Mavorixafor for WHIM Syndrome

Not currently recruiting at 28 trial locations

Overseen By X4 Pharmaceuticals

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: X4 Pharmaceuticals

Disqualifiers: Pregnancy, Breastfeeding, Hypersensitivity, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of mavorixafor for individuals with WHIM syndrome, a rare condition affecting the immune system by boosting neutrophil levels (a type of white blood cell crucial for fighting infections). The study begins with some participants receiving mavorixafor, while others receive a placebo (a substance with no active drug) for comparison. Following this phase, all participants can receive mavorixafor to assess its safety and tolerability over time. The trial seeks individuals with a confirmed WHIM syndrome mutation, who often experience infections and have low neutrophil counts. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that mavorixafor is likely to be safe for humans?

Research has shown that mavorixafor is generally safe. In one study, it reduced infections by 60% compared to a placebo while maintaining safety. Another study found that 78% of patients tolerated the treatment well. Mavorixafor is easier to manage than treatments like IVIG and filgrastim, as it involves fewer complex procedures. Its safety profile is similar to other approved drugs in its category, such as Mozobil. These findings suggest that mavorixafor is usually well-tolerated by users. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for WHIM syndrome?

Mavorixafor is unique because it targets the underlying cause of WHIM syndrome by inhibiting the CXCR4 receptor, which is involved in the abnormal retention of white blood cells in the bone marrow. Unlike current treatments, such as granulocyte colony-stimulating factor (G-CSF) or antibiotics that mainly address symptoms, Mavorixafor aims to correct the root problem, potentially improving immune function and reducing infections. This targeted mechanism of action is why researchers are particularly excited about Mavorixafor as it offers a more comprehensive approach to managing WHIM syndrome.

What evidence suggests that mavorixafor might be an effective treatment for WHIM syndrome?

Research shows that mavorixafor holds promise for treating WHIM syndrome. In this trial, participants will receive either mavorixafor or a placebo. Studies have found that people taking mavorixafor experienced 60% fewer infections annually compared to those on a placebo. The treatment also increases the number of neutrophils, crucial white blood cells that help fight infections. This suggests that mavorixafor could significantly improve health for people with WHIM syndrome. Overall, the evidence supports mavorixafor's potential effectiveness for this condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Chief Medical Officer

Principal Investigator

X4 Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for individuals with WHIM syndrome, a rare genetic condition. Participants must have a confirmed CXCR4 mutation and low neutrophil counts without infection. They should agree to use effective contraception and comply with the study protocol. It's open to adults and some minors who provide consent.

Inclusion Criteria

I have signed the consent form, or if under 18 (or 16 in certain regions), I and my guardian have both signed.

My white blood cell count is very low without any signs of infection.

You have finished the randomized period of the study or have been released early from it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomized Placebo-Controlled Period

Participants receive either mavorixafor or placebo to assess efficacy by increasing levels of circulating neutrophils

52 weeks

Open-Label Period

Participants receive mavorixafor to evaluate safety and tolerability until commercial availability or study termination

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mavorixafor
• Placebo

Trial Overview The trial is testing Mavorixafor's ability to increase neutrophils in WHIM patients compared to a placebo. Initially, it's double-blind—neither participants nor researchers know who gets what—and then all get Mavorixafor in an Open-Label Period until it’s commercially available or the study ends.

How Is the Trial Designed?

Group I: Mavorixafor Experimental Treatment 1 Intervention

Participants (adults and adolescents \[12 to 17 years of age weighing \>50 kilograms \[kg\]) will receive mavorixafor 400 milligrams (mg) once daily (QD) orally for 52 weeks in the Randomized Placebo-Controlled Period. Adolescents weighing ≤50 kg will receive mavorixafor 200 mg QD. Participants who complete the Randomized Placebo-Controlled Period or are granted Early Release due to recurrent or significant infections, as adjudicated by a blinded, independent adjudication committee (AC), will be offered the opportunity to enroll in the Open-Label Period and receive treatment with mavorixafor 400 mg once daily orally until commercial availability or study termination by the Sponsor.

Group II: Placebo Placebo Group 2 Interventions

Participants will receive placebo matching to mavorixafor QD orally for 52 weeks in the Randomized Placebo-Controlled Period. Participants who complete the Randomized Placebo-Controlled Period or are granted Early Release due to recurrent or significant infections, as adjudicated by a blinded, independent AC, will be offered the opportunity to enroll in the Open-Label Period and receive treatment with mavorixafor 400 mg once daily orally until commercial availability or study termination by the Sponsor.

Who Is Running the Clinical Trial?

X4 Pharmaceuticals

Lead Sponsor

Trials

11

Recruited

400+

Citations

1. ashpublications.org ashpublications.org/blood/article/144/1/1/516732/Mavorixafor-a-new-hope-for-WHIM-syndrome

Mavorixafor: a new hope for WHIM syndrome | Blood Furthermore, the trial reported a 60% reduction in the annualized rate of infection for the mavorixafor group compared with placebo. The safety ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11981379/

Mavorixafor, CXCR4 antagonist, a novel treatment for ... These findings underscore the potential of Mavorixafor to significantly improve clinical outcomes for patients with WHIM syndrome, offering a ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121031049

Mavorixafor, an Oral CXCR4 Antagonist, for Treatment of ... Conclusion: Ongoing long-term treatment of adults with WHIM syndrome with mavorixafor 300 to 400mg shows durable increase in neutrophils and ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03005327

NCT03005327 | A Dose Determination and Safety Study of ... The primary objectives of this Phase 2 study are to determine the safety, tolerability, and dose selection of mavorixafor in participants with WHIM syndrome.

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/218709Orig1s000IntegratedR.pdf

218709Orig1s000 INTEGRATED REVIEW - accessdata.fda.gov study in WHIM syndrome provide substantial evidence of effectiveness of mavorixafor for the indication and establishes the benefit of mavorixafor in ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/218709Orig1s000RiskR.pdf

218709Orig1s000 - accessdata.fda.gov The safety and proposed risk management approach of mavorixafor is similar to Mozobil and Aphexda, the other FDA-approved CXCR4 inhibitors.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1521661623001596

Results of a Phase 3 Trial of an Oral CXCR4 Antagonist ... Mavorixafor, an investigational oral CXCR4 antagonist, demonstrated promising efficacy and safety profiles in a phase 2 trial for participants with WHIM ...