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

Trial Summary

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 the drug Motixafortide a promising treatment for Sickle Cell Disease?

The provided research articles do not contain information about Motixafortide or its effectiveness in treating Sickle Cell Disease, so we cannot determine if it is a promising treatment based on this data. ^{1 2 3 4 5}

What is the purpose of this trial?

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 the drug will help the body increase the number of stem cells that can be collected for possible future transplant use. PRIMARY OBJECTIVE * To characterize the safety and tolerability of motixafortide in participants with SCD as determined by the incidence of adverse events (AEs). SECONDARY OBJECTIVES * To characterize the efficacy of a single dose (Part A) or two doses (Part B) of motixafortide for hematopoietic stem cell (HSC) mobilization and apheresis collection in participants with SCD as determined by the yield of CD34+ cells (CD34+ cells/kg). * To measure the mobilization effects of single-day (Part A) or daily dosing (Part B) dosing with motixafortide in the peripheral blood in participants with SCD as determined by peak peripheral blood CD34+ counts * To recommend a phase 2 dosing strategy based on safety, efficacy, and mobilization effects

Research Team

Akshay Sharma, MBBS, MSc

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

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.

My diabetes is not well-managed.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

References

1. England 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. [2022]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Comparative evaluation of the safety and efficacy of recombinant FVIII in severe hemophilia A patients. [2022]

3. England pubmed.ncbi.nlm.nih.gov

MonoFIX-VF, a new mono-component factor IX concentrate: a single-centre continuous-infusion study. [2019]

4. England 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? [2016]

5. England pubmed.ncbi.nlm.nih.gov

Prophylactic treatment of haemophilia patients with inhibitors: clinical experience with recombinant factor VIIa in European Haemophilia Centres. [2016]