Familial Partial LipodystrophyPhase 2LEAPNCT05088460
A Study to Examine the Effects of the Leptin Receptor (LEPR) Agonist Antibody REGN4461 in Adult Patients With Familial Partial Lipodystrophy (FPLD)
A Phase 2 study testing REGN4461 in people with Familial Partial Lipodystrophy and Metabolic Abnormalities, run by Regeneron Pharmaceuticals at 8 sites in 4 countries.
Trial summary
Two cohorts are being studied based on leptin levels. Cohort A is composed of patients with baseline leptin <8.0 ng/mL and Cohort B is composed of patients with baseline leptin 8.0 to ≤20.0 ng/mL The primary objectives will be evaluated for patients in Cohort A only: To evaluate the effect of REGN4461 on fasting… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Familial Partial Lipodystrophy, Metabolic Abnormalities
- What is being tested?
- REGN4461
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 8 sitesin 4 countries
- Study dates
- 28 Feb 2022to 18 Apr 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical diagnosis of familial partial lipodystrophy as defined in the protocol
- Fasting leptin level ≤20.0 ng/ml, as determined during the screening period
- Presence of significant metabolic abnormalities related to glucose and triglycerides (TGs) as defined in the protocol
- Stable body weight within the 3 months prior to screening (no gain or loss of >5% current weight)
- Stable diet during the past 3 months defined as no major change in macronutrient composition (eg, starting or stopping diets such as Atkins, Paleo, Vegetarianism, Veganism)
- No clinically meaningful change in medication regimen in the 3 months prior to screening as defined in the protocol
Who cannot join
- Treatment with metreleptin within 3 months of the screening visit
- Patients with a diagnosis of generalized lipodystrophy
- Patients with a diagnosis of acquired lipodystrophy
- Pregnant or breastfeeding women
- NOTE: Other protocol defined inclusion/exclusion criteria apply
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
United States5 sites
University of Michigan
Ann Arbor, Michigan, 48109
National Institute of Health
Bethesda, Maryland, 20892
Excel Medical Clinical Trials - A Flourish Research Site
Boca Raton, Florida, 33434
UT Southwestern Medical Center
Dallas, Texas, 75390
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Spain1 site
Complexo Hospitalario Universitario de Santiago-Hospital Médico-Cirúrxico de Conxo
Santiago de Compostela, Galicia, 15706
Turkey (Türkiye)1 site
Ege University Faculty of Medicine
Izmir, Bornova, 35100
About this study
Official title: A Randomized Double-Blind Placebo-Controlled Study of the LEPR Agonist Antibody REGN4461 for the Treatment of Metabolic Abnormalities in Patients With Familial Partial Lipodystrophy
Two cohorts are being studied based on leptin levels. Cohort A is composed of patients with baseline leptin <8.0 ng/mL and Cohort B is composed of patients with baseline leptin 8.0 to ≤20.0 ng/mL
The primary objectives will be evaluated for patients in Cohort A only:
Read more
- To evaluate the effect of REGN4461 on fasting triglycerides (TG) in patients with elevated baseline fasting TG
- To evaluate the effect of REGN4461 on hyperglycemia in patients with elevated baseline Hemoglobin A1c (HbA1c)
The following secondary objectives of the study will be evaluated for Cohort B and for the combined set of Cohorts A plus B:
- To evaluate the effect of REGN4461 on fasting TG levels in patients with hypertriglyceridemia
- To evaluate the effect of REGN4461 on glycemic control in patients with hyperglycemia
The following secondary objectives of the study will be evaluated for Cohorts A and B separately, and for the combined set of Cohorts A plus B:
- To evaluate the effect of REGN4461 on liver fat in patients with hepatic steatosis
- To evaluate the effect of REGN4461 on hunger
- To evaluate safety and tolerability of REGN4461
- To characterize the concentration profile of REGN4461 over time
- To assess immunogenicity to REGN4461
- Being tested
- REGN4461, Matching Placebo
- Medical subject headings
- Lipodystrophy, Familial Partial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
REGN4461Drug
Also called mibavademab
Intravenous (IV) infusion loading dose followed by subcutaneous (SC) injection weekly (QW).
