Stroke, AcutePhase 2/3TREASURENCT02961504
Treatment Evaluation of Acute Stroke for Using in Regenerative Cell Elements
A Phase 2/3 study testing HLCM051 in people with Stroke, Acute, run by Healios K.K. at 1 site in Japan.
Trial summary
The primary objectives of this study is to evaluate the efficacy of HLCM051 on functional outcome in subjects with acute ischemic stroke and to evaluate the safety of HLCM051 in subjects with acute ischemic stroke. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Stroke, Acute
- What is being tested?
- HLCM051
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 206 participants
- Where
- 1 siteJapan
- Study dates
- 15 Nov 2017to 28 Feb 2023
- Phase
- Phase 2/3
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Japanese male or female patients 20 years of age or older;
- Clinical diagnosis of cerebral cortical ischemic stroke;
- Occurrence of an ischemic stroke with clear motor or speech deficit documented by National Institutes of Health Stroke Scale (NIHSS) score of 8 to 20 (at the baseline assessment) that did not change by ≥4 points from the screening to the baseline assessment;
- Onset of ischemic stroke must have occurred within 18 to 36 hours prior to the start of administration of the investigational product;
- Confirmation of hemispheric cortical infarct with brain magnetic resonance imaging (MRI) including diffusion-weighted imaging with b-value of 1,000 demonstrating an acute lesion measuring ≥ 2.0 cm of longest diameter;
- A modified Rankin Scale (mRS) of 0 or 1, by either self-report or family report, prior to the onset of ischemic stroke;
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- Female patients who meet either:
- Not pregnant, not breastfeeding/ interrupting breastfeeding, and not planning on becoming pregnant during the trial;
- Not of childbearing potential, defined as one who has been postmenopausal for at least 1 year, or has been surgically sterilized, or has had a hysterectomy at least 3 months prior to the start of this trial; or
- If of childbearing potential, one who has agreed to follow investigator's advice and use an effective contraceptive method up to the end of the trial. Effective contraceptive methods include contraceptive methods used consistently and correctly (oral contraceptives, intrauterine devices, diaphragm, or male or female condoms), abstinence, and a sterile sexual partner;
- Male patients with female partners of childbearing potential must agree to follow investigator's advice and use adequate contraceptive methods (a combination of a condom and another form of contraception) up to the end of the trial if engaging in sexual intercourse;
- Patients or legal representatives must freely sign the informed consent form after the nature of the trial and the disclosure of his/her data have been explained;
- Willing and able to comply with all aspects of the treatment and testing schedule; and
- Willing and able to return to the trial site for the post-treatment evaluations.
Who cannot join
- Presence of a lacunar, a lesion of ≤ 2.0 cm of longest diameter, or a brainstem infarct on MRI as the etiology of symptoms of ischemic stroke;
- Reduced level of consciousness (score of 3 for item 1a of NIHSS);
- Occurrence of a hemorrhagic transformation as evidenced by computerized tomography (CT) or brain MRI scan that is clinically significant in the opinion of the investigator;
- Ipsilateral focal neurological deficits from prior lesions in the brain that would complicate evaluation;
- Experienced seizures since the onset of ischemic stroke;
- History of a neurological event such as stroke or clinically significant head trauma within 6 months prior to the start of screening;
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- Patients who both received tPA treatment and underwent mechanical reperfusion (patients are eligible for the trial if they had only one of them, tPA treatment or mechanical reperfusion);
- Uncontrolled hypertension, defined as persistent systolic blood pressure >220 mmHg or diastolic blood pressure >120 mmHg, despite antihypertensive therapy;
- Blood glucose level <50 mg/dL or >350 mg/dL at baseline;
