Motixafortide for Sickle Cell Disease

Overseen By Alexis Leonard, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: St. Jude Children's Research Hospital

Must not be taking: Hydroxyurea, Experimental therapies

Disqualifiers: Recent hospitalization, Major surgery, Active infection, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called motixafortide (also known as Aphexda) to determine its safety for people with sickle cell disease (SCD). The main goal is to assess whether the drug can help collect more stem cells for potential future transplants, which could be crucial for advanced treatments. Participants will receive either one or two doses of motixafortide, depending on their enrollment time. People with severe SCD who are already on regular transfusions or involved in a transplant plan might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires participants to stop taking hydroxyurea for 30 days before the first dose of the study drug. For other medications, the protocol does not specify, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research suggests that motixafortide might be safe for people with sickle cell disease. In previous studies, participants handled motixafortide well. These studies examined how the drug increases the number of stem cells for potential transplants. Importantly, researchers found no major safety issues. However, since this is an early-phase study, gathering more information on possible side effects remains crucial. This trial will help confirm motixafortide's safety and effectiveness for sickle cell patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell disease?

Most treatments for sickle cell disease, like hydroxyurea or blood transfusions, focus on managing symptoms rather than addressing the underlying issues. Motixafortide is unique because it targets the CXCR4 receptor, a new mechanism that could enhance stem cell mobilization. Researchers are excited about this treatment since it offers the potential to improve stem cell collection, which is crucial for bone marrow transplants. This approach could lead to more effective and efficient treatment options for patients with sickle cell disease.

What evidence suggests that motixafortide might be an effective treatment for sickle cell disease?

Research shows that motixafortide can increase the number of stem cells in the blood, which is crucial for their collection. In this trial, participants will join different treatment arms to evaluate motixafortide's effectiveness. Treatment-Arm A involves a single dose of motixafortide, while Treatment-Arm B involves two daily doses. Studies have found that motixafortide results in higher and longer-lasting levels of essential cells needed for stem cell transplants compared to plerixafor. This suggests it might better prepare patients for stem cell collection. Additionally, motixafortide has few side effects, making it a potentially safer choice for patients. Overall, these findings suggest that motixafortide could be a promising treatment for improving stem cell collection in people with sickle cell disease. ^{2 3 4 6 7}

Who Is on the Research Team?

Alexis Leonard, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for individuals with sickle cell disease (SCD) or sickle cell anemia. It's designed to test if a drug called motixafortide can safely increase the number of stem cells in their blood, potentially helping future transplant treatments.

Inclusion Criteria

My liver tests are within the required range.

I have a confirmed diagnosis of sickle cell disease.

I either have a central line in place or can undergo apheresis without needing a new central line.

Exclusion Criteria

I need special blood types for transfusions and have had tests for blood cell antibodies.

My spleen is enlarged and painful.

Inability or unwillingness of research participant to hold hydroxyurea for 30 days prior to first dose of study drug

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive a single dose of motixafortide followed by stem cell collection 8 hours later

1 day

1 visit (in-person)

Treatment Part B

Participants receive two daily doses of motixafortide with stem cell collection after each dose

2 days

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

7-10 days

1 visit (in-person)

Extended Follow-up

Study staff will contact participants about 30 days after the last drug dose administration

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Motixafortide

Trial Overview The study examines the safety and effectiveness of motixafortide in increasing stem cells for collection. Participants will receive either one dose (Part A) or two doses (Part B), and researchers will track how many stem cells are mobilized.

How Is the Trial Designed?

Group I: Treatment-Arm B-Two Daily Doses Experimental Treatment 1 Intervention

Part B: Participants who enroll later in the study will be assigned to Part B. Part B participants will get two doses of the study drug and two stem cell collection processes over two days (one on each day).

Group II: Treatment-Arm A-Single Dose Experimental Treatment 1 Intervention

Part A: Participants who enroll early will be assigned to Part A. Part A participants will get one dose of the study drug and one stem cell collection process.

Motixafortide is already approved in United States for the following indications:

Approved in United States as Aphexda for:

• Multiple myeloma

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

BioLineRx, Ltd.

Industry Sponsor

Trials

24

Recruited

2,200+

Published Research Related to This Trial

In a retrospective survey of 13 haemophilia patients with inhibitors treated with recombinant factor VIIa (rFVIIa), prophylactic treatment significantly reduced the number of bleeding episodes compared to previous therapies.

Most patients reported high satisfaction with rFVIIa treatment, and those who assessed their quality of life noted improvements, indicating that rFVIIa is effective and well-tolerated for managing bleeding in haemophilia patients with inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic treatment of haemophilia patients with inhibitors: clinical experience with recombinant factor VIIa in European Haemophilia Centres. Morfini, M., Auerswald, G., Kobelt, RA., et al.[2016]

Prophylactic treatment is recommended for hemophilic children with inhibitors to prevent musculoskeletal impairment, similar to successful approaches used in children without inhibitors.

Recombinant activated FVII (rFVIIa) is preferred for children due to its recombinant nature, while activated prothrombin complex concentrates (aPCC) can be used in adults or if rFVIIa is ineffective; both have shown effectiveness in controlling bleeding during orthopedic surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of haemophilic arthropathy during childhood. May common orthopaedic management be extrapolated from patients without inhibitors to patients with inhibitors? Rodriguez-Merchan, EC., Hedner, U., Heijnen, L., et al.[2016]

In a study involving 33 male patients with severe hemophilia A, Safacto® demonstrated a significant increase in plasma FVIII activity, reaching an average of 88.84 IU/dl, compared to 100.09 IU/dl for Xyntha®, indicating effective clotting factor replacement.

Both Safacto® and Xyntha® were found to be safe, with no allergic reactions or adverse effects reported, suggesting that Safacto® is a viable alternative to Xyntha® for managing hemophilia A.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative evaluation of the safety and efficacy of recombinant FVIII in severe hemophilia A patients. Abolghasemi, H., Panahi, Y., Ahmadinejad, M., et al.[2022]

A post hoc analysis of patients with severe hemophilia B receiving rFIXFc prophylaxis showed significant reductions in pain, with fewer patients experiencing painful swellings (64% vs. 44%) and painful joints (44% vs. 28%) at the end of the study compared to baseline.

Patients reported improved physical activity, with a notable decrease in those avoiding sports due to hemophilia (47% vs. 27%) and an increase in participation in sports comparable to the general population (52% vs. 37%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

rFIXFc prophylaxis improves pain and levels of physical activity in haemophilia B: Post hoc analysis of B-LONG using haemophilia-specific quality of life questionnaires. Astermark, J., Hermans, C., Ezzalfani, M., et al.[2022]

MonoFIX-VF is a safe and effective treatment for patients with factor IX deficiency (hemophilia B), having replaced Prothrombinex-HT in Australia.

In a study involving four subjects treated for 10 bleeding episodes, including five surgical procedures, MonoFIX-VF demonstrated positive haemostatic effects when administered by continuous infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MonoFIX-VF, a new mono-component factor IX concentrate: a single-centre continuous-infusion study. Evans, G., Collett, M., Came, N., et al.[2019]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2100.1/529157/Motixafortide-for-Hematopoietic-Stem-and

Motixafortide for Hematopoietic Stem and Progenitor Cell ... Compared to plerixafor, motixafortide results in higher and more sustained levels of mobilized PB CD34+ cells with minimal adverse effects ( ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06442761

Study Details | NCT06442761 | SCD Stem Cell ... This study is being done to see if the study drug, motixafortide, is safe in participants with sickle cell disease (SCD). Investigators also want to see if ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S000649712410078X

Motixafortide for Hematopoietic Stem and Progenitor Cell ... Compared to plerixafor, motixafortide results in higher and more sustained levels of mobilized PB CD34+ cells with minimal adverse effects ( ...

4. ir.biolinerx.com ir.biolinerx.com/news-releases/news-release-details/biolinerx-announces-presentations-cost-effectiveness

Release Details - Investors | BioLineRx The analysis demonstrated significant net cost savings with motixafortide plus G-CSF and a greater proportion of patients achieving successful ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10214082/

Innovations in hematopoietic stem-cell mobilization: a review ... Motixafortide plus G-CSF was observed to be safe and well-tolerated when compared with placebo plus G-CSF, with a total 93.8% (75/80) patients experiencing any ...

6. ir.biolinerx.com ir.biolinerx.com/news-releases/news-release-details/biolinerx-announces-oral-presentation-data-phase-1-clinical

Release Details - Investors | BioLineRx "The findings in this trial suggest that patients with sickle cell disease given motixafortide alone, or in combination with natalizumab, could ...

7. stjude.org stjude.org/care-treatment/clinical-trials/scdstemm-sickle-cell-disease.html

SCDSTEMM: Improving Stem Cell Collection in Sickle Cell ... This study aims to see if motixafortide is safe and helps increase collection of stem cells in adults with sickle cell disease. Learn more about the study.