Matching PlaceboDrug
Intravenous (IV) infusion loading dose followed by subcutaneous (SC) injection weekly (QW).
| Study group | Role | What they receive |
|---|---|---|
| Study Arm 1 | Experimental | Randomized to placebo for 12 weeks and then crossover to REGN4461 for 12 weeks Receives: Drug: REGN4461; Drug: Matching Placebo |
| Study Arm 2 | Experimental | Randomized to receive REGN4461 for 24 weeks Receives: Drug: REGN4461 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline to Week 12 in Fasting Serum Triglyceride (TG) (Cohort A)
Percentage change in fasting serum TG was reported for participants with elevated baseline fasting TG (> 200 mg/dL) and with baseline leptin < 8.0 ng/mL (Cohort A).
Measured: Baseline to week 12
Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) (Cohort A)
Change in HbA1c was reported for participants with elevated baseline HbA1c (> 7.0%) and with baseline leptin < 8.0 ng/mL (Cohort A).
Measured: Baseline to week 12
Secondary outcomes (17)
Percent Change From Baseline to Week 12 in Fasting Serum TG (Cohorts B and A + B)
Percent change in fasting serum TG was reported for participants with elevated baseline fasting TG (>200 mg/dL) in Cohort B and Cohorts A + B.
Measured: Baseline to week 12
Change From Baseline to Week 12 in HbA1c (Cohorts B and A + B)
Change in HbA1c was reported for participants with elevated baseline HbA1c (>7.0%) in Cohort B and Cohorts A + B.
Measured: Baseline to week 12
Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 1)
Percent change in fasting serum TG was reported for participants in Study Arm 1.
Measured: Baseline, Week 12, Week 24
Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 2)
Percent change in fasting serum TG was reported for participants in Study Arm 2.
Measured: Baseline, Week 12, Week 24
Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 1)
Change from baseline in HbA1c was reported for participants in Study Arm 1.
Measured: Baseline, Week 12, Week 24
Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 2)
Change from baseline in HbA1c was reported for participants in Study Arm 2.
Measured: Baseline, Week 12, Week 24
Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 1)
Change from baseline in fasting glucose was reported for participants in Study Arm 1.
Measured: Baseline, Week 12, Week 24
Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 2)
Change from baseline in fasting glucose was reported for participants in Study Arm 2.
Measured: Baseline, Week 12, Week 24
Percent Change From Baseline to Weeks 12 and 24 in Liver Fat Magnetic Resonance Imaging-derived Proton Density Fat Fraction (MRI-PDFF) (Study Arm 1)
Percent change from baseline in MRI-PDFF was reported for participants with baseline MRI-PDFF ≥8.5% in Study Arm 1.
Measured: Baseline, Week 12, Week 24
Percent Change From Baseline to Weeks 12 and 24 in Liver Fat MRI-PDFF (Study Arm 2)
Percent change from baseline in MRI-PDFF was reported for participants with baseline liver fat MRI-PDFF ≥8.5% in Study Arm 2.
Measured: Baseline, Week 12, Week 24
Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score
The daily lipodystrophy hunger questionnaire was developed to assess hunger related behaviors among patients with lipodystrophy. The highest hunger score asked participants to rate their highest hunger that day on a scale from 0 to 4, with higher scores representing the higher perceived hunger. A negative change from baseline indicated a reduction in perceived hunger.
Measured: Baseline, Week 12, Week 24
Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score
The daily lipodystrophy hunger questionnaire was developed to assess hunger related behaviors among patients with lipodystrophy. The lowest hunger score asked participants to rate their lowest hunger that day on a scale from 0 to 4, with higher scores indicating higher perceived hunger. A negative change from baseline score indicated a reduction in perceived lowest hunger.
