A Study to Determine Safety and Efficacy of (REMD-477) in Controlling Hyperglycemia Due to Copanlisib

Study Overview
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Brief Summary
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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

Official Title
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A Phase I/Ib Pilot Study to Determine the Safety and Efficacy of a Human Anti-glucagon Receptor Antibody (REMD-477) in Controlling Severe Hyperglycemia Due to Copanlisib in Patients With Relapsed or Refractory Lymphoma

Conditions
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Hyperglycemia Drug Induced

Intervention / Treatment
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* Biological: REMD-477


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: REMD-477<br>REMD-477 (human IgG2 anti-glucagon receptor antibody Volagidemab) will be administered as a subcutaneous injection for three weekly doses | Biological: REMD-477<br>* REMD-477 will be administered as a subcutaneous injection for three weekly doses<br>* Other names: Volagidemab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase inhibitor | 22 days | 
| Serious Adverse Events | Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase | 22 days | 
| Liver Function Tests (LFT) units per liter (u/L) | Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase | 22 days | 
| Blood Glucose measurements | Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase | 22 days | 
| Pulse beats per minute | Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase | 22 days | 
| breathing Rate breaths per minute | Evaluate the safety of REMD-477 in patients with hyperglycemia due to a PI3 kinase | 22 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Glucose levels | Determine efficacy of REMD-477 in preventing copanlisib induced hyperglycemia | 22 days | 
| Insulin levels | Determine efficacy of REMD-477 in preventing copanlisib induced hyperglycemia | 22 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyperglycemia, lymphoma, anti-glucagon receptor antibody, glucagon receptor, Volagidemab