StrokePhase 2NCT01273337
Study of ALD-401 Via Intracarotid Infusion in Ischemic Stroke Subjects
A Phase 2 study testing ALD-401 in people with Stroke and Ischemic Stroke, run by Aldagen at 9 sites in United States.
Trial summary
The purpose of this study is to demonstrate the safety of the delivery of ALD-401 by intracarotid infusion and to assess efficacy of treatment in subjects who have had unilateral, predominately cortical, ischemic strokes in the middle cerebral artery (MCA). Read more about this study
- Who is it for?
- Ages 30 to 83 years
- Conditions the study is for
- Stroke, Ischemic Stroke, Stroke in Middle Cerebral Artery (MCA)
- What is being tested?
- ALD-401
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 9 sitesUnited States
- Study dates
- Mar 2011to Jan 2015
- 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 30 to 83 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Is age 30 to 83 years,
- Has recent acute ischemic stroke in the middle cerebral artery (MCA) distribution confirmed by MRI or CT scan, with known onset time (within 24 hr),
- Has persistent neurological deficit (NIHSS ≤22), mRS ≥ 3 at randomization,
- Is able to provide bone marrow sample from anterior or posterior iliac crest at the time required by targeted infusion date,
- Is able to return for dosing two days post bone marrow harvest (day 13-19 post stroke) and remain overnight for observation,
- Is able to undergo (no contraindications) catheterization for localizing arteriograms for intracarotid/MCA delivery,
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- Has patency of the carotid artery on the affected side demonstrated at screening and prior to infusion; and flow is established in the proximal branches (M1 and M2) of the affected carotid if the stroke is cortical. Occlusion of either the M1 or M2 can be included in the study if imaging prior to harvest demonstrates flow through collateral circulation to the area of the infarct. If the infarction is lacunar, the proximal MCA must be patent,
- Subjects who received tPA or underwent mechanical reperfusion may be included in the study as long as flow is established either in the proximal branches (M1 and M2) of the affected carotid or in the collateral circulation to the area of the infarct,
- Has a general state that is compatible with a program of functional rehabilitation, and is receiving standard of care as determined by the investigator,
- Is able to provide consent to study or informed consent is obtained from the subject's next of kin or legal representative,
- Females must be postmenopausal, surgically sterilized, or practicing a suitable method of birth control so that, in the opinion of the investigator, they will not become pregnant during the course of the study,
- Is a good candidate for the trial, in the opinion of the investigator.
Who cannot join
- Medical Conditions:
- Has a medical history of neurological or orthopedic pathology with deficit as a consequence that results in a modified Rankin Scale score >1 before stroke) or has a cognitive deficit,
- Has a severe, persistent neurological deficit (NIHSS >22), OR a change of ≥4 points in the NIHSS from screening (after 7 days) to randomization (3-4 days after screening),
- Has any clinically significant hemorrhagic (HI1 or PH1 petechial hemorrhages are allowed), or traumatic lesion of the brain on MRI or CT,
- Has stroke affecting the sub cortical area only,
- Has >50% stenosis or ulcerated plaque in the carotid artery on the ipsilateral side and carotid endarterectomy or arterial stenting is recommended for treatment,
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- Has had a seizure in the past 6 months (including associated with stroke),
- Has a serious psychiatric disease which could alter evaluation on functional or cognitive scales,
- Has a serious neurologic disease (e.g., multiple sclerosis, ALS) which could alter evaluation on functional or cognitive scales,
- Had a myocardial infarction in the past 3 months,
- Has a mechanical heart valve,
- Has a history of ischemic stroke in any distribution within one month of the date of onset of the qualifying stroke for inclusion into this study,
- Has known hepatic failure (Child-Pugh score Class B or C),
- Has an active systemic infection,
- Has an active malignancy or diagnosis of malignancy within 5 years prior to the start of screening (excluding skin cancers other than melanoma) or any history of chemotherapy or radiation affecting the bone marrow,
- Has a history of inflammatory or progressively fibrotic conditions (e.g., rheumatoid arthritis, systemic lupus erythematosis, vasculitic disorders, idiopathic pulmonary fibrosis, retroperitoneal fibrosis),
- Has another comorbid disease, including cardiovascular disease, which would be expected to result in less than 6-months life expectancy,
- Has any concurrent illness or condition that in the opinion of the investigator might interfere with treatment or evaluation of safety and/or efficacy,
- Has current or recent history of alcohol or drug abuse, or stroke considered associated with drug abuse.
