CLINICAL PROTOCOL to Investigate the Long-term Safety and Efficacy of Metreleptin in Various Forms of Partial Lipodystrophy
Condition: Familial Partial Lipodystrophy; Nonalcoholic Steatohepatitis; NAFLD
MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease; Lipodystrophy, Familial Partial; Lipodystrophy
Intervention: Metreleptin
Intervention description: MyaLept (Recombinant-methionyl Human Leptin (r-metHuLeptin) METRELEPTIN) subcutaneous injections
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 5 Years
Healthy volunteers: No

Summary:

      The study investigators' aim is to determine the long term safety and efficacy of Metreleptin
      (Myalept,) in promoting amelioration of metabolic abnormalities in patients with all forms of
      partial lipodystrophy. Patients will be offered this protocol under the following condition:
      Subjects have completed University of Michigan research protocol MB002-014 and have shown
      improved clinical benefit as judged by clinical criteria set forth in this protocol.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Previously completed study protocol:

             o CLINICAL PROTOCOL to investigate the efficacy of recombinant human leptin
             (METRELEPTIN) in nonalcoholic steatohepatitis (NASH) or nonalcoholic fatty liver
             disease (NAFLD) associated with lipodystrophy, MB002-014 (IRMBED: HUM00058708)

          -  Demonstrates clinical benefit as defined by meeting at least one of the following
             criteria upon completion of the above stated protocols:

               -  Reduction of HbA1c ≥ 1.0% or,

               -  Reduction of triglycerides ≥ 30% of baseline or,

               -  Decrease in insulin requirements ≥ 40% or,

               -  Reduction in total NASH score by ≥ 2 points,

               -  Significant worsening of metabolic parameters after discontinuation of
                  Metreleptin if discontinuation has been undertaken.

               -  A health condition that appears to have significantly improved by metreleptin for
                  which two independent health care providers make a request to prevent drug
                  discontinuation. In addition, the PI has to document absence of contraindications
                  for drug continuation (such as bone marrow suppression).

          -  Is male or female ≥ 5 years old at baseline.

          -  Is male, female not of childbearing potential, or meets all the following criteria if
             female of childbearing potential (including perimenopausal women who have had a
             menstrual period within one year):

               -  Not breastfeeding

               -  Negative pregnancy test result (human chorionic gonadotropin, beta subunit) at
                  baseline (not applicable to hysterectomized females).

               -  Must practice and be willing to continue to practice appropriate birth control
                  (defined as a method which results in a low failure rate when use consistently
                  and correctly, such as implants, injectables, oral contraceptives, some
                  intrauterine contraceptive devices, sexual abstinence, tubal ligation, or a
                  vasectomized partner) during the entire duration of metreleptin treatment.

          -  Has physician-confirmed lipodystrophy as defined by evidence of partial (limbs) loss
             of body fat outside the range of normal variation.

          -  If ≥ 18 years of age, is able to read, understand and sign the University of Michigan
             institutional review board (IRBMED) approved informed consent form (ICF), communicate
             with study physician and study team, understand and comply with protocol requirements.

          -  If < 18 and ≥ 7 years of age, is able to read, understand and sign the appropriate
             University of Michigan IRBMED approved assent form and has a parent or legal guardian
             that is able to read, understand and sign the ICF.

          -  If < 7 and ≥ 5 years of age or unable to read, the appropriate assent form must be
             explained to the child.

          -  If previously treated with thiazolidinediones or Vitamin E, stable dose of these
             medications for at least 3 months.

        Exclusion Criteria:

          -  Presence of advanced liver disease (as evidenced by abnormal synthetic function,
             abnormal partial thromboplastin time or albumin).

          -  Evidence of other etiologies of viral hepatitis.

          -  Presence of clinically significant hematologic abnormalities (such as neutropenia
             and/or lymphadenopathy).

          -  Presence of HIV infection.

          -  Inability to give informed consent.

          -  Presence of end stage renal disease, any type of active cancer, or >class 2 congestive
             heart failure ((New York Heart Association Functional Classification System), based on
             medical history and physical examination.

          -  Has known allergies to E. coli-derived proteins or hypersensitivity to any component
             of metreleptin treatment.

          -  Any other condition in the opinion of the investigators that may impede successful
             data collection.