Measured: Baseline, Week 12, Week 24
Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score
The daily lipodystrophy hunger questionnaire was developed to assess hunger related behaviors among participants with lipodystrophy. The felt hungry score asked how much time participants felt hunger that day on a scale from 0 to 4, with higher scores indicating more time feeling hungry. A negative change from baseline score indicated a reduction in time spent feeling hungry.
Measured: Baseline, Week 12, Week 24
Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score
The daily lipodystrophy hunger questionnaire was developed to assess hunger related behaviors among patients with lipodystrophy. The fullness score asked participants to rate how often they felt full after eating that day on a scale from 0 to 4, with higher scores indicating higher feeling of fullness. A negative change from baseline indicated a reduced feeling of fullness.
Measured: Baseline, Week 12, Week 24
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Measured: Up to Day 169
Concentrations of REGN4461 in Serum
Measured: Weeks 0, 1, 2, 3, 4, 5, 6, 9, 12, 13, 14, 15, 16, 17, 18, 21, 28, 32 and 36. Weeks 0 and 12 collected pre- and post-dose. All other time points were only pre-dose.
Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Response
Measured: Up to Day 281
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2021
- Study start28 Feb 2022
- Primary completion13 Dec 2023
- Study completion18 Apr 2024
Why it stopped: Sponsor Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Familial Partial LipodystrophyStudies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05088460
- Sponsor's protocol ID
- R4461-PLD-20100
- Other IDs
- 2021-000138-33
- Acronym
- LEAP
- Status last verified
- Aug 2025
- First submitted
- 12 Oct 2021
- Last updated
- 16 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-Blind Placebo-Controlled Study of the LEPR Agonist Antibody REGN4461 for the Treatment of Metabolic Abnormalities in Patients With Familial Partial Lipodystrophy
- ClinicalTrials.gov ID
- NCT05088460
- Acronym / sponsor ID
- LEAP / R4461-PLD-20100
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor Decision
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 28 Feb 2022 (actual)
- Primary completion
- 13 Dec 2023 (actual)
- Study completion
- 18 Apr 2024 (actual)
- First posted
- 22 Oct 2021 (actual)
- Results
- Posted 2 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Two cohorts are being studied based on leptin levels. Cohort A is composed of patients with baseline leptin <8.0 ng/mL and Cohort B is composed of patients with baseline leptin 8.0 to ≤20.0 ng/mL
The primary objectives will be evaluated for patients in Cohort A only:
- To evaluate the effect of REGN4461 on fasting triglycerides (TG) in patients with elevated baseline fasting TG
- To evaluate the effect of REGN4461 on hyperglycemia in patients with elevated baseline Hemoglobin A1c (HbA1c)
The following secondary objectives of the study will be evaluated for Cohort B and for the combined set of Cohorts A plus B:
- To evaluate the effect of REGN4461 on fasting TG levels in patients with hypertriglyceridemia
- To evaluate the effect of REGN4461 on glycemic control in patients with hyperglycemia
The following secondary objectives of the study will be evaluated for Cohorts A and B separately, and for the combined set of Cohorts A plus B:
- To evaluate the effect of REGN4461 on liver fat in patients with hepatic steatosis
- To evaluate the effect of REGN4461 on hunger
- To evaluate safety and tolerability of REGN4461
- To characterize the concentration profile of REGN4461 over time
- To assess immunogenicity to REGN4461
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study Arm 1 | Experimental | Drug: REGN4461, Drug: Matching PlaceboRandomized to placebo for 12 weeks and then crossover to REGN4461 for 12 weeks |
| Study Arm 2 | Experimental | Drug: REGN4461Randomized to receive REGN4461 for 24 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Clinical diagnosis of familial partial lipodystrophy as defined in the protocol
- Fasting leptin level ≤20.0 ng/ml, as determined during the screening period
- Presence of significant metabolic abnormalities related to glucose and triglycerides (TGs) as defined in the protocol
- Stable body weight within the 3 months prior to screening (no gain or loss of >5% current weight)
- Stable diet during the past 3 months defined as no major change in macronutrient composition (eg, starting or stopping diets such as Atkins, Paleo, Vegetarianism, Veganism)
Key exclusion criteria (5 listed)
- Treatment with metreleptin within 3 months of the screening visit
- Patients with a diagnosis of generalized lipodystrophy
- Patients with a diagnosis of acquired lipodystrophy
- Pregnant or breastfeeding women
- NOTE: Other protocol defined inclusion/exclusion criteria apply
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| REGN4461Also: mibavademabIntravenous (IV) infusion loading dose followed by subcutaneous (SC) injection weekly (QW). | Drug | Study Arm 1, Study Arm 2 |
| Matching PlaceboIntravenous (IV) infusion loading dose followed by subcutaneous (SC) injection weekly (QW). | Drug | Study Arm 1 |
Primary outcome
Percent Change From Baseline to Week 12 in Fasting Serum Triglyceride (TG) (Cohort A)
Time frame: Baseline to week 12
Percentage change in fasting serum TG was reported for participants with elevated baseline fasting TG (> 200 mg/dL) and with baseline leptin < 8.0 ng/mL (Cohort A).
