Hyperglycemia Drug Induced
Conditions
Keywords
hyperglycemia, lymphoma, anti-glucagon receptor antibody, glucagon receptor, Volagidemab
Brief summary
REMD-477 (Volagidemab) is a human anti-glucagon receptor antibody. Its proposed mechanism of action in controlling hyperglycemia is by blocking glucagon receptor (GCGR) signaling. In this way, it increases hepatic glucose uptake, decreases hepatic glycogenolysis and gluconeogenesis, increases glycogen synthesis, and ultimately decreases blood glucose levels. This protocol will test the hypotheses that REMD-477 is safe and tolerable in patients with severe hyperglycemia on copanlisib and that it decreases the risk of severe hyperglycemia in patients receiving copanlisib for relapsed refractory lymphoma
Interventions
BIOLOGICALREMD-477
REMD-477 will be administered as a subcutaneous injection for three weekly doses
Sponsors
Duke University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 or older * Relapsed or refractory lymphoma (Grade 1, 2, 3A) * Received 2 or more prior lines of systemic therapy for lymphoma * Experienced glucose \>250 mg/dL after copanlisib infusion for treatment of lymphoma
Exclusion criteria
* Evidence of histologic transformation * Follicular Lymphoma Grade 3B * Active CNS involvement by malignancy * Elevated AST or ALT \> 5x ULN at Screening * Unmanageable sensitivity to mammalian-derived drug preparations, or to humanized or human antibodies; managed sensitivities to agents such as obinutuzumab or rituximab or similar agents are not exclusionary * History of drug or alcohol abuse within the last 6 months * History or family history of pancreatic neuroendocrine tumors or multiple endocrine neoplasia * History or family history of pheochromocytoma * Other gastrointestinal, cardiac, renal and CNS (i.e. hypoglycemia unawareness) conditions specific to diabetes that would pose additional risk to subject's safety or interfere with the study evaluation, procedures or completion in the opinion of the treating physician. * Female subject is pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| breathing Rate breaths per minute | 22 days | Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase |
| Blood Glucose measurements | 22 days | Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase |
| Pulse beats per minute | 22 days | Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase |
| Adverse Events | 22 days | Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase inhibitor |
| Serious Adverse Events | 22 days | Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase |
| Liver Function Tests (LFT) units per liter (u/L) | 22 days | Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin levels | 22 days | Determine efficacy of REMD-477 in preventing copanlisib induced hyperglycemia |
| Fasting Glucose levels | 22 days | Determine efficacy of REMD-477 in preventing copanlisib induced hyperglycemia |
Countries
United States
Outcome results
None listed