A treatment study in patients with WHIM Syndrome.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

X4 Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

12 Jan 2026 → 12 Jan 2026

Decision date (initial)

2024-11-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

X4 Pharmaceuticals Incorporated

External identifiers

EU CT number

2024-518461-10-00

EudraCT number

2019-001153-10

ClinicalTrials.gov

NCT03995108

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety, Pharmacodynamic, Pharmacokinetic

-Randomized Placebo-Controlled Period: To demonstrate the efficacy of mavorixafor in participants with Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) syndrome as assessed by increasing levels of circulating neutrophils compared with placebo and relative to a clinically meaningful threshold.
-Open label period: To evaluate the long-term safety and tolerability of mavorixafor in participants with WHIM syndrome

Secondary objectives 2

1. Secondary Objective for Randomized Period: 1. To demonstrate the efficacy of mavorixafor in participants with WHIM syndrome as assessed by increasing levels of circulating lymphocytes compared with placebo and relative to a clinically meaningful threshold. 2. To demonstrate the clinical efficacy of mavorixafor in participants with WHIM syndrome as assessed by a composite endpoint of infections and warts. 3. To demonstrate the efficacy of mavorixafor in participants with WHIM syndrome as assessed by improvement in warts. 4. To demonstrate the efficacy of mavorixafor in participants with WHIM syndrome as assessed by reduction in infections.
2. Secondary Objective for Open-Label Period: To evaluate the long-term efficacy of mavorixafor in participants with WHIM syndrome.

Conditions and MedDRA coding

WHIM Syndrome

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002490-PIP01-18

Plan to share IPD

Yes

IPD plan description

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, X4 Pharmaceuticals, Inc. will continue to protect the privacy of our clinical trial participants.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Inclusion criteria for Randomized Period: 1. Be at least 12 years of age. 2. Have signed the current approved Informed Consent Form. Participants under 18 years of age (in the Netherlands and other applicable regions, participants under 16 years of age) will sign an approved informed assent form and must also have a signed parental/legal guardian consent. 3. Have a genotype-confirmed mutation of CXCR4 consistent with WHIM phenotype. 4. Agree to use a highly effective form of contraception, as detailed in Section 5.3.1. 5. Be willing and able to comply with this protocol. 6. Have a confirmed ANC ≤ 400 cells/μL during screening, obtained while participant has no clinical evidence of infection.
2. Inclusion criteria for Open-Label Period: 1. Completed the Randomized Placebo-Controlled Period. 2. Granted Early Release from the Randomized Placebo-Controlled Period. 3. Blind broken.