Change From Baseline to Week 12 in Hemoglobin A1c (HbA1c) (Cohort A)
Time frame: Baseline to week 12
Change in HbA1c was reported for participants with elevated baseline HbA1c (> 7.0%) and with baseline leptin < 8.0 ng/mL (Cohort A).
17 secondary outcomes
Percent Change From Baseline to Week 12 in Fasting Serum TG (Cohorts B and A + B)
Time frame: Baseline to week 12
Change From Baseline to Week 12 in HbA1c (Cohorts B and A + B)
Time frame: Baseline to week 12
Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 1)
Time frame: Baseline, Week 12, Week 24
Percent Change From Baseline to Weeks 12 and 24 in Fasting Serum TG (Study Arm 2)
Time frame: Baseline, Week 12, Week 24
Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 1)
Time frame: Baseline, Week 12, Week 24
Change From Baseline to Weeks 12 and 24 in HbA1c (Study Arm 2)
Time frame: Baseline, Week 12, Week 24
Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 1)
Time frame: Baseline, Week 12, Week 24
Change From Baseline to Weeks 12 and 24 in Fasting Glucose (Study Arm 2)
Time frame: Baseline, Week 12, Week 24
Percent Change From Baseline to Weeks 12 and 24 in Liver Fat Magnetic Resonance Imaging-derived Proton Density Fat Fraction (MRI-PDFF) (Study Arm 1)
Time frame: Baseline, Week 12, Week 24
Percent Change From Baseline to Weeks 12 and 24 in Liver Fat MRI-PDFF (Study Arm 2)
Time frame: Baseline, Week 12, Week 24
Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Highest Hunger Score
Time frame: Baseline, Week 12, Week 24
Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Lowest Hunger Score
Time frame: Baseline, Week 12, Week 24
Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Felt Hungry Score
Time frame: Baseline, Week 12, Week 24
Change From Baseline to Weeks 12 and 24 on the Daily Lipodystrophy Hunger Questionnaire - Fullness Score
Time frame: Baseline, Week 12, Week 24
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to Day 169
Concentrations of REGN4461 in Serum
Time frame: Weeks 0, 1, 2, 3, 4, 5, 6, 9, 12, 13, 14, 15, 16, 17, 18, 21, 28, 32 and 36. Weeks 0 and 12 collected pre- and post-dose. All other time points were only pre-dose.
Number of Participants With Treatment-emergent Anti-drug Antibody (ADA) Response
Time frame: Up to Day 281
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Summary is available on TrialSummaries.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trial Management study director
Regeneron Pharmaceuticals
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing REGN4461 in people with Familial Partial Lipodystrophy and Metabolic Abnormalities, run by Regeneron Pharmaceuticals at 8 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, France, Spain, Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline to Week 12 in Fasting Serum Triglyceride (TG) (Cohort A) (time frame: Baseline to week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2025.