Testing HM15421 (GC1134A) for safety and tolerability in people with Fabry disease

An Open Label, Dose Range, Proof-of-Concept Study to Assess the Safety and Efficacy of HM15421/GC1134A in Patients With Fabry Disease

This Phase 1/2 study will test whether HM15421 (GC1134A) is safe and well tolerated in adults with Fabry disease and will collect early data on how the drug behaves in the body and affects disease markers.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: GC Biopharma Corp (Industry-sponsored)
• Locations: 10 sites (Los Angeles, California and 9 other locations)
• Trial ID: NCT06858397 on ClinicalTrials.gov

What this trial studies

This is a first-in-human Phase 1/2 study designed to test safety, tolerability, pharmacokinetics (PK), and early signs of efficacy of HM15421 in adults with Fabry disease. Eligible participants have genetically or enzymatically confirmed Fabry disease, are treatment-naive for the prior 6 months, have eGFR ≥ 60 mL/min/1.73 m2, and elevated plasma lyso-Gb3. The study will enroll participants at several U.S. academic medical centers and is sponsored by GC Biopharma with collaborator Hanmi Pharmaceutical. Participants will be treated in dose cohorts with PK sampling, safety monitoring, and biomarker measurements to look for initial signals of activity.

Who should consider this trial

Good fit: Adults (≥18) with documented Fabry disease—either pathogenic GLA variant in females or low alpha-galactosidase activity in males—who are treatment-naive for 6 months, have eGFR ≥ 60, plasma lyso-Gb3 >1.5×ULN, and negative ADA at screening are ideal candidates.

Not a fit: Patients with advanced kidney impairment (eGFR <60), recent or ongoing FD therapy, positive anti-drug antibodies, children, or those without confirmed pathogenic GLA variants are unlikely to qualify or receive benefit from this early-phase trial.

Why it matters

Potential benefit: If successful, HM15421 could become a new treatment option that is safe and helps reduce disease-related biomarkers and symptoms in people with Fabry disease.

How similar studies have performed: Approved enzyme replacement therapies and oral chaperones have improved outcomes for some people with Fabry disease, but HM15421 is a first-in-human agent representing a novel therapeutic approach.

Eligibility criteria

Inclusion Criteria:

1. Participants must be ≥ 18 years of age or age considered as adult in the respective country at the time of signing the informed consent.
2. Documented diagnosis of FD with clinical symptoms.
3. Females: historical genetic test results based on identification of pathogenic or likely pathogenic GLA variant of FD.
4. Males: Plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than lower limit of normal (LLN in plasma=3.2 nmol/hr/mL, LLN in leucocytes=32 nmol/hr/mg/protein).
5. Patients who are naive or have not received FD therapy including investigational therapy for FD within the past 6 months prior to screening and have negative ADA testing at screening.
6. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
7. Plasma lyso-Gb3 levels greater than 1.5 times the upper limit of normal (ULN).
8. Male participants:

   * Male participants are eligible to participate if they agree to the following during the study treatment period:
   * Refrain from donating sperm,

   PLUS either:
   * Be abstinent from heterosexual intercourse with a woman of childbearing potential (WOCBP) as their preferred and usual lifestyle (abstinent on a longterm and persistent basis) and agree to remain abstinent, OR
   * Must agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person,
   * In addition to male condom, use of highly effective method of contraception may be considered in WOCBP partners of male participants.
9. Female participants:

   * Female participants are eligible to participate if they are not pregnant or breastfeeding, and at least 1 of the following conditions applies:

     * Is not a WOCBP, OR
     * Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \< 1% per year), preferably with low user dependency, starting at least one menstrual cycle before first study drug administration and continuing for at least 30 days after the end of systemic exposure of the study drug and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The Investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study drug.
     * A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study drug.
     * If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
   * Women whose postmenopausal status is recent, may perform additional follicle stimulating hormone (FSH) testing.

   Informed Consent
10. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

1. Women who are pregnant, planning to become pregnant during the study, or are breast feeding.
2. History of dialysis or renal transplantation.
3. CKD stage ≥ 3.
4. History of acute kidney injury within 12 months prior to screening, including specific kidney diseases (eg, acute interstitial nephritis, acute glomerular and vasculitic renal diseases); non-specific conditions (eg, ischemia, toxic injury); as well as extrarenal pathology (eg, prerenal azotemia, and acute postrenal obstructive nephropathy).
5. Urine protein to creatinine ratio (UPCR) \> 0.5 g/g and not treated with an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB).
6. Known history of hypersensitivity to any ingredient in the investigational product and to Gadolinium contrast agent that is not managed by the use of premedication.
7. Cardiovascular event (myocardial infarction, unstable angina) within 6 months before screening.
8. Congestive heart failure New York Heart Association (NYHA) Class IV
9. History of stroke.
10. Pacemaker or other contraindication for magnetic resonance imaging (MRI) scanning.
11. Angiotensin converting enzyme inhibitor or ARB therapy initiated or dose changed in the 4 weeks prior to screening.
12. Patients who received investigational gene therapy for FD.
13. Participation in other studies involving study drugs within 4 weeks prior to study entry and/or during study participation.
14. Participating in interventional study or using compassionate access product for FD. Participants who have participated in interventional trials for conditions not related to FD should be enrolled after the adequate wash out period is over, which is 5 half-lives or 30 days whichever is longer.
15. Presence of human immunodeficiency virus (HIV) and/or active (acute or chronic) hepatitis B and/or Hepatitis C infections.
16. Presence of any medical, emotional, behavioral, or psychological condition that, in the judgment of the Investigator and/or Medical Monitor, would interfere with the participant's compliance with the requirements of the study.
17. Participants who may have history of deliberate self-harm or suicidal ideation.

Where this trial is running

Los Angeles, California and 9 other locations

• David Geffen School of Medicine UCLA, UCLA Health — Los Angeles, California, United States (Recruiting)
• University of Kansas School of Medicine — Kansas City, Kansas, United States (Recruiting)
• University of Minnesota — Minneapolis, Minnesota, United States (Recruiting)
• Children's Hospital Medical Center — Cincinnati, Ohio, United States (Recruiting)
• University of Pittsburgh Medical Center Children's Hoispital of Pittsburgh — Pittsburgh, Pennsylvania, United States (Recruiting)
• Lysosomal and Rare Disorders Research and Treatment Center — Fairfax, Virginia, United States (Recruiting)
• Centro Medico IPAM — Rosario, Santa Fe Province, Argentina (Recruiting)
• Hospital Italiano de Buenos Aires — Buenos Aires, Argentina (Recruiting)
• Pusan National University Children's Hospital in Yangsan — Yangsan, Gyeongsangnam-do, South Korea (Recruiting)
• Yonsei University, College of Medicine — Seoul, South Korea (Recruiting)

Study contacts

• Study coordinator: GC Biopharma

Conditions Fabry Disesase