- Laboratory Findings:
- Hemoglobin <10 g/dl,
- Uncorrected coagulopathy as defined as INR >1.4; PTT >35 sec,
- Platelet counts of <100,000 or >700,000,
- Any hemodynamic instability at the time of consent (e.g., requiring continuous fluid resuscitation or ionotropic support), or hypoxemia (oxygen saturation of < 90%) on supplemental oxygen more than FIO2 = 0.3,
- Renal insufficiency (creatinine clearance of < 50 mL/min/m2).
- Poorly controlled diabetes mellitus (HbA1c > 10%),
- Hypertension with SBP ≥ 150 mmHg or DBP ≥ 95 mmHg despite adequate anti-hypertensive treatment (at any measurement within 3 days of randomization).
- Concomitant or Prior Therapies:
- Subjects receiving systemic anticoagulation with warfarin, heparin or heparin analogs (patients on antiplatelet agents, including aspirin, or on prophylactic anticoagulation may enroll at the investigator's and proceduralists' discretion) and if exclusion 2b is not met,
- Subjects currently receiving immunosuppressant drugs (e.g., for treatment of organ transplants, psoriasis, Crohn's disease, alopecia areata),
- Subjects currently receiving restricted concomitant medications,
- Any previous or current treatment with angiogenic growth factors, cytokines, gene therapy or stem cell therapy,
- Currently receiving anti-angiogenic drugs,
- Subjects participating in another clinical trial of an investigational therapy (including placebo) within 30 days of the start of screening.
- Other:
- Pregnant or nursing women (women capable of childbearing must have a negative serum pregnancy test at screening),
- Is unable to return for follow up visits for clinical evaluation, safety evaluation, laboratory studies, or MRI or CT evaluation,
- Is unable to undergo MRI or CT,
- Has allergies to local or general anesthetics, or contrast media.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
University Medical Center at Brackenridge
Austin, Texas, 78701
Ohio Health Research Institute
Columbus, Ohio, 43214
Duke University Medical Center
Durham, North Carolina, 27710
The University of Texas Medical School
Houston, Texas, 77030
Los Angeles Brain and Spine Institute
Los Angeles, California, 90027
University of Miami Hospital
Miami, Florida, 33136
Minneapolis Heart Institute
Minneapolis, Minnesota, 55407
University of Pittsburgh Medical Center Presbyterian Hospital
Pittsburgh, Pennsylvania, 15213
Swedish Medical Center, Cherry Hill Campus
Seattle, Washington, 98122
About this study
Official title: A Phase 2 Randomized, Controlled Study With a Phase 1 Safety Cohort Testing ALD-401 Derived From Autologous Bone Marrow Delivered Via Intracarotid Infusion in Subjects With Ischemic Stroke With Blinded Assessments
The purpose of this study is to demonstrate the safety of the delivery of ALD-401 by intracarotid infusion and to assess efficacy of treatment in subjects who have had unilateral, predominately cortical, ischemic strokes in the middle cerebral artery (MCA). ALD-401 is made from the stroke patient's bone marrow and infused 13-19 days after the stroke.
Read the detailed description
This is a randomized, sham-controlled, multi-center, parallel-group, study in male and female subjects, designed to determine the safety and efficacy of ALD-401 in treating primary ischemic stroke. Approximately 100 subjects will be randomized 3:2 within a site to the treatment or sham control arm. Subjects experiencing an ischemic stroke will undergo either a bone marrow or a sham harvest on days 11-17 and be dosed with ALD-401 or a sham procedure 13-19 days after the primary event. Bone marrow cells are processed, sorted and formulated into a 3 mL suspension of ALD-401. Two days after harvest, subjects in the ALD-401 group will have their processed bone marrow cells (ALD-401) injected via intracarotid/MCA infusion, while control subjects have a sham infusion. All subjects will be followed for 12 months to monitor safety and to assess mental and physical function.
