Sickle Cell DiseasePhase 1NCT05618301
Motixafortide and Natalizumab to Mobilize CD34+ Hematopoietic Stem Cells for Gene Therapies in Sickle Cell Disease (SCD)
A Phase 1 study testing Motixafortide, Natalizumab and Leukapheresis in people with Sickle Cell Disease, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Hematopoietic stem cell (HSC)-based gene therapies now offer curative potential for patients with sickle cell disease (SCD), with decreased toxicity compared to allogeneic hematopoietic cell transplantation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Motixafortide, Natalizumab and Leukapheresis
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Jul 2023to 24 Jun 2025
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients at least 18 years old
- Diagnosis of sickle cell disease (hemoglobin SS or Sβ0 genotype)
- Receiving automated RBC exchanges via apheresis-capable central venous access or willing to have apheresis-capable venous access placed.
- Able to hold hydroxyurea, voxelotor, and/or crizanlizumab for at least 60 days prior to mobilization
- Able to hold iron chelation for at least 7 days prior to mobilization
- ECOG performance status ≤ 1
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- Normal bone marrow and organ function at screening as defined below:
- Leukocytes ≥ 2,000/uL
- Absolute neutrophil count ≥ 1,500/uL
- Platelets ≥ 75,000/uL
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN at time of screening
- Creatinine clearance ≥ 30 mL/min by Cockcroft-Gault
- Baseline oxygen saturation ≥ 92% on room air
- Left ventricular ejection fraction (LVEF) ≥ 45% (Of note, transthoracic echocardiogram (TTE) will not be required for study. However, if the treating physician has clinical concerns for active cardiac disease for which a TTE is clinically warranted as standard of care, then an EF of ≥ 45% will be required).
- The effects of motixafortide and natalizumab on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation, and 3 months after completion of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and 3 months after completion of the study.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Who cannot join
- Patients may not have a history of receiving the following therapies: prior HCT or prior gene therapy
- Currently receiving concomitant immunosuppressants including 6-mercaptopurine, azathioprine, cyclosporine, methotrexate or concomitant inhibitors of TNF-α.
- Patient may not have a history of significant alloantibodies which, in the opinion of the treating physician and study investigator, significantly increase the risk of participation in this clinical trial.
- Currently receiving any other investigational agents.
- A history of progressive multifocal leukoencephalopathy
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to motixafortide or natalizumab.
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- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (including but not limited to HIV, active/untreated Hepatitis C and/or active/untreated Hepatitis B), ongoing/active vaso-occlusive pain crisis or uncontrolled SCD-related symptoms, symptomatic congestive heart failure, cerebrovascular accident, unstable angina pectoris, or cardiac arrhythmia.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum/urine pregnancy test within 7 days of study entry and prior to each study agent administration/HSC mobilization.
- Determined by the investigator to be unable or unlikely to comply with the study procedures included in this protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Pilot Safety and Feasibility Study to Evaluate Motixafortide (CXCR4/SDF-1 Inhibition) and Natalizumab (VLA-4/VCAM-1 Inhibition) as a Novel Regimen to Mobilize CD34+ Hematopoietic Stem Cells for Gene Therapies in Sickle Cell Disease (SCD)
Hematopoietic stem cell (HSC)-based gene therapies now offer curative potential for patients with sickle cell disease (SCD), with decreased toxicity compared to allogeneic hematopoietic cell transplantation. However, effective HSC-based gene therapy depends on collecting sufficient HSCs to generate the therapeutic product, and currently available mobilization regimens carry unacceptable risk for patients with SCD or do not reliably yield optimal numbers of HSCs for gene therapy.
The investigators hypothesize that HSC mobilization with motixafortide (CXCR4i) alone and the combination of motixafortide plus natalizumab (VLA-4i) will be safe and tolerable in SCD patients. In addition, the investigators hypothesize that combined CXCR4 and VLA-4 blockade with motixafortide plus natalizumab will result in a rapid, robust, and synergistic increase in HSC mobilization to peripheral blood (PB) in patients with SCD, when compared to motixafortide alone.
- Conditions
- Sickle Cell Disease
- Being tested
- Motixafortide, Natalizumab, Leukapheresis
- Keywords
- sickle cell disease, gene therapy, hematopoietic stem cell mobilization, CXCR4 inhibition, VLA4 inhibition
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MotixafortideDrug
Also called BL-8040
Motixafortide is to be administered as a subcutaneous injection at a dose of 1.25 mg/kg
NatalizumabDrug
Also called Tysabri
Natalizumab will be administered as an IV infusion at a flat dose of 300 mg
LeukapheresisProcedure or surgery
Leukapheresis consisting of a 1 Blood Volume procedure
| Study group | Role | What they receive |
|---|---|---|
| Motixafortide followed by Motixafortide + Natalizumab | Experimental | * Consenting and eligible patients will receive a single subcutaneous injection of motixafortide, followed by leukapheresis. Patient will then be followed for 8 weeks for adverse event monitoring.
* Following the 8-week monitoring period, patients will receive a single IV infusion natalizumab, then approximately 32 hours later, a single subcutaneous injection of motixafortide, followed by leukapheresis. Patients will then be followed for 8 weeks for adverse event monitoring. Receives: Drug: Motixafortide; Drug: Natalizumab; Procedure: Leukapheresis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability as assessed by the incidence of dose-limiting toxicities (DLTs)
- All toxicities will be graded using NCI-CTCAE Version 5.0
- A DLT is an event occurring during the DLT period of 28 days following administration of either motixafortide and/or natalizumab that is considered to be at least possibly, probably or definitely related to study treatment by the investigator, and that meets the criteria below:
- Hematologic criteria
- Any Grade 5 adverse event
- Any Grade 4 adverse event, excluding Grade 4 hemolysis, bilirubin increase, leukocytosis, erythrocytosis, thrombocytosis, anemia, leukopenia, or febrile neutropenia
- Non-hematologic criteria
- Any Grade 4 or 5 adverse event.
- Any Grade 3 or higher arterial or venous thromboembolic event
- Any Grade 2 or 3 adverse event that does not resolve within 4 weeks; with the exception of <grade 2 injection site reactions.
Measured: Through 28 days following administration of either motixafortide and/or natalizumab (estimated to be 8 weeks and 4 days)
Secondary outcomes (5)
Number of CD34+ hematopoietic stem and progenitor cells (HSPCs) mobilized via leukapheresis per liter (L) of total volume (tV) processed following motixafortide alone and motixafortide + natalizumab
Measured: Day 2 and Day 60
Number of CD34+ hematopoietic stem and progenitor cells (HSPCs) mobilized via leukapheresis per liter (L) of adjusted volume (aV) processed, following motixafortide alone and motixafortide + natalizumab
-The adjusted volume will be calculated as the total volume (tV) processed minus the volumes processed to establish/re-establish the HSC collection interface (iV) to yield an adjusted volume (aV) (i.e. tV-iV=aV). The number of apheresis alarms along with the amount of time, flow rate and volumes processed to establish the interface will be recorded during apheresis and entered into the eCRF. Use of aV will control for the effect of any apheresis alarms; which pause the centrifuge leading to loss of the collection interface.
Measured: Day 2 and Day 60
Change in kinetics of CD34+ HSC mobilization in response to motixafortide alone and motixafortide + natalizumab in SCD patients, as assessed by CD34+ cells/ul in peripheral blood
Measured: From baseline through Day 60
Frequency of adverse events
-All adverse events will be graded using NCI-CTCAE Version 5.0
Measured: From start of treatment through 8 weeks following completion of all treatment (estimated to be 16 weeks and 4 days)
Change in peak CD34+ HSC mobilization in response to motixafortide alone and motixafortide + natalizumab in SCD patients, as assessed by CD34+ cells/ul in peripheral blood
Measured: From baseline through Day 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2022
- Study start7 Jul 2023
- Primary completion24 Jun 2025
- Study completion24 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- BioLineRx, Ltd., Biogen, Ayrmid Pharma
- Responsible party
- Sponsor
- Investigators
- Zachary Crees, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05618301
- Sponsor's protocol ID
- 202302190
- Status last verified
- Aug 2025
- First submitted
- 8 Nov 2022
- Last updated
- 11 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Safety and Feasibility Study to Evaluate Motixafortide (CXCR4/SDF-1 Inhibition) and Natalizumab (VLA-4/VCAM-1 Inhibition) as a Novel Regimen to Mobilize CD34+ Hematopoietic Stem Cells for Gene Therapies in Sickle Cell Disease (SCD)
- ClinicalTrials.gov ID
- NCT05618301
- Acronym / sponsor ID
- 202302190
- Conditions
- Sickle Cell Disease
- Keywords
- sickle cell disease, gene therapy, hematopoietic stem cell mobilization, CXCR4 inhibition, VLA4 inhibition
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- BioLineRx, Ltd., Biogen, Ayrmid Pharma
- Study start
- 7 Jul 2023 (actual)
- Primary completion
- 24 Jun 2025 (actual)
- Study completion
- 24 Jun 2025 (actual)
- First posted
- 16 Nov 2022 (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.
Hematopoietic stem cell (HSC)-based gene therapies now offer curative potential for patients with sickle cell disease (SCD), with decreased toxicity compared to allogeneic hematopoietic cell transplantation. However, effective HSC-based gene therapy depends on collecting sufficient HSCs to generate the therapeutic product, and currently available mobilization regimens carry unacceptable risk for patients with SCD or do not reliably yield optimal numbers of HSCs for gene therapy.
