Targeting Beta Cell Dysfunction With Liraglutide or Golimumab in Longstanding T1D

Carla Greenbaum, MD

Status and phase: Completed; Early Phase 1

Conditions: Type 1 Diabetes Mellitus

Treatments: Drug: Liraglutide; Drug: Golimumab

Study type: Interventional

Funder types: Other

Identifiers

NCT03632759

IRB18-044

Details and patient eligibility

About

The purpose of this study is to determine whether 8 weeks of Liraglutide or Golimumab can transiently improve beta cell function in patients with longstanding Type 1 diabetes (T1D) who secrete proinsulin and little/no C-peptide.

Enrollment: 16 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. ≥ 3 years from Type 1 diabetes diagnosis
2. Males and females 18-50 years of age, inclusive
3. Peak MMTT stimulated C-peptide <0.017 pmol/mL
4. Proinsulin levels ≥ 2 pM (either fasting or stimulated)
5. Females of child-bearing potential must be willing to use effective birth control for 12 weeks
6. Willing and able to give informed consent for participation
7. HbA1c ≤ 8.5%

Exclusion criteria

1. Concurrent use of non-insulin therapies aimed to control hyperglycemia or use within the past 30 days of screening MMTT (V-2).

2. History of severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies.

3. Diagnosis of liver disease or elevated hepatic enzymes, as defined by ALT or AST> 1.5 x the upper limit of age-determined normal (ULN) .

4. Females who are pregnant or lactating.

5. Receipt of an immune modulating biologic or investigational drug within 3 months or 5 half-lives before enrollment.

6. History of other clinically significant autoimmune disease needing chronic therapy with biologics or steroids with the exception of celiac and stable thyroid disease.

7. Current use of any medication known to significantly influence glucose tolerance (e.g. oral steroids, atypical antipsychotics, diphenylhydantoin, niacin).

8. Any medical or psychological condition that in the opinion of the principal investigator would interfere with the safe completion of the trial.

9. For Study A (liraglutide)

   1. Any history of pancreatitis or elevated amylase or lipase.
   2. Any personal or family history of thyroid C-cell tumors, including medullary thyroid carcinoma (MTC).
   3. Any personal or family history of multiple endocrine neoplasia syndrome type 2.
   4. Hypersensitivity to liraglutide.
   5. Previous treatment with liraglutide.
   6. Known history of clinically significant gastroparesis.

10. For Study B (golimumab)

    1. Any history of recent (within 3 months) serious bacterial, viral, fungal, or other opportunistic infections.

    2. Any history of demyelinating diseases (such as multiple sclerosis), heart failure, or left ventricular dysfunction.

    3. Serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C.

    4. Positive QuantiFERON or PPD TB test, history of tuberculosis, or active TB infection.

    5. Active infection with EBV, defined by real-time PCR.

    6. Active infection with CMV, defined by real-time PCR.

    7. Any of the following hematologic abnormalities at screening:

       • White blood count <3,000/μL or >14,000/μL
       • Lymphocyte count <500/μL
       • Platelet count <140,000 /μL
       • Hemoglobin <8.5 g/dL
       • Neutrophil count <2,000 cells/μL

    8. Receipt of live vaccine (in the 6 weeks before treatment)

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

16 participants in 2 patient groups

Liraglutide

Experimental group

Description:

Participants will receive subcutaneous (SC) liraglutide for 8 weeks

Treatment:

Drug: Liraglutide

Golimumab

Experimental group

Description:

Participants will receive subcutaneous (SC) golimumab for 8 weeks

Treatment:

Drug: Golimumab