Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy

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Brief Title

Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy

Official Title

Compassionate Use of Metreleptin in Previously-Treated Patients With Generalized Lipodystrophy

Brief Summary


      - Generalized lipodystrophy can cause high blood fat levels and resistance to insulin. This
      can lead to health problems including diabetes. Researchers have found that the drug
      metreleptin improves health in people with this disease.


      - To test the safety and effectiveness of metreleptin.


        -  People ages 6 months and older with generalized lipodystrophy who:

        -  have received metreleptin through NIH studies AND

        -  cannot get it through approved or compassionate use mechanisms in their home country.


        -  Participants will come to NIH approximately every 6 months during year one, then every 1
           2 years. Financial assistance may be available for travel within the U.S.

        -  At visits, participants will get a supply of metreleptin to take home for daily
           injections. They will have:

        -  plastic catheter placed in an arm vein.

        -  blood tests, urine collection, and physical exam.

        -  oral glucose tolerance test, drinking a sweet liquid.

        -  ultrasound of the heart, liver, uterus, and ovaries. A gel and a probe are placed on the
           skin and pictures are taken of the organs.

        -  echocardiogram, which takes pictures of the heart with sound waves.

        -  Resting Metabolic Rate taken. A plastic hood is worn over the head while the oxygen they
           breathe is measured.

        -  Participants will have up to 3 DEXA scan x-rays per year.

        -  Participants may have:

        -  annual bone x-rays.

        -  liver biopsies every few years. A needle will be inserted into the liver to obtain a
           small piece. Participants will sign a separate consent for this.

        -  Participants must be seen regularly by their local doctors and have blood tests at least
           every 3 6 months at home.

Detailed Description

      Leptin is an adipocyte-derived hormone that can be thought of as a signal from adipose tissue
      to the rest of the body conveying information about long-term nutritional status. Patients
      with the very rare condition of generalized lipodystrophy have leptin deficiency secondary to
      lack of adipose tissue. The combination of leptin deficiency and ectopic lipid deposition in
      patients with lipodystrophy leads to metabolic complications including severe insulin
      resistance and diabetes, hypertriglyceridemia, nonalcoholic steatohepatitis, and polycystic
      ovarian syndrome. Between 2000 and 2014, the NIDDK IRP conducted an open-label clinical trial
      of the recombinant human leptin analog, metreleptin, in patients with generalized and partial
      forms of lipodystrophy. This study showed that metreleptin ameliorates metabolic and
      endocrine abnormalities in lipodystrophy, including reducing food intake, improving insulin
      resistance and diabetes, reducing ectopic lipid, and normalizing reproduction. Based on these
      data, metreleptin was approved by the FDA in February, 2014, for patients with generalized,
      but not partial, lipodystrophy.

      Currently, metreleptin is not available as an approved drug outside the US and Japan, and it
      is available on a compassionate use basis only in a few additional countries. The purpose of
      this study is twofold:

        1. To provide access to metreleptin to patients with generalized lipodystrophy, including
           those who have previously received metreleptin through NIH studies (protocols 02-DK-0022
           and 13-DK- 0057) AND/OR who cannot obtain metreleptin through approved or compassionate
           use mechanisms in their home country

        2. To continue to collect data on the long-term efficacy of metreleptin in ameliorating the
           metabolic complications of generalized lipodystrophy.

      Metreleptin will be given at doses of less than or equal to 0.24 mg/kg/day, adjusted based on
      body weight and metabolic control. Patients will be seen approximately once per year at NIH
      for evaluation, and potentially less frequently for those who are medically stable and have
      difficulty traveling to the US. Laboratory evaluation will be obtained more frequently by the
      patient s home providers as clinically indicated. The primary outcomes of the study are
      improvements in serum triglycerides and hemoglobin A1c levels. Secondary outcomes include
      measures of steatohepatitis and ectopic lipid, body composition, bone mineral density and
      bone mineral metabolism, and pituitary and reproductive function.

      Metreleptin is supplied by Amryt Pharma. Neither the NIH nor Amryt Pharma can guarantee that
      leptin will be available for these patients indefinitely and/or after the study ends.

Study Phase

Phase 3

Study Type


Primary Outcome

Serum triglycerides

Secondary Outcome






Study Arms / Comparison Groups

 Leptin study drug
Description:  Administration of study drug SQ BID


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

October 9, 2014

Completion Date

July 31, 2025

Primary Completion Date

July 31, 2025

Eligibility Criteria


               1. Age greater than or equal to 6 months.

               2. Generalized lipodystrophy (either congenital or acquired).

               3. Those who cannot obtain metreleptin through approved or compassionate use
                  mechanisms in their home country.


          1. Availability of metreleptin to the patient either as an approved drug, or through
             local compassionate use or expanded access programs.

          2. Known HIV infection or HIV-associated lipodystrophy.

          3. Any medical condition or medication that will increase risk to the subject.

          4. Current alcohol or substance abuse.

          5. Subjects who have a known hypersensitivity to E. coli derived proteins (as leptin is
             derived from such proteins).




6 Months - N/A

Accepts Healthy Volunteers



Rebecca J Brown, M.D., (301) 402-6371, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study Sponsor

Rebecca J Brown, M.D., Principal Investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Verification Date

February 25, 2022