Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy

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

Background:

- 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.

Objective:

- To test the safety and effectiveness of metreleptin.

Eligibility:

• 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.

Design:

• 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetes; Hyperlipidemia; Lipodystrophy
• Intervention / Treatment: Drug: Metreleptin

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 Chiesi USA, Inc.. Neither the NIH nor Chiesi USA, Inc. can guarantee that leptin will be available for these patients indefinitely and/or after the study ends.

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

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• INCLUSION 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.

EXCLUSION CRITERIA:

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).

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
Other: Leptin study drug; Administration of study drug SQ BID	Drug: Metreleptin; administered subcutaneously 1-2 times/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum triglycerides	Improvements in lab value.	every 6-12 months
Serum hemoglobin A1C	Improvements in lab value.	every 6-12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Steatohepatosis	stable or improvements	every 12 months
Pituitary & Reproductive Function	stable or improvements	every 6-12 months
Ectopic lipid & body composition	stable or improvements	every 12 months
Bone mineral density & metabolism	stable or improvements	every 12 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Brown RJ, Meehan CA, Cochran E, Rother KI, Kleiner DE, Walter M, Gorden P. Effects of Metreleptin in Pediatric Patients With Lipodystrophy. J Clin Endocrinol Metab. 2017 May 1;102(5):1511-1519. doi: 10.1210/jc.2016-3628.
• Malandrino N, Reynolds JC, Brychta RJ, Chen KY, Auh S, Gharib AM, Startzell M, Cochran EK, Brown RJ. Visceral fat does not contribute to metabolic disease in lipodystrophy. Obes Sci Pract. 2019 Jan 24;5(1):75-82. doi: 10.1002/osp4.319. eCollection 2019 Feb.
• Meral R, Ryan BJ, Malandrino N, Jalal A, Neidert AH, Muniyappa R, Akinci B, Horowitz JF, Brown RJ, Oral EA. "Fat Shadows" From DXA for the Qualitative Assessment of Lipodystrophy: When a Picture Is Worth a Thousand Numbers. Diabetes Care. 2018 Oct;41(10):2255-2258. doi: 10.2337/dc18-0978.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2014
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: October 10, 2014
• First Submitted That Met QC Criteria: October 10, 2014
• First Posted (Estimated): October 13, 2014

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 9, 2026
• Last Verified: May 8, 2026

More Information

Terms related to this study

• Keywords: Diabetes; Leptin; Lipodystrophy; Hypertriglyceridemia
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Skin Diseases; Dyslipidemias; Lipid Metabolism Disorders; Skin Diseases, Metabolic; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Diabetes Mellitus; Hypertriglyceridemia; Lipodystrophy; Hyperlipidemias; metreleptin
• Other Study ID Numbers: 150003; 15-DK-0003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Subject level data will be shared upon request after appropriate collaboration agreements are in place.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No