multiple Sclerosis (COAST)
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.
Read the detailed description
A rater-blinded multicentre randomised controlled phase II trial to compare the efficacy and safety of ocrelizumab or alemtuzumab and aHSCT. Active RRMS-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.
aHSCT appears highly efficacious in reducing inflammatory disease activity and relapses in active relapsing-remitting MS. Cohort data show a long-term stagnation of inflammatory disease activity for up to 10 years and more after aHSCT. However, efficacy data from randomised controlled trials comparing aHSCT with approved treatments are still lacking.
The best available data concerning disease activity in MS patients with a documented treatment failure are from the CARE-MS II trial. The rate of patients without clinical or radiological disease activity after 2 years was 32% with alemtuzumab. aHSCT trial data on absence of disease activity show NEDA rates between 70 and 90% after 2 years. Here we assume 40% and 80% after 2 years for the ocrelizumab/alemtuzumab and aHSCT groups, respectively.
For all three treatments, a potential long-term benefit has to be balanced with potentially harmful treatment related risks. A randomised controlled trial offers the opportunity to gain further information about efficacy and safety of all treatments and will give new insights into the immunology of high active RRMS.
- Conditions
- Relapsing-Remitting Multiple Sclerosis
- Being tested
- Autologous Hematopoietic Stem Cell Transplantation, Ocrelizumab, Alemtuzumab
- Keywords
- autologous hematopoetic stem cell transplantation, alemtzumab, ocrelizumab, randomised controlled trial, aggressive highly active multiple sclerosis, no evidence of diseae activity (NEDA)
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Hematopoietic Stem Cell TransplantationDrug
Autologous Hematopoietic Stem Cell Transplantation
OcrelizumabDrug
600 mg every 6 months continuously
AlemtuzumabDrug
12 mg/day for 5 consecutive days and again after 365 days for 3 days
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Drug: Ocrelizumab; Drug: Alemtuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: through study completion, on average at least 2 years
Secondary outcomes (9)
Efficacy of treatment defined by EDSS
EDSS change and EDSS improvement will be considered. EDSS improvement defined as confirmed improvement after 3 months
Measured: through study completion, on average at least 2 years
Efficacy of treatment defined by the annualized relapse rate
calculated as number of relapses per year
Measured: through study completion, on average at least 2 years
Efficacy of treatment defined by the number of new T2 lesions
calculated as cumulative number of new T2 lesions
Measured: through study completion, on average at least 2 years
Efficacy of treatment defined by the number of Gd-enhancing lesions
calculated as cumulative number of GD-enhancing lesions
Measured: through study completion, on average at least 2 years
Efficacy of treatment defined by multiple sclerosis functional composite (MSFC) change
based on summed up Z-scores for individual measures (SDMT, 9 HPT, 25 FWT)
Measured: through study completion, on average at least 2 years
Efficacy of treatment defined by Hamburg quality of life scale in MS (HAQUAMS)
based on HAQUAMS sum score ratings (values between 1 and 5)
Measured: through study completion, on average at least 2 years
Efficacy of treatment defined by the Percentage Brain Volume Change (PBVC)
Brain tissue volume (grey matter, white matter) will be evaluated on T1 weighted images to compute absolute percentage brain volume change
Measured: through study completion, on average at least 2 years
Efficacy of treatment defined by grey and white matter atrophy
based on grey and white matter volume change evaluated on T1 weighted images
Measured: through study completion, on average at least 2 years
Rate of AE / SAE including NCI grade 3 and 4 non-haematological toxicities
Safety of treatment defined by the rate of AE / SAE including NCI grade 3 and 4 non-haematological toxicities
Measured: through study completion, on average at least 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2021
- Study start27 Aug 2021
- Primary completion4 Feb 2022
- Study completion4 Feb 2022
Why it stopped: Lack of recruitment due to low acceptance of the control arm.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsing-Remitting Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Universitätsklinikum Hamburg-EppendorfThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomised to control (ocrelizumab or alemtuzumab) or intervention (aHSCT).