- Patients who have a significant comorbid medical condition(s), including, but not limited to:
- Severe kidney disease requiring hemodialysis or peritoneal dialysis;
- Advanced liver disease such as hepatitis or liver cirrhosis;
- Severe congestive heart failure or history of ejection fraction <30%;
- Severe lung disease requiring home oxygen; or
- Active unstable angina requiring daily treatment with nitrates or other medications;
- Known human immunodeficiency virus infection, ongoing systemic infection, severe local infection or who are immunocompromised;
- Alzheimer's disease or other dementias, Parkinson's disease, or any other neurological disorder that in the opinion of the trial doctor would affect their ability to participate in the trial or confound study assessments;
- History of malignant tumor(s) within 2 years of the onset of ischemic stroke, with the exception of adequately treated basal or squamous cell carcinoma of the skin;
- Contraindication for MRI such as implanted pacemakers or other metallic prosthesis incompatible with MRI, body weight, or claustrophobia;
- Thrombocytopenia (platelet count <100,000/mm3) or heparin-induced thrombocytopenia;
- Known allergy to human tissue or bovine or porcine products, or religious objections to biological products;
- Prior participation in another clinical trial involving investigational pharmacological agents or devices within 30 days prior to providing consent to receive the investigational product, or participation in investigational pharmacological agents, devices, or rehabilitation stroke recovery program is planned during the trial;
- Other serious medical or psychiatric illness that is not adequately controlled and, in the investigator's opinion, would not permit the subject to be managed according to the protocol;
- Previous surgical removal of the spleen;
- Major fluctuation in neurological status since the onset of ischemic stroke indicating progression or expansion of ischemic stroke, or possible transient ischemic attack;
- Plan to have a neurovascular procedure (e.g., carotid endarterectomy, stent placement, etc.) within the first year following ischemic stroke; or
- Abnormal laboratory test results which investigators consider clinically significant and inappropriate for the trial.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Placebo-Controlled, Double-Blind, Phase 2/3 Efficacy and Safety Trial of HLCM051 (MultiStem®) in Patients With Ischemic Stroke
The primary objectives of this study is to evaluate the efficacy of HLCM051 on functional outcome in subjects with acute ischemic stroke and to evaluate the safety of HLCM051 in subjects with acute ischemic stroke.
Read the detailed description
This is a randomized, placebo-controlled, double-blind, multicenter, phase 2/3 trial to evaluate the efficacy and safety of intravenous administration of HLCM051 compared with placebo in subjects with acute ischemic stroke (within 36 hours of onset). Japanese subjects who developed a subcortical ischemic stroke and are eligible to participate in the trial will be evaluated.
Approximately 220 subjects will be randomized in a 1:1 ratio (HLCM051 group [n=110] or placebo group [n=110]) to receive a single infusion of HLCM051 or placebo.
- Conditions
- Stroke, Acute
- Being tested
- HLCM051, Placebo
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HLCM051Biological
Within 18 to 36 hours after the onset of ischemic stroke, subjects will receive a single dose of 1.2 billion HLCM051 cells to be intravenously administered
PlaceboBiological
Within 18 to 36 hours after the onset of ischemic stroke, subjects will receive a single dose of placebo to be intravenously administered
| Study group | Role | What they receive |
|---|---|---|
| HLCM051 (MultiStem) | Experimental | single dose of 1.2 billion HLCM051 cells Receives: Biological: HLCM051 |
| Placebo | Placebo comparator | a single dose of placebo Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects with an excellent outcome defined by the functional assessments
<Excellent outcome> is defined as mRS score of ≤1 (scale, 0 to 6), NIHSS score of ≤1 (scale, 0 to 42), and BI score of ≥95 (scale, 0 to 100).
Measured: Day 90
Comparison between the HLCM051 and the placebo groups in key adverse events
Measured: within Day90
Secondary outcomes (12)
Proportion of subjects with an excellent outcome defined by the functional assessments
Measured: Day 365
Proportion of subjects exhibiting functional outcome throughout the range of mRS scores by shift analysis
Measured: Day 90
Proportion of subjects exhibiting functional outcome throughout the range of mRS scores by shift analysis
Measured: Day 365
Proportion of subjects who meet all of a mRS score of ≤2, NIHSS score improvement of ≥75% from baseline and a BI score of ≥95
Measured: Day 90
Proportion of subjects with a mRS score of ≤1 and a mRS score of ≤2
Measured: Day 90
Proportion of subjects with a NIHSS score of ≤1
Measured: Day 90
Proportion of subjects with a favorable outcome (NIHSS score improvement of ≥75% from baseline) in neurological symptoms
Measured: Day 90
Proportion of subjects with a BI score of ≥95
Measured: Day 90
Proportion of subjects who survived without life-threatening adverse events (AEs)
Measured: Day 90
Proportion of subjects who survived without secondary infections
Measured: Day 90
Global recovery (i.e., GEE) and dichotomous assessment
Global recovery is an integrated assessment of patients who meet all of mRS score of ≤2, NIHSS score improvement of ≥75% from baseline, and BI score of ≥95, survival without life-threatening AEs and secondary infections
Measured: Day 90
Comparison of the incidence of secondary infections (local and systemic), AEs, death, vital signs and laboratory parameters between the HLCM051 and the placebo groups
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2016 (estimated)
- Study start15 Nov 2017
- Primary completion31 Mar 2021
- Study completion28 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Stroke, AcuteStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 206 participants (actual)
Sponsor and investigators
- Lead sponsor
- Healios K.K.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02961504
- Sponsor's protocol ID
- B01-03
- Acronym
- TREASURE
- Status last verified
- Jan 2024
- First submitted
- 7 Nov 2016
- Last updated
- 17 Jan 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Houkin K, Osanai T, Uchiyama S, Minematsu K, Taguchi A, Maruichi K, Niiya Y, Asaoka K, Kuga Y, Takizawa K, Haraguchi K, Yoshimura S, Kimura K, Tokunaga K, Aoyama A, Ikawa F, Inenaga C, Abe T, Tominaga A, Takahashi S, Kudo K, Fujimura M, Sugiyama T, Ito M, Kawabori M, Hess DC, Savitz SI, Hirano T; TREASURE Study Investigators. Allogeneic Stem Cell Therapy for Acute Ischemic Stroke: The Phase 2/3 TREASURE Randomized Clinical Trial. JAMA Neurol. 2024 Feb 1;81(2):154-162. doi: 10.1001/jamaneurol.2023.5200.
PubMed 38227308Osanai T, Houkin K, Uchiyama S, Minematsu K, Taguchi A, Terasaka S. Treatment evaluation of acute stroke for using in regenerative cell elements (TREASURE) trial: Rationale and design. Int J Stroke. 2018 Jun;13(4):444-448. doi: 10.1177/1747493017743057. Epub 2017 Nov 14.
PubMed 29134924
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Placebo-Controlled, Double-Blind, Phase 2/3 Efficacy and Safety Trial of HLCM051 (MultiStem®) in Patients With Ischemic Stroke
- ClinicalTrials.gov ID
- NCT02961504
- Acronym / sponsor ID
- TREASURE / B01-03
- Conditions
- Stroke, Acute
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 206 participants (actual)
- Lead sponsor
- Healios K.K.Industry (pharma, biotech, devices)
- Study start
- 15 Nov 2017 (actual)
- Primary completion
- 31 Mar 2021 (actual)
- Study completion
- 28 Feb 2023 (actual)
- First posted
- 11 Nov 2016 (estimated)
- 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.
The primary objectives of this study is to evaluate the efficacy of HLCM051 on functional outcome in subjects with acute ischemic stroke and to evaluate the safety of HLCM051 in subjects with acute ischemic stroke.
Detailed description
This is a randomized, placebo-controlled, double-blind, multicenter, phase 2/3 trial to evaluate the efficacy and safety of intravenous administration of HLCM051 compared with placebo in subjects with acute ischemic stroke (within 36 hours of onset). Japanese subjects who developed a subcortical ischemic stroke and are eligible to participate in the trial will be evaluated.