This study seeks to demonstrate safety of ALD-401 derived from autologous bone marrow and given via intracarotid delivery in a therapeutic window of 13-19 days post primary stroke event. This dosing window was selected to allow post-stroke inflammatory response to recede and therefore minimize the impact of resident inflammatory cells on the administration of ALD-401. This dosing window was consistent with information derived from pre-clinical models. Intracarotid/MCA delivery may offer minimal loss or dilution of therapeutic cells prior to localization in and around the ischemic area of the brain. ALD-401 will be manufactured from the patient's own bone marrow harvested 11-17 days after the primary stroke event.
- Being tested
- ALD-401, Sham Procedure
- Keywords
- Stroke, Ischemia, Ischemic Stroke, Middle Cerebral Artery, MCA, Stem Cells, Stem Cell, Autologous Bone Marrow, Ipsilateral MCA
- Medical subject headings
- Stroke, Ischemic Stroke, Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALD-401Biological
Also called ALDHbr cells, ALDH Bright cells
3 mL ALDHbr cells isolated from autologous bone marrow given as a one-time infusion via intracarotid infusion.
Sham ProcedureProcedure or surgery
Sham bone marrow harvest and sham product infusion procedures.
| Study group | Role | What they receive |
|---|---|---|
| ALD-401 | Experimental | ALD-401 is derived from Autologous Bone Marrow of the Stroke Subject Receives: Biological: ALD-401 |
| Sham Comparitor | Sham comparator | Sham Bone Marrow harvest and sham dosing procedure. Receives: Procedure: Sham Procedure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of Delivery of ALD-401
The safety of the delivery of ALD-401 will be assessed by the following:
- Frequency and proportion of severe adverse events,
- Physical and clinical laboratory testing,
- Radiological worsening as detected by MRI (evidence of hemorrhage) with and without clinical symptoms,
- MRI evidence of new heterotopias, tumors, or vascular malformations over 12 months
- Increase of NIHSS by ≥ 4 pts within 24 h of injection,
- Re-hospitalization,
- Survival.
Measured: 1 year
Secondary outcomes (1)
Efficacy of recovery of Mental and Physical Function
Determine the efficacy of ALD-401 for recovery of mental and physical function three months after treatment as assessed by the:
- Modified Rankin Scale (mRS)
- NIH Stroke Scale (NIHSS)
- Barthel Index (BI)
- European Quality of Life (EQ-5D)
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 posted10 Jan 2011 (estimated)
- Study startMar 2011
- Primary completionJul 2014 (estimated)
- Study completionJan 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aldagen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- James M Hinson, MD, Study director, Aldagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01273337
- Sponsor's protocol ID
- IS-001
- Status last verified
- Jan 2014
- First submitted
- 6 Jan 2011
- Last updated
- 16 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Savitz SI, Yavagal D, Rappard G, Likosky W, Rutledge N, Graffagnino C, Alderazi Y, Elder JA, Chen PR, Budzik RF Jr, Tarrel R, Huang DY, Hinson JM Jr. A Phase 2 Randomized, Sham-Controlled Trial of Internal Carotid Artery Infusion of Autologous Bone Marrow-Derived ALD-401 Cells in Patients With Recent Stable Ischemic Stroke (RECOVER-Stroke). Circulation. 2019 Jan 8;139(2):192-205. doi: 10.1161/CIRCULATIONAHA.117.030659.
PubMed 30586746
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Randomized, Controlled Study With a Phase 1 Safety Cohort Testing ALD-401 Derived From Autologous Bone Marrow Delivered Via Intracarotid Infusion in Subjects With Ischemic Stroke With Blinded Assessments
- ClinicalTrials.gov ID
- NCT01273337
- Acronym / sponsor ID
- IS-001
- Keywords
- Stroke, Ischemia, Ischemic Stroke, Middle Cerebral Artery, MCA, Stem Cells, Stem Cell, Autologous Bone Marrow
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- AldagenIndustry (pharma, biotech, devices)
- Study start
- Mar 2011
- Primary completion
- Jul 2014 (estimated)
- Study completion
- Jan 2015 (estimated)
- First posted
- 10 Jan 2011 (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 purpose of this study is to demonstrate the safety of the delivery of ALD-401 by intracarotid infusion and to assess efficacy of treatment in subjects who have had unilateral, predominately cortical, ischemic strokes in the middle cerebral artery (MCA). ALD-401 is made from the stroke patient's bone marrow and infused 13-19 days after the stroke.
Detailed description
This is a randomized, sham-controlled, multi-center, parallel-group, study in male and female subjects, designed to determine the safety and efficacy of ALD-401 in treating primary ischemic stroke. Approximately 100 subjects will be randomized 3:2 within a site to the treatment or sham control arm. Subjects experiencing an ischemic stroke will undergo either a bone marrow or a sham harvest on days 11-17 and be dosed with ALD-401 or a sham procedure 13-19 days after the primary event. Bone marrow cells are processed, sorted and formulated into a 3 mL suspension of ALD-401. Two days after harvest, subjects in the ALD-401 group will have their processed bone marrow cells (ALD-401) injected via intracarotid/MCA infusion, while control subjects have a sham infusion. All subjects will be followed for 12 months to monitor safety and to assess mental and physical function.
This study seeks to demonstrate safety of ALD-401 derived from autologous bone marrow and given via intracarotid delivery in a therapeutic window of 13-19 days post primary stroke event. This dosing window was selected to allow post-stroke inflammatory response to recede and therefore minimize the impact of resident inflammatory cells on the administration of ALD-401. This dosing window was consistent with information derived from pre-clinical models. Intracarotid/MCA delivery may offer minimal loss or dilution of therapeutic cells prior to localization in and around the ischemic area of the brain. ALD-401 will be manufactured from the patient's own bone marrow harvested 11-17 days after the primary stroke event.
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 |
|---|---|---|
| ALD-401 | Experimental | Biological: ALD-401ALD-401 is derived from Autologous Bone Marrow of the Stroke Subject |
| Sham Comparitor | Sham comparator | Procedure: Sham ProcedureSham Bone Marrow harvest and sham dosing procedure. |
Who may qualify
- Ages
- 30 to 83 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Is age 30 to 83 years,
- Has recent acute ischemic stroke in the middle cerebral artery (MCA) distribution confirmed by MRI or CT scan, with known onset time (within 24 hr),
- Has persistent neurological deficit (NIHSS ≤22), mRS ≥ 3 at randomization,
- Is able to provide bone marrow sample from anterior or posterior iliac crest at the time required by targeted infusion date,
- Is able to return for dosing two days post bone marrow harvest (day 13-19 post stroke) and remain overnight for observation,
Key exclusion criteria (39 listed)
- Medical Conditions:
- Laboratory Findings:
- Concomitant or Prior Therapies:
- Other:
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 |
|---|---|---|
| ALD-401Also: ALDHbr cells, ALDH Bright cells3 mL ALDHbr cells isolated from autologous bone marrow given as a one-time infusion via intracarotid infusion. | Biological | ALD-401 |
| Sham ProcedureSham bone marrow harvest and sham product infusion procedures. | Procedure or surgery | Sham Comparitor |
Primary outcome
Safety of Delivery of ALD-401
Time frame: 1 year
The safety of the delivery of ALD-401 will be assessed by the following: * Frequency and proportion of severe adverse events, * Physical and clinical laboratory testing, * Radiological worsening as detected by MRI (evidence of hemorrhage) with and without clinical symptoms, * MRI evidence of new heterotopias, tumors, or vascular malformations over 12 months * Increase of NIHSS by ≥ 4 pts within 24 h of injection, * Re-hospitalization, * Survival.
1 secondary outcome
Efficacy of recovery of Mental and Physical Function
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2014.
- Derived from this study: PubMed 30586746Savitz SI, Yavagal D, Rappard G, Likosky W, Rutledge N, Graffagnino C, Alderazi Y, Elder JA, Chen PR, Budzik RF Jr, Tarrel R, Huang DY, Hinson JM Jr. A Phase 2 Randomized, Sham-Controlled Trial of Internal Carotid Artery Infusion of Autologous Bone Marrow-Derived ALD-401 Cells in Patients With Recent Stable Ischemic Stroke (RECOVER-Stroke). Circulation. 2019 Jan 8;139(2):192-205. doi: 10.1161/CIRCULATIONAHA.117.030659.
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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.
James M Hinson, MD study director
Aldagen
9 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 ALD-401 in people with Stroke and Ischemic Stroke, run by Aldagen at 9 sites in United States.
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 12 inclusion and 39 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: status not confirmed, as of the sponsor's last update on 16 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. 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 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?
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?
Safety of Delivery of ALD-401 (time frame: 1 year). 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 NCT01273337, which also lists 1 linked publication.
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 Jan 2014.