Exclusion criteria 1

1. Exclusion criteria for Randomized Period: 1. Has known systemic hypersensitivity to the mavorixafor drug substance, its inactive ingredients, or the placebo. 2. Is pregnant or breastfeeding. 3. Has a known history of a positive serology or viral load for HIV or a known history of AIDS. 4. Has, at screening, laboratory tests meeting 1 or more of the following criteria: − A positive hepatitis C virus antibody with confirmation by hepatitis C virus ribonucleic acid polymerase chain reaction reflex testing. − A positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). − NOTE: If a participant tests negative for HBsAg, but positive for HBcAb, the participant would be considered eligible if the participant tests positive for hepatitis B surface antibody (also referred to as anti-HBsAg) on reflex testing. 5. Has, at screening, safety laboratory tests meeting 1 or more of the following criteria: − Hemoglobin < 8.0 g/dL − Platelets < 75,000 cells/μL − Estimated glomerular filtration rate based on the Modification of Diet in Renal Disease of ≤ 29 mL/min/1.73 m2 (Stage 4 or 5 chronic kidney disease) − Serum aspartate aminotransferase > 2.5 × ULN − Serum alanine aminotransferase > 2.5 × ULN − Total bilirubin > 1.5 × ULN (unless due to Gilbert’s syndrome, in which case total bilirubin ≥ 3.0 × ULN and direct bilirubin > 1.5 × ULN) 6. Had surgery requiring general anesthesia within the 4 weeks prior to Day 1. 7. Received any of the following treatments: − Plerixafor within 6 months prior to Day 1. − Chronic or prophylactic use of antibiotics (systemic or inhaled) within 4 weeks prior to Day 1. − Chronic or prophylactic use of G-CSF or granulocyte macrophage-colony stimulating factor within 2 weeks of Day 1. − Chronic or prophylactic use of systemic glucocorticoid use (> 5 mg prednisone equivalent per day) within 2 weeks prior to Day 1. − Any investigational therapy within 5 half-lives or 2 weeks prior to Day 1, whichever is longer. Prior use of any investigational therapies must be discussed with the Medical Monitor. 8. Is currently taking or has, within 2 weeks prior to Day 1, received any medication that is prohibited (see Section 6.4.1), based on potential for drug-drug interactions. 9. Has, at the planned initiation of study drug, a clinically diagnosed active infection (excluding warts) that has the potential to raise the ANC counts. 10. Has had a total splenectomy within 1 year. 11. Has a current diagnosis of myelofibrosis. 12. Has a medical history of hematological malignancies. 13. Has any other medical or personal condition that, in the opinion of the Investigator, may potentially compromise the safety or compliance of the participant or may preclude the participant’s successful completion of the clinical study. 14. Has corrected QT interval using Fridericia’s formula of > 450 ms.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Randomized Placebo-Controlled Period: Time above threshold-absolute neutrophil count (TAT-ANC; in hours) of ≥ 500 cells/μL over a 24-hour period, assessed 4 times throughout the study (every 3 months for 12 months) for the Intent-to-Treat (ITT) Population.
2. Open-Label Period: Safety and tolerability of mavorixafor in participants with WHIM syndrome, as assessed by adverse events (AEs), clinical laboratory evaluations, vital signs, electrocardiogram (ECG) assessments, physical and ophthalmologic examinations.

Secondary endpoints 7

1. Randomized Placebo-Controlled Period: 1. Time above threshold-absolute lymphocyte count (TAT-ALC) of ≥ 1000 cells/μL over a 24-hour period assessed 4 times throughout the study (every 3 months for 12 months) in the ITT Population. 2. Composite Clinical Efficacy Endpoint for mavorixafor based on total infection score and total wart change score in the ITT Population.
2. 3. Total wart change score for mavorixafor based on central blinded, independent review of 3 target skin regions in the ITT Population. 4. Total infection score for mavorixafor based on number and severity of infections adjudicated by a blinded, independent Adjudication Committee (AC) in the ITT Population.
3. Open-Label Period: 1. Proportion of neutrophil responders, defined as participants with ANC ≥ 500 cells/μL threshold. 2. Proportion of lymphocyte responders, defined as participants with baseline ALC below the lower limit of normal who achieve on-treatment ALC ≥ 1000 cells/μL threshold.
4. 3. Absolute and fold change from baseline for total ALC, AMC, ANC, and WBC count. 4. Vaccine titer levels during the Open-Label Period in all participants vaccinated with Tdap) during the study, including pertussis toxin and tetanus.
5. 5. Vaccine titer levels during the Open-Label Period for HPV 16 and HPV 18 in all participants receiving vaccinations with HPV 9-valent vaccine, recombinant (Gardasil®9) during the study. 6. Change from baseline in cutaneous warts, based on central review of CGI-C and CGI-S.
6. 7. Change from baseline in cutaneous warts, based on local dermatologist review of CGI-C and CGI-S. 8. Change over time in PGI-S and PGI-C. 9. Total infection score as adjudicated by an independent AC.
7. For the full list of endpoints please refer to the protocol.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

X4 Pharmaceuticals Inc.

Sponsor organisation

X4 Pharmaceuticals Inc.

Address

61 North Beacon Street

City

Boston

Postcode

02134-1912

Country

United States

Scientific contact point

Organisation

X4 Pharmaceuticals Inc.

Contact name

Kathleen Galvez

Public contact point

Organisation

X4 Pharmaceuticals Inc.

Contact name

Candida Fratazzi

Third parties 7

Locations

5 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 34 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications