Generalized LipodystrophyPhase 2NCT04159415
Study of REGN4461, a Leptin Receptor Agonist Antibody, in Patients With Generalized Lipodystrophy
A Phase 2 study testing Low-Dose REGN4461 and High-dose REGN4461 in people with Generalized Lipodystrophy, run by Regeneron Pharmaceuticals at 8 sites in 4 countries.
Trial summary
The primary objectives of the study are to estimate the effects of REGN4461 on glycemic parameters in the subset of patients with elevated baseline hemoglobin A1c levels (HbA1c ≥7%) and to estimate the effects of REGN4461 on fasting triglyceride levels in the subset of patients with elevated baseline fasting… Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Generalized Lipodystrophy
- What is being tested?
- Low-Dose REGN4461 and High-dose REGN4461
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 8 sitesin 4 countries
- Study dates
- 7 Jan 2020to 24 Sep 2024
- Phase
- Phase 2
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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of congenital or acquired generalized lipodystrophy (GLD), as defined in the protocol
- Presence of one or both of the following metabolic abnormalities at screening:
- HbA1c ≥ 7% OR
- Fasting TG ≥250 mg/dL
- Generally stable diet (based on patient's recall) and medication regimen (that optimizes treatment for their metabolic disease) for at least 3 months prior to the screening visit
Who cannot join
- Treatment with metreleptin within 1 month of the screening visit
- Treatment with over-the-counter or prescription medications for weight loss within 3 months prior to the screening visit
- Treatment with oral glucocorticoids >7.5 mg prednisone equivalents per day within 3 months prior to screening visit or plans to begin treatment with oral glucocorticoids >7.5 mg prednisone equivalents per day during the study period
- History of Human Immunodeficiency Virus (HIV) or HIV seropositivity at screening visit
- Uncontrolled infection with hepatitis B or hepatitis C infection, or known active tuberculosis at screening
- Participation in any clinical research study evaluating an Investigational product (IP) or therapy within 3 months and less than 5 half-lives of IP prior to the screening visit.
- Pregnant or breast-feeding women
- NOTE: Other protocol defined inclusion/exclusion criteria apply.
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
United States3 sites
Regeneron Research Site
Ann Arbor, Michigan, 48105
Regeneron Research Site
Bethesda, Maryland, 20892
Regeneron Research Site
Dallas, Texas, 75390
Turkey (Türkiye)3 sites
Regeneron Research Site
Ankara, 06230
Regeneron Research Site
Diyarbakır, 21808
Regeneron Research Site
Izmir, 35100
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Study of REGN4461, a Leptin Receptor Agonist Antibody, in Patients With Generalized Lipodystrophy
The primary objectives of the study are to estimate the effects of REGN4461 on glycemic parameters in the subset of patients with elevated baseline hemoglobin A1c levels (HbA1c ≥7%) and to estimate the effects of REGN4461 on fasting triglyceride levels in the subset of patients with elevated baseline fasting triglycerides (TG ≥250 mg/dL).
The secondary objectives are to estimate the effects of REGN4461 on a composite endpoint of changes in either HbA1c or fasting TG for all patients, estimate the effects of 3 dose levels of REGN4461 on glycemic parameters and fasting TG, to estimate the effects of REGN4461 on insulin sensitivity, to evaluate the safety and tolerability of REGN4461 and to evaluate the pharmacokinetics (PK) and immunogenicity of REGN4461.
- Conditions
- Generalized Lipodystrophy
- Being tested
- Placebo, Low-Dose REGN4461, High-dose REGN4461
- Medical subject headings
- Lipodystrophy, Congenital Generalized
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Intravenous (IV) infusion loading dose or subcutaneous (SC) injection weekly (QW).
Low-Dose REGN4461Drug
Also called mibavademab
IV infusion loading dose or SC injection QW.
High-dose REGN4461Drug
Also called mibavademab
IV infusion loading dose or SC injection QW.
