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Protocol Details

A Randomized, Double-Blinded, Placebo-Controlled Study of REGN4661, A Leptin Receptor Agonist Antibody, In Patients with Generalized Lipodystrophy

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

20-DK-0079

Sponsoring Institute

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

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 12
Max Age: N/A

Referral Letter Required

Yes

Population Exclusion(s)

None

Special Instructions

Currently Not Provided

Keywords

Leptin receptor agonist antibody;
Leptin receptor;
Antibody;
Generalized Lipodystrophy

Recruitment Keyword(s)

None

Condition(s)

Generalized lipodystrophy

Investigational Drug(s)

REGN4461

Investigational Device(s)

None

Intervention(s)

Other: Placebo
Drug: REGN4461

Supporting Site

National Institute of Diabetes and Digestive and Kidney Diseases

Background:

Generalized lipodystrophy (GLD) is a very rare condition. A person with GLD has near-complete loss of adipose tissue, or body fat. GLD can lead to infertility, diabetes, liver disease, and other issues. Researchers want to see if a drug called REGN4461 can help.

Objective:

To determine if REGN4461 is safe and if it works to reduce blood sugar and triglyceride levels in the body.

Eligibility:

People ages 12 years and older with GLD

Design:

Participants will be screened with blood and urine tests, physical exam, and medical history. They will have an electrocardiogram. It records the heart s electrical activity.

Screening tests will be repeated during the study.

Participants will have at least 8 study visits. Each visit will last up to 4 days.

Participants will get a placebo and REGN4461 at different times during the study. These will be given by intravenous infusion and by injection under the skin. The drugs will be given at the study site or at home each week for 56 weeks. Blood will be taken weekly.

Participants will have imaging scans. They will complete questionnaires and keep a diary.

Participants will have a mixed meal tolerance test. They will eat a meal and have blood samples taken.

Participants may have a liver stiffness test. A mechanical pulse will spread through the liver.

Participants will have an insulin function test. It measures how well insulin in the body works. Participants may have an optional liver biopsy or gene test.

After treatment ends, participants will be monitored for 16 weeks.

Participation will last for 1.5 years.

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Eligibility

INCLUSION CRITERIA:

A patient must meet the following criteria to be eligible for inclusion in the study:

1. Male or female patients, greater than or equal to 12 years of age at the screening visit (or lower limit of age approved by Health Authority, EC, and IRB)

2. Clinical diagnosis of congenital or acquired GLD based on history, physical examination, body composition, and metabolic status.

3. Presence of one or both of the following metabolic abnormalities at screening:

a. HbA1c greater than or equal to 7%

OR

b. Fasting TG greater than or equal to 250 mg/dL

4. 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

5. Willing and able to comply with clinic visits and study-related procedures (Note: patients incapable of completing PRO assessments or unable to undergo MRI will not be excluded.)

6. Provide informed consent signed by study patient or legally acceptable representative

EXCLUSION CRITERIA:

A patient who meets any of the following criteria will be excluded from the study:

1. Treatment with metreleptin within 1 month of the screening visit

2. Patients with clinically significant hematologic abnormalities such as neutropenia, lymphopenia, or lymphadenopathy at screening

3. Treatment with over-the-counter or prescription medications for weight loss within 3 months prior to the screening visit

4. Any malignancy, eg, lymphoma, within the past 1 year, prior to screening visit except for fully treated basal cell or squamous epithelial cell carcinomas of the skin or carcinoma in situ of the cervix or anus

5. Estimated GFR of <30 mL/min/1.73 m(2) based on CKD-Epi equation at screening

6. History of heart failure hospitalization, diagnosis of a myocardial infarction, stroke, transient ischemic attack, unstable angina, percutaneous or surgical revascularization procedure (coronary, carotid, or peripheral vascular), or intracardiac device placement (eg, pacemaker) within 3 months before the screening visit

7. Advanced heart failure (NYHA Class 3 to 4) or severe and uncontrolled hypertension at screening

8. History of HIV or HIV seropositivity at screening visit

9. Uncontrolled infection with hepatitis B or hepatitis C infection, or known active tuberculosis at screening

Patients will be tested for hepatitis C virus (HCV) and hepatitis B virus (HBV) at screening.

Patients with hepatitis B (HBVsAg+) who have controlled infection (serum HBV DNA PCR that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA per local standards. Patients must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug.

Patients who are hepatitis C virus antibody-positive (HCVAb+) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.

10. Patient has a history of an anaphylactic reaction to monoclonal antibody therapeutics or investigational products (IP)

11. Known hypersensitivity to doxycycline (or tetracycline class drugs) or excipients of the study drug formulation

12. Participation in any clinical research study evaluating an IP or therapy within 3 months and less than 5 half-lives of IP prior to the screening visit. Participation in clinical research studies that involve procedures (eg, muscle biopsies) or testing (eg, MRI) that will not interfere with the current study is permitted.

13. Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study

14. Pregnant or breast-feeding women

15. Women of childbearing potential (WOCBP)* who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 4 months after the last dose. Highly effective contraceptive measures include:

- Stable use of progestogen-containing hormonal contraception, or transdermal estrogen hormonal contraception, associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening

- Intrauterine device (IUD); intrauterine hormone-releasing system (IUS)

- Bilateral tubal ligation

- Vasectomized partner (provided that partner is the sole sexual partner of the WOCBP patient and that the vasectomized partner has received medical assessment of the surgical success)

- And/or sexual abstinence

* Women of child bearing potential is defined as women who are fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.

A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.

** Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drugs. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient.

*** Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception. Female condom and male condom should not be used together.

16. Sexually active adult or adolescent men who are unwilling to use the following forms of medically acceptable birth control during the study drug treatment period and for 4 months after the last dose of study drug: vasectomy with medical assessment of surgical success OR consistent use of a condom

Sperm donation is prohibited during the study and for 4 months after the last dose of study drug


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Citations:

Not Provided

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Contacts:

Principal Investigator

Referral Contact

For more information:

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



Megan S. Startzell, R.N.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institutes of Health
Building 10
Room 5-5750
10 Center Drive
Bethesda, Maryland 20892
(301) 402-6371
megan.startzell@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT04159415

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