Approximately 220 subjects will be randomized in a 1:1 ratio (HLCM051 group [n=110] or placebo group [n=110]) to receive a single infusion of HLCM051 or placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HLCM051 (MultiStem) | Experimental | Biological: HLCM051single dose of 1.2 billion HLCM051 cells |
| Placebo | Placebo comparator | Biological: Placeboa single dose of placebo |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Japanese male or female patients 20 years of age or older;
- Clinical diagnosis of cerebral cortical ischemic stroke;
- Occurrence of an ischemic stroke with clear motor or speech deficit documented by National Institutes of Health Stroke Scale (NIHSS) score of 8 to 20 (at the baseline assessment) that did not change by ≥4 points from the screening to the baseline assessment;
- Onset of ischemic stroke must have occurred within 18 to 36 hours prior to the start of administration of the investigational product;
- Confirmation of hemispheric cortical infarct with brain magnetic resonance imaging (MRI) including diffusion-weighted imaging with b-value of 1,000 demonstrating an acute lesion measuring ≥ 2.0 cm of longest diameter;
Key exclusion criteria (27 listed)
- Presence of a lacunar, a lesion of ≤ 2.0 cm of longest diameter, or a brainstem infarct on MRI as the etiology of symptoms of ischemic stroke;
- Reduced level of consciousness (score of 3 for item 1a of NIHSS);
- Occurrence of a hemorrhagic transformation as evidenced by computerized tomography (CT) or brain MRI scan that is clinically significant in the opinion of the investigator;
- Ipsilateral focal neurological deficits from prior lesions in the brain that would complicate evaluation;
- Experienced seizures since the onset of ischemic stroke;
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 |
|---|---|---|
| HLCM051Within 18 to 36 hours after the onset of ischemic stroke, subjects will receive a single dose of 1.2 billion HLCM051 cells to be intravenously administered | Biological | HLCM051 (MultiStem) |
| PlaceboWithin 18 to 36 hours after the onset of ischemic stroke, subjects will receive a single dose of placebo to be intravenously administered | Biological | Placebo |
Primary outcome
Proportion of subjects with an excellent outcome defined by the functional assessments
Time frame: Day 90
<Excellent outcome> is defined as mRS score of ≤1 (scale, 0 to 6), NIHSS score of ≤1 (scale, 0 to 42), and BI score of ≥95 (scale, 0 to 100).
Comparison between the HLCM051 and the placebo groups in key adverse events
Time frame: within Day90
12 secondary outcomes
Proportion of subjects with an excellent outcome defined by the functional assessments
Time frame: Day 365
Proportion of subjects exhibiting functional outcome throughout the range of mRS scores by shift analysis
Time frame: Day 90
Proportion of subjects exhibiting functional outcome throughout the range of mRS scores by shift analysis
Time frame: Day 365
Proportion of subjects who meet all of a mRS score of ≤2, NIHSS score improvement of ≥75% from baseline and a BI score of ≥95
Time frame: Day 90
Proportion of subjects with a mRS score of ≤1 and a mRS score of ≤2
Time frame: Day 90
Proportion of subjects with a NIHSS score of ≤1
Time frame: Day 90
Proportion of subjects with a favorable outcome (NIHSS score improvement of ≥75% from baseline) in neurological symptoms
Time frame: Day 90
Proportion of subjects with a BI score of ≥95
Time frame: Day 90
Proportion of subjects who survived without life-threatening adverse events (AEs)
Time frame: Day 90
Proportion of subjects who survived without secondary infections
Time frame: Day 90
Global recovery (i.e., GEE) and dichotomous assessment
Time frame: Day 90
Comparison of the incidence of secondary infections (local and systemic), AEs, death, vital signs and laboratory parameters between the HLCM051 and the placebo groups
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2024.
- Derived from this study: PubMed 38227308Houkin K, Osanai T, Uchiyama S, Minematsu K, Taguchi A, Maruichi K, Niiya Y, Asaoka K, Kuga Y, Takizawa K, Haraguchi K, Yoshimura S, Kimura K, Tokunaga K, Aoyama A, Ikawa F, Inenaga C, Abe T, Tominaga A, Takahashi S, Kudo K, Fujimura M, Sugiyama T, Ito M, Kawabori M, Hess DC, Savitz SI, Hirano T; TREASURE Study Investigators. Allogeneic Stem Cell Therapy for Acute Ischemic Stroke: The Phase 2/3 TREASURE Randomized Clinical Trial. JAMA Neurol. 2024 Feb 1;81(2):154-162. doi: 10.1001/jamaneurol.2023.5200.
- Derived from this study: PubMed 29134924Osanai T, Houkin K, Uchiyama S, Minematsu K, Taguchi A, Terasaka S. Treatment evaluation of acute stroke for using in regenerative cell elements (TREASURE) trial: Rationale and design. Int J Stroke. 2018 Jun;13(4):444-448. doi: 10.1177/1747493017743057. Epub 2017 Nov 14.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing HLCM051 in people with Stroke, Acute, run by Healios K.K. at 1 site in Japan.
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 14 inclusion and 27 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: finished, as of the sponsor's last update on 17 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Proportion of subjects with an excellent outcome defined by the functional assessments (time frame: Day 90). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02961504, which also lists 2 linked publications.
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 17 Jan 2024.