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitätsklinikum Hamburg-Eppendorf
- Sponsor type
- University, hospital or other
- Collaborators
- Neovii Biotech, Clinical Trial Center North (CTC North GmbH & Co. KG)
- Responsible party
- Sponsor
- Investigators
- Nicolaus Kröger, Prof. Dr., Principal investigator, University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04971005
- Sponsor's protocol ID
- inims-009
- Acronym
- COAST
- Status last verified
- Mar 2022
- First submitted
- 12 Aug 2020
- Last updated
- 16 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Trial to Compare Ocrelizumab or Alemtuzumab With Autologous Hematopoietic Stem Cell Transplantation (aHSCT) in High Inflammatory Multiple Sclerosis (COAST)
- ClinicalTrials.gov ID
- NCT04971005
- Acronym / sponsor ID
- COAST / inims-009
- 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)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of recruitment due to low acceptance of the control arm.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Universitätsklinikum Hamburg-EppendorfUniversity, hospital or other
- Collaborators
- Neovii Biotech, Clinical Trial Center North (CTC North GmbH & Co. KG)
- Study start
- 27 Aug 2021 (actual)
- Primary completion
- 4 Feb 2022 (actual)
- Study completion
- 4 Feb 2022 (actual)
- First posted
- 21 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A rater-blinded multicentre randomised controlled phase II trial to compare the efficacy and safety of ocrelizumab or alemtuzumab and aHSCT. Active RRMS-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.
aHSCT appears highly efficacious in reducing inflammatory disease activity and relapses in active relapsing-remitting MS. Cohort data show a long-term stagnation of inflammatory disease activity for up to 10 years and more after aHSCT. However, efficacy data from randomised controlled trials comparing aHSCT with approved treatments are still lacking.
The best available data concerning disease activity in MS patients with a documented treatment failure are from the CARE-MS II trial. The rate of patients without clinical or radiological disease activity after 2 years was 32% with alemtuzumab. aHSCT trial data on absence of disease activity show NEDA rates between 70 and 90% after 2 years. Here we assume 40% and 80% after 2 years for the ocrelizumab/alemtuzumab and aHSCT groups, respectively.
For all three treatments, a potential long-term benefit has to be balanced with potentially harmful treatment related risks. A randomised controlled trial offers the opportunity to gain further information about efficacy and safety of all treatments and will give new insights into the immunology of high active RRMS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients will be randomised to control (ocrelizumab or alemtuzumab) or intervention (aHSCT).
| Arm | Type | Receives |
|---|---|---|
| Intervention (aHSCT) | Experimental | Drug: Autologous Hematopoietic Stem Cell TransplantationAutologous 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). |
| Control | Active comparator | Drug: Ocrelizumab, Drug: AlemtuzumabIn 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). |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous Hematopoietic Stem Cell TransplantationAutologous Hematopoietic Stem Cell Transplantation | Drug | Intervention (aHSCT) |
| Ocrelizumab600 mg every 6 months continuously | Drug | Control |
| Alemtuzumab12 mg/day for 5 consecutive days and again after 365 days for 3 days | Drug | Control |
Primary outcome
Time to treatment failure as assessed by failure of NEDA (no evidence of disease activity)
Time frame: through study completion, on average at least 2 years
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
9 secondary outcomes
Efficacy of treatment defined by EDSS
Time frame: through study completion, on average at least 2 years
Efficacy of treatment defined by the annualized relapse rate
Time frame: through study completion, on average at least 2 years
Efficacy of treatment defined by the number of new T2 lesions
Time frame: through study completion, on average at least 2 years
Efficacy of treatment defined by the number of Gd-enhancing lesions
Time frame: through study completion, on average at least 2 years
Efficacy of treatment defined by multiple sclerosis functional composite (MSFC) change
Time frame: through study completion, on average at least 2 years
Efficacy of treatment defined by Hamburg quality of life scale in MS (HAQUAMS)
Time frame: through study completion, on average at least 2 years
Efficacy of treatment defined by the Percentage Brain Volume Change (PBVC)
Time frame: through study completion, on average at least 2 years
Efficacy of treatment defined by grey and white matter atrophy
Time frame: through study completion, on average at least 2 years
Rate of AE / SAE including NCI grade 3 and 4 non-haematological toxicities
Time frame: through study completion, on average at least 2 years
Results and safety
The study was stopped early (reason given: Lack of recruitment due to low acceptance of the control arm.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicolaus Kröger, Prof. Dr. principal investigator
University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Autologous Hematopoietic Stem Cell Transplantation, Ocrelizumab and Alemtuzumab in people with Relapsing-Remitting Multiple Sclerosis, run by Universitätsklinikum Hamburg-Eppendorf at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of recruitment due to low acceptance of the control arm.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to treatment failure as assessed by failure of NEDA (no evidence of disease activity) (time frame: through study completion, on average at least 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2022.