Open-label Extension Study to Evaluate Metreleptin in Patients With Partial Lipodystrophy

An Open-label Extension of APG-20 Study to Evaluate the Long-term Safety and Efficacy of Daily Subcutaneous Metreleptin Treatment in Subjects With Partial Lipodystrophy

This Phase 3 study is an Open Label Extension of the APG-20 Study To Evaluate the Long-term Safety and Efficacy of Daily Subcutaneous Metreleptin Treatment in Subjects with Partial Lipodystrophy

Study Overview

• Status: Recruiting
• Conditions: Familial Partial Lipodystrophy
• Intervention / Treatment: Drug: Metreleptin

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Lori Hartnett, PhD; Phone Number: +3905212791; Email: clinicaltrials_info@chiesi.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama
      • Contact: Fernando Ovalle
      • Principal Investigator: Fernando Ovalle
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Recruiting
      • Flourish Research
      • Principal Investigator: Rasha Youssef
      • Contact: Rasha Youssef
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Lindsay Fourman, MD
      • Principal Investigator: Lindsay Fourman, MD
  • Michigan
    • Ann Arbour, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Principal Investigator: Elif Oral, MD
      • Contact: Elif Oral, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Not yet recruiting
      • Children's Hospital of Philadelphia
      • Principal Investigator: Vaneeta Bamba, MD
      • Contact: Vaneeta Bamba, MD
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT Southwestern Medical Center
      • Principal Investigator: Abhimanyu Garg, MD
      • Contact: Abhimanyu Garg, MD
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • The Medical College of Wisconsin
      • Contact: Bradley Javorsky, MD
      • Principal Investigator: Bradley Javorsky, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥13 years of age, inclusive, at the time of signing the informed consent form (ICF).
2. Subjects must have completed the Parent study APG-20 and, in the opinion of the Investigator and Sponsor, have been compliant with study procedures through Parent study Month 12 visit.
3. Negative pregnancy test (urine or serum) for female subjects of childbearing potential
4. Female subjects must be postmenopausal (defined as cessation of menses for at least 1 year), surgically sterile (hysterectomy, bilateral oophorectomy, or tubal ligation), or willing to use a highly effective method of contraception (such methods include combined [estrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation: oral/intravaginal; transdermal/progestogen-only hormonal contraception associated with inhibition of ovulation: oral/injectable; implantable/intrauterine device [IUD]/intrauterine hormone-releasing system [IUS]/bilateral tubal occlusion/vasectomized partner/sexual abstinence) for the duration of the study (from the time they sign an ICF, until 4 weeks after the last dose of study treatment). Hormonal contraception alone (including oral, injectable, transdermal, and implantable) is not acceptable; an additional barrier method must be used. Intravaginal hormonal contraception or IUS alone are allowed per Investigator's discretion. Subjects on oral contraceptives will not be required to discontinue medication. Subjects will not be permitted to commence oral contraceptives while taking study treatment during the study.
5. Male subjects must be surgically sterile or willing to use an acceptable method of contraception for the duration of the study (from the time they sign an ICF), until 4 weeks after the last dose of study treatment. An acceptable method of contraception would be a barrier method, such as condoms, restraining from having sex, or a partner using the approved methods of contraception for female subjects as per Inclusion Criteria #4.
6. Subjects who are blood/egg/sperm donors should be willing to halt donations during the study and for 4 weeks following their last dose of study treatment.
7. Subjects who are willing to provide informed consent/assent prior to any study-specific procedures. If a minor, the subject has a parent or legal guardian able to read, understand, and sign the ICF and/or a Child Assent Form (if applicable), communicate with the Investigator, and understand and comply with the protocol requirements. Adolescent subjects must also read and understand the Child Assent Form.
8. Subjects who are willing to follow the dietary restrictions recommended by the Investigator.

Exclusion Criteria:

1. Severe hypersensitivity reactions to the study treatment of the Parent study APG-20.
2. Known to have tested positive for human immunodeficiency virus (HIV) or known to be diagnosed with HIV-related LD. Positive HIV test in countries requiring HIV testing.
3. Are immunocompromised or receiving immunomodulatory drugs.
4. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for subjects ≥18 years of age and by Bedside Schwartz for subjects <18 years of age.
5. Diagnosis of clinically significant hematological abnormalities (including but not limited to clinically significant leukopenia, neutropenia, bone marrow abnormalities, leukemia or lymphoma, or clinically significant pathological lymphadenopathy).
6. Malignancy that is ongoing/not in remission or that currently requires or has required active treatment within the past year (with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ [e.g., breast carcinoma, cervical cancer in situ] that have undergone potentially curative therapy).
7. For females only: currently pregnant (confirmed with a positive pregnancy test) or breastfeeding.
8. Any condition where, in the opinion of the Investigator, participation in this study may pose a significant risk to the subject.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metreleptin; Metreleptin [Recombinant-methionyl human Leptin; r-metHuLeptin] for daily injection is a sterile, white, solid lyophilised cake	Drug: Metreleptin; Metreleptin is a recombinant human leptin analog that is indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the Incidence and Frequency of Treatment-Emergent Adverse Events (Safety and Tolerability)	Incidence and frequency of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), treatment-related TEAEs, adverse events of special interest (AESI), and adverse events leading to study treatment discontinuation/withdrawal from the study	From enrollment to the end of treatment (until the last participant completes 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the long-term efficacy (HbA1c) of daily SC metreleptin treatment in participants with familial partial lipodystrophy (FPLD)	Glycated hemoglobin (HbA1c) in participants with HbA1c ≥7% at the Parent study Baseline, over time during the OLE	From enrollment to the end of treatment (until the last participant completes 24 months)
To evaluate the long-term efficacy (TGs) of daily SC metreleptin treatment in participants with FPLD	- Fasting triglycerides (TGs) in participants with TG ≥500 mg/dL at the Parent study Baseline, over time during the OLE	From enrollment to the end of treatment (until the last participant completes 24 months)
To evaluate the long-term efficacy (FBG) of daily SC metreleptin treatment in participants with FPLD	Fasting blood glucose (FBG) in participants with HbA1c ≥7% at the Parent study Baseline, over time during the OLE; FBG in participants with FBG above upper limit of normal (ULN) at the Parent study Baseline, over time during the OLE	From enrollment to the end of treatment (until the last participant completes 24 months)

Collaborators and Investigators

• Sponsor: Amryt Pharma

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 5, 2024
• First Submitted That Met QC Criteria: November 6, 2024
• First Posted (Actual): November 7, 2024

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 30, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Metreleptin; familial partial lipodystrophy
• Additional Relevant MeSH Terms: Laminopathies; Genetic Diseases, Inborn; Metabolic Diseases; Skin Diseases; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Skin Diseases, Metabolic; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Lipodystrophy; Lipodystrophy, Familial Partial; metreleptin
• Other Study ID Numbers: APG-20-OLE; APG-20 OLE (Other Identifier: Amryt Pharmaceuticals DAC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No