| Study group | Role | What they receive |
|---|---|---|
| Treatment A | Experimental | Not described Receives: Drug: Placebo; Drug: Low-Dose REGN4461; Drug: High-dose REGN4461 |
| Treatment B | Experimental | Not described Receives: Drug: Placebo; Drug: Low-Dose REGN4461; Drug: High-dose REGN4461 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute Change From Baseline in Participants With Elevated Baseline Hemoglobin A1c (HbA1c ≥7%) at Week 8
Absolute change from baseline in HbA1c for subgroup of participants with baseline HbA1c ≥7% reported
Measured: Baseline, Week 8
Absolute Change From Baseline in Fasting Glucose at Week 8
Absolute change from baseline in fasting glucose for subgroup of participants with baseline HbA1c ≥7% reported
Measured: Baseline, Week 8
Absolute Change From Baseline in Weighted Mean Glucose (WMG) at Week 8
Absolute change from baseline in WMG for subgroup of participants with baseline HbA1c ≥7% reported
Measured: Baseline, Week 8
Percent Change From Baseline in Fasting Triglycerides (TG) at Week 8
Percent change from baseline in participants with elevated baseline fasting TG (fasting TG ≥250 mg/dL) reported
Measured: Baseline, Week 8
Secondary outcomes (18)
Absolute Change From Baseline in HbA1c and Fasting TG Composite Endpoint at Week 8
The composite score is calculated for each individual participant using baseline and Week 8 measurements of HbA1c and fasting TG.
For each participant, a Z-score is calculated separately for HbA1c and fasting TG, rescaling the change from baseline based on the standard deviation of the baseline value for all participants, as a way of standardizing the change value.
The composite score uses one or both of the calculated Z-scores depending on which parameters were abnormal at baseline. If both, then the participant's composite is the average of the two parameter Z-scores.
At the participant level, a Z-score of zero for either parameter indicates no change in that metabolic parameter, but a composite Z-score of zero can also reflect offsetting changes in metabolic parameters. A negative Z-score would be interpreted as an overall improvement in metabolic function, but a negative Z-score can also result from a decrease in one parameter not being canceled by an increase in the other.
Measured: Baseline, Week 8
Absolute Change From Baseline in Fasting Glucose
Measured: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52
Absolute Change From Baseline in Fasting Glucose for Participants With Baseline HbA1c ≥7%
Measured: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52
Percent Change From Baseline in Fasting TG
Measured: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52
Percent Change From Baseline in Fasting TG for Participants With Baseline Fasting TG ≥250 mg/dL
Measured: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 4, 12, 24, 52
Absolute Change From Baseline in HbA1c
Measured: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 12, 24, 52
Absolute Change From Baseline in HbA1c for Participants With Baseline HbA1c ≥7%
Measured: Baseline, Weeks 16, 24, 36, 52; OLTP 5 Weeks 12, 24, 52
Absolute Change From Baseline in Weighted Mean Glucose (WMG)
Measured: Baseline, Weeks 16 and 24
Absolute Change From Baseline in WMG for Participants With Baseline Fasting HbA1c ≥7%
Measured: Baseline, Weeks 16 and 24
Change From Baseline in Glucose Area Under the Concentration-time Curve (AUC0-4) During a Mixed Meal Tolerance Test (MMTT)
Measured: Baseline, Weeks 8, 16, 24
Change From Baseline in Glucose AUC0-4 During a MMTT for Participants With Baseline HbA1c ≥7%
Measured: Baseline, Weeks 8, 16, 24
Change From Baseline in Glucose Infusion Rate Per Kilogram (kg) Body Mass During Hyperinsulinemia-euglycemic Clamp
Measured: Baseline, Weeks 8 and 52
Change From Baseline in Glucose Infusion Rate Per kg Body Mass During Hyperinsulinemia-euglycemic Clamp for Participants With Baseline HbA1c ≥7%
Measured: Baseline, Weeks 8 and 52
Change From Baseline in Glucose Clearance Rate (kITT) During Insulin-tolerance Test (ITT)
Measured: Baseline, Weeks 8 and 52
Change From Baseline in Glucose kITT During ITT for Participants With Baseline HbA1c ≥7%
Measured: Baseline, Weeks 8 and 52
Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE)
Measured: From first dose of DBTP study treatment through last dose of OLTP 5 study treatment plus 16 weeks (approximately 120 weeks)
Concentrations of Total REGN4461 in Serum Over Time
Measured: Weeks 0 (post-dose), 8, 16 (post-dose), 36, 52; OLTP 5 Weeks 4, 12, 24, 52
Number of Participants With Anti-drug Antibodies (ADA) to REGN4461
Measured: Approximately Week 128
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2019
- Study start7 Jan 2020
- Primary completion5 Jan 2022
- Study completion24 Sep 2024
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 Generalized 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
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 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
- NCT04159415
- Sponsor's protocol ID
- R4461-GLD-1875
- Other IDs
- 2019-000614-11, 2019
- Status last verified
- May 2026
- First submitted
- 7 Nov 2019
- Last updated
- 15 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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