Lipomatosis, Multiple Symmetrical
Conditions
Keywords
Metreleptin
Brief summary
Participants (homozygous MFN2 \[gene that provides instructions to produce the Mitofusin 2 protein\] R707W) will be treated with Metreleptin, and effects on body composition, metabolic parameters and safety will be assessed over a 6 month intervention period. Additional safety will be assessed for 1 more year (up to 1.5 years total) in which adverse event data will be collected.
Detailed description
In 2024, the IRB granted an amendment that allowed for continued data collection, including adverse events, up to 5 years per participant.
Interventions
DRUGMetreleptin
Study drug for injection is supplied in a carton containing 30 vials for reconstitution. Each vial contains 11.3 mg of the study drug as a sterile, white, solid, lyophilized cake or powder to deliver 5 mg/mL of the study drug when reconstituted with 2.2 mL of water for injection (WFI).
Sponsors
Amryt Pharma
University of Michigan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 60 Years
Healthy volunteers
No
Inclusion criteria
* Have the clinical diagnosis of MSL and being followed at University of Michigan (cohort to be studied in this proof-of-concept study is already available at Michigan). * Willing and able to tolerate the study procedures. * Willing and able to tolerate blood sampling. * Having no condition that may impede successful data collection or interfere with testing parameters. * \<60 years of age. * If female of childbearing potential: * Not breastfeeding. * Negative pregnancy test (human chorionic gonadotropin, beta subunit) at baseline. * Can read, understand and sign approved informed consent form, communicate with study physician, and study team, and understand and comply with protocol requirements.
Exclusion criteria
* Presence of advanced liver disease (abnormal synthetic function, prothrombin time \[PT\], or albumin) in medical records * Evidence of other etiologies of viral hepatitis in medical records * Presence of active hematologic, bone marrow or other abnormalities that may increase risk of bleeding in medical records. * Presence of HIV infection in medical records. * Presence of End-stage renal disease (ESRD), active cancer, or \>class 2 congestive heart failure based on medical history and physical examination. * Active chronic infection (e.g., known chronic osteomyelitis or Tuberculosis \[TB\]). May have transient infections but must be free of active infection for two weeks prior to study visits. * Unable to ambulate or tolerate trips to the University of Michigan Clinical Research Unit. * Clinically relevant Coronary artery disease (CAD): history of stent or Coronary artery bypass graft surgery (CABG) with cardiologist confirmed angina. * Presence of autoimmune disease. * Hypersensitivity to metreleptin. * General obesity not associated with congenital leptin deficiency. * Any other condition that, in our opinion, may impede successful data collection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Truncal Adiposity | Baseline, Week 24 | A dual-energy X-ray absorptiometry (DEXA) scan was used to measure truncal adiposity at baseline and week 24. Truncal adiposity is the amount of fat a person has in the trunk area, and this outcome measure looked at the change in the fat in this area of the body in relation to the total fat in the participant's body. Results represent the change in the percentage of fat tissue from the trunk area to the total body. |
| Change in Total Adiposity | Baseline, Week 24 | A dual-energy X-ray absorptiometry (DEXA) scan was used to measure total adiposity at baseline and week 24. Total adiposity is the amount of fat participants had in the body compared to their total weight. Results represent the change in the percentage of fat tissue from the total body to the total weight. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients With MSL Metreleptin: Study drug for injection is supplied in a carton containing 30 vials for reconstitution. Each vial contains 11.3 mg of the study drug as a sterile, white, solid, lyophilized cake or powder to deliver 5 mg/mL of the study drug when reconstituted with 2.2 mL of water for injection (WFI). | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Patients With MSL |
|---|---|
| Age, Continuous | 38.5 years STANDARD_DEVIATION 19.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 4 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Change in Total Adiposity
A dual-energy X-ray absorptiometry (DEXA) scan was used to measure total adiposity at baseline and week 24. Total adiposity is the amount of fat participants had in the body compared to their total weight. Results represent the change in the percentage of fat tissue from the total body to the total weight.
Time frame: Baseline, Week 24
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Patients With MSL | Change in Total Adiposity | Baseline | 21.9 percentage of body weight | Standard Deviation 2.3 |
| Patients With MSL | Change in Total Adiposity | Week 24 | 16.7 percentage of body weight | Standard Deviation 4.7 |
p-value: <0.0001t-test, 2 sided
Primary
Change in Truncal Adiposity
A dual-energy X-ray absorptiometry (DEXA) scan was used to measure truncal adiposity at baseline and week 24. Truncal adiposity is the amount of fat a person has in the trunk area, and this outcome measure looked at the change in the fat in this area of the body in relation to the total fat in the participant's body. Results represent the change in the percentage of fat tissue from the trunk area to the total body.
Time frame: Baseline, Week 24
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Patients With MSL | Change in Truncal Adiposity | Baseline | 22.8 percentage of truncal body fat | Standard Deviation 3.2 |
| Patients With MSL | Change in Truncal Adiposity | Week 24 | 16.0 percentage of truncal body fat | Standard Deviation 6 |
p-value: 0.004t-test, 2 sided