The investigators hypothesize that HSC mobilization with motixafortide (CXCR4i) alone and the combination of motixafortide plus natalizumab (VLA-4i) will be safe and tolerable in SCD patients. In addition, the investigators hypothesize that combined CXCR4 and VLA-4 blockade with motixafortide plus natalizumab will result in a rapid, robust, and synergistic increase in HSC mobilization to peripheral blood (PB) in patients with SCD, when compared to motixafortide alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Motixafortide followed by Motixafortide + Natalizumab | Experimental | Drug: Motixafortide, Drug: Natalizumab, Procedure: Leukapheresis* Consenting and eligible patients will receive a single subcutaneous injection of motixafortide, followed by leukapheresis. Patient will then be followed for 8 weeks for adverse event monitoring. * Following the 8-week monitoring period, patients will receive a single IV infusion natalizumab, then approximately 32 hours later, a single subcutaneous injection of motixafortide, followed by leukapheresis. Patients will then be followed for 8 weeks for adverse event monitoring. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Adult patients at least 18 years old
- Diagnosis of sickle cell disease (hemoglobin SS or Sβ0 genotype)
- Receiving automated RBC exchanges via apheresis-capable central venous access or willing to have apheresis-capable venous access placed.
- Able to hold hydroxyurea, voxelotor, and/or crizanlizumab for at least 60 days prior to mobilization
- Able to hold iron chelation for at least 7 days prior to mobilization
Key exclusion criteria (9 listed)
- Patients may not have a history of receiving the following therapies: prior HCT or prior gene therapy
- Currently receiving concomitant immunosuppressants including 6-mercaptopurine, azathioprine, cyclosporine, methotrexate or concomitant inhibitors of TNF-α.
- Patient may not have a history of significant alloantibodies which, in the opinion of the treating physician and study investigator, significantly increase the risk of participation in this clinical trial.
- Currently receiving any other investigational agents.
- A history of progressive multifocal leukoencephalopathy
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 |
|---|---|---|
| MotixafortideAlso: BL-8040Motixafortide is to be administered as a subcutaneous injection at a dose of 1.25 mg/kg | Drug | Motixafortide followed by Motixafortide + Natalizumab |
| NatalizumabAlso: TysabriNatalizumab will be administered as an IV infusion at a flat dose of 300 mg | Drug | Motixafortide followed by Motixafortide + Natalizumab |
| LeukapheresisLeukapheresis consisting of a 1 Blood Volume procedure | Procedure or surgery | Motixafortide followed by Motixafortide + Natalizumab |
Primary outcome
Safety and tolerability as assessed by the incidence of dose-limiting toxicities (DLTs)
Time frame: Through 28 days following administration of either motixafortide and/or natalizumab (estimated to be 8 weeks and 4 days)
* All toxicities will be graded using NCI-CTCAE Version 5.0 * A DLT is an event occurring during the DLT period of 28 days following administration of either motixafortide and/or natalizumab that is considered to be at least possibly, probably or definitely related to study treatment by the investigator, and that meets the criteria below: * Hematologic criteria * Any Grade 5 adverse event * Any Grade 4 adverse event, excluding Grade 4 hemolysis, bilirubin increase, leukocytosis, erythrocytosis, thrombocytosis, anemia, leukopenia, or febrile neutropenia * Non-hematologic criteria * Any Grade 4 or 5 adverse event. * Any Grade 3 or higher arterial or venous thromboembolic event * Any Grade 2 or 3 adverse event that does not resolve within 4 weeks; with the exception of <grade 2 injection site reactions.
5 secondary outcomes
Number of CD34+ hematopoietic stem and progenitor cells (HSPCs) mobilized via leukapheresis per liter (L) of total volume (tV) processed following motixafortide alone and motixafortide + natalizumab
Time frame: Day 2 and Day 60
Number of CD34+ hematopoietic stem and progenitor cells (HSPCs) mobilized via leukapheresis per liter (L) of adjusted volume (aV) processed, following motixafortide alone and motixafortide + natalizumab
Time frame: Day 2 and Day 60
Change in kinetics of CD34+ HSC mobilization in response to motixafortide alone and motixafortide + natalizumab in SCD patients, as assessed by CD34+ cells/ul in peripheral blood
Time frame: From baseline through Day 60
Frequency of adverse events
Time frame: From start of treatment through 8 weeks following completion of all treatment (estimated to be 16 weeks and 4 days)
Change in peak CD34+ HSC mobilization in response to motixafortide alone and motixafortide + natalizumab in SCD patients, as assessed by CD34+ cells/ul in peripheral blood
Time frame: From baseline through Day 60
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 11 Aug 2025.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Zachary Crees, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Motixafortide, Natalizumab and Leukapheresis in people with Sickle Cell Disease, run by Washington University School of Medicine at 1 site 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 16 inclusion and 9 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 11 Aug 2025. 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 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Safety and tolerability as assessed by the incidence of dose-limiting toxicities (DLTs) (time frame: Through 28 days following administration of either motixafortide and/or natalizumab (estimated to be 8 weeks and 4 days)). 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 11 Aug 2025.