A randomised controlled trial to compare ocrelizumab or alemtuzumab with autologous hematopoietic stem cell transplantation (aHSCT) in high inflammatory multiple sclerosis (COAST)

Phase 1

• Conditions: relapsing-remitting multiple sclerosis; MedDRA version: 21.1Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2016-001166-29-DE
• Lead Sponsor: niversity Medical Centre Hamburg-Eppendorf

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-08-12
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Written informed consent and agreement to comply to study protocol
2. Age: 18-55 years
3. EDSS: 0.0 – 6.0
4. RRMS according to McDonald 20108
5. < 10 years of disease course after symptom onset
6. Active disease with one of the following treatment failures occurring not earlier than 6 months after initiation of an approved DMT:
- 2 or more relapses within the last 12 months
or
- 1 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
or
- On-going signs of MRI activity in the last 6 months (either Gd-enhancing of = 3 mm lesion at any exam in the last year; or more than 5 new T2 lesions (= 3 mm))
or
- 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 failure prior to natalizumab is documented
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Secondary or primary progressive MS
2. Pregnancy, or other medical condition incompatible with aHSCT
3. Any treatment or medical condition that, according to the haematologist / transplant specialist precludes the use of aHSCT
4. John Cunningham virus (JCV) antibody index of > 1.5 in previously natalizumab-treated patients, if a negative CSF JCV-PCR prior to screening is not available
5. Relapse during 30 days before initiation of treatment. If a relapse occurs during this period and eligibility criteria are otherwise fulfilled, start of treatment will be delayed until at least 30 days after receiving steroids.
6. Concurrent clinically significant (as determined by the investigators and haematologist / transplant specialist) cardiac, immunological, pulmonary, neurological, renal or other major disease such as:
- Prominent cardial disease (Left ventricular ejection fraction (LVEF) < 40%, myocardial infarction or ischemia, uncontrolled arrhythmias, pericardial effusions > 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 positive 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
7. Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the patient returning for follow-up visits on schedule. Unwillingness to use contraception.
8. Previous participation in this study, previous treatment with aHSCT or already both comparators
9. Ongoing immunotherapy. Treatment with interferon or glatirameracetate will need no wash-out. Treatment pause before ocrelizumab/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 cholestyramine
- for cladribine: 24 weeks
10. 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 considered part of routine patient care.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified