Volagidemab for Low Blood Sugar in Type 1 Diabetes

Recruiting at 2 trial locations

Overseen By Edgar Bautista

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: REMD Biotherapeutics, Inc.

Must be taking: Insulin

Must not be taking: Antihyperglycemics, Corticosteroids

Disqualifiers: Type 2 diabetes, Pancreatitis, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 9

Duration: 6 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is designed to evaluate the effect of glucagon receptor antagonism by volagidemab (once weekly) on glucose recovery from hypoglycemia after treatment with glucagon in adults with type 1 diabetes. After informed consent, Screening procedures to establish subject eligibility will be performed within a period of 28 days. Approximately 24 subjects with type 1 diabetes mellitus (T1DM) on stable doses of insulin will be enrolled. After enrollment, subjects will undergo a baseline Hypoglycemia Recovery Procedure (with glucagon rescue). Subjects will then receive volagidemab subcutaneously (SC) once weekly for 6 weeks. At the end of the treatment phase, subjects will undergo a second Hypoglycemia Recovery Procedure. Subjects will be followed for 6 weeks after the last volagidemab dose with a final End-of-Study (EOS) visit during Week 12. The primary outcome will be the change in time to glucagon treatment success at Week 6 versus baseline.

Will I have to stop taking my current medications?

The trial requires that participants with type 1 diabetes stop taking any other antihyperglycemic drugs (medications that lower blood sugar) at least 30 days before starting the study. If you are on such medications, you will need to stop them to participate.

Is Volagidemab safe for humans?

Volagidemab, also known as REMD-477, has been tested in people with type 1 diabetes and showed no increase in low blood sugar events, but some increases in liver enzymes, cholesterol, and blood pressure were noted. Overall, it was considered to have a tolerable safety profile, suggesting it is generally safe for humans, though further studies are needed to confirm long-term safety. ^{1 2 3 4 5}

How does the drug Volagidemab work for low blood sugar in type 1 diabetes?

Volagidemab is unique because it is a monoclonal antibody that blocks the glucagon receptor, which helps reduce the need for insulin and improves blood sugar control in people with type 1 diabetes. Unlike other treatments, it specifically targets glucagon, a hormone that raises blood sugar levels, making it a novel approach to managing this condition. ^{2 3 5 6 7}

What data supports the effectiveness of the drug Volagidemab for low blood sugar in type 1 diabetes?

Research shows that Volagidemab, a drug that blocks glucagon action, helped reduce daily insulin use and improved blood sugar control in people with type 1 diabetes. Although the main goal of the study wasn't fully met, the drug did lower a key blood sugar marker (HbA1c) and was generally safe, suggesting it could be helpful with more research. ^{2 3 6 8 9}

Who Is on the Research Team?

Zung Thai, MD

Principal Investigator

REMD Biotherapeutics

Are You a Good Fit for This Trial?

This trial is for adults with Type 1 Diabetes who are on stable insulin doses. They must be able to give informed consent and go through a screening process within 28 days before starting the trial. People with other health conditions that could interfere with the study or those unable to follow its procedures may not qualify.

Inclusion Criteria

HbA1c less than or equal to 10.0%

Currently using a continuous glucose monitoring (CGM) system

My BMI is between 18.5 and 35.

Exclusion Criteria

I have a history of type 2 diabetes, MODY, pancreatic surgery, or chronic pancreatitis.

I haven't taken any diabetes medication other than insulin in the last 30 days.

I've had a severe low blood sugar episode that needed hospital care in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Baseline Hypoglycemia Recovery Procedure

Subjects undergo a baseline Hypoglycemia Recovery Procedure with glucagon rescue

1 day

1 visit (in-person)

Treatment

Participants receive volagidemab subcutaneously once weekly for 6 weeks

6 weeks

6 visits (in-person)

Second Hypoglycemia Recovery Procedure

Subjects undergo a second Hypoglycemia Recovery Procedure at the end of the treatment phase

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Volagidemab

Trial Overview The trial tests how well volagidemab, given once weekly by injection, helps recover from low blood sugar when treated with glucagon in people with Type 1 Diabetes. It involves initial and final hypoglycemia recovery procedures over a span of 12 weeks.

How Is the Trial Designed?

Group I: 35 mg Volagidemab Experimental Treatment 1 Intervention

Volagidemab 35 mg will be administered by subcutaneous (SC) injection once weekly for 6 weeks.

Who Is Running the Clinical Trial?

REMD Biotherapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

320+

Published Research Related to This Trial

In a phase 2 study involving 79 adults with type 1 diabetes, the monoclonal antibody volagidemab showed a significant reduction in hemoglobin A1c (HbA1c) levels compared to placebo, indicating improved glycemic control.

Volagidemab also led to a decrease in daily insulin use without increasing the risk of hypoglycemia, although some side effects like increased serum transaminases and LDL-cholesterol were noted, suggesting a need for further studies on its long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon receptor antagonist volagidemab in type 1 diabetes: a 12-week, randomized, double-blind, phase 2 trial. Pettus, J., Boeder, SC., Christiansen, MP., et al.[2023]

In a clinical trial with 21 patients, a single dose of REMD-477, a glucagon receptor antagonist, significantly reduced insulin use by 26% one day after administration compared to placebo, indicating its potential to lower insulin requirements in type 1 diabetes.

REMD-477 also improved glycaemic control, resulting in an average daily glucose level that was 27 mg/dL lower and increased time spent in the target glucose range, without causing any serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a glucagon receptor antibody (REMD-477) in type 1 diabetes: A randomized controlled trial. Pettus, J., Reeds, D., Cavaiola, TS., et al.[2020]

This study will evaluate the effects of the GLP-1 analogue liraglutide on pancreatic β-cell function in young individuals (ages 10-30) with early stages of type 1 diabetes, including those with multiple islet autoantibodies, over a 6-month period with follow-ups ranging from 6 to 18 months.

Liraglutide aims to support β-cell health and potentially reduce islet autoimmunity, contrasting with most prevention trials that focus solely on the immune system, thus providing a novel approach to managing early type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

INnoVative trial design for testing the Efficacy, Safety and Tolerability of 6-month treatment with incretin-based therapy to prevent type 1 DIAbetes in autoantibody positive participants: A protocol for three parallel double-blind, randomised controlled trials (INVESTDIA). Kero, J., Koskenniemi, JJ., Karsikas, S., et al.[2022]

In a study involving 45 adults with type 1 diabetes, liraglutide did not significantly alter the glucagon response to hypoglycemia after 4 weeks of treatment, indicating that it does not compromise the body's ability to respond to low blood sugar levels.

Participants treated with liraglutide experienced greater reductions in insulin dosage and body weight compared to those on placebo, suggesting potential benefits in managing diabetes without negatively affecting hypoglycemic responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Counter-regulatory hormone responses to hypoglycaemia in people with type 1 diabetes after 4 weeks of treatment with liraglutide adjunct to insulin: a randomized, placebo-controlled, double-blind, crossover trial. Pieber, TR., Deller, S., Korsatko, S., et al.[2022]

In a phase 2 clinical trial involving 58 participants with recent-onset type 1 diabetes, treatment with antithymocyte globulin (ATG) did not preserve β-cell function compared to placebo after 12 months, indicating it may not be an effective treatment for this condition.

While ATG treatment led to significant T-cell depletion and associated adverse events, it did not result in a difference in the incidence of infections between the ATG and placebo groups, suggesting that the safety profile may be concerning due to the high rate of severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antithymocyte globulin treatment for patients with recent-onset type 1 diabetes: 12-month results of a randomised, placebo-controlled, phase 2 trial. Gitelman, SE., Gottlieb, PA., Rigby, MR., et al.[2021]

Dasiglucagon significantly reduces the recovery time for blood glucose levels in patients with type 1 diabetes experiencing severe hypoglycemia, outperforming both traditional glucagon and placebo in clinical trials involving 347 patients.

The safety profile of dasiglucagon is comparable to that of native glucagon, suggesting it is a safe option for treating severe hypoglycemia in type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of dasiglucagon in severe hypoglycemia associated with patients of type 1 diabetes mellitus: a systematic review and meta-analysis. Dholariya, S., Parchwani, D., Dutta, S., et al.[2023]

GLP-1 receptor agonists (like exenatide and liraglutide) can significantly lower hemoglobin A1C levels, plasma glucose, and body weight in patients with type 1 diabetes who are already on insulin, without increasing the risk of hypoglycemia.

The most common side effects of GLP-1 RAs are mild and transient gastrointestinal issues, making them a safe option for patients struggling with insulin side effects or those needing to lose weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive Role of Glucagon-Like Peptide-1 Receptor Agonists in the Management of Type 1 Diabetes Mellitus. Harris, KB., Boland, CL.[2022]

In a trial with 112 subjects with type 1 diabetes, dasiglucagon showed no incidence of antidrug antibodies (ADA) after three weekly subcutaneous doses, indicating a strong safety profile and low immunogenicity.

No injection site reactions or unexpected safety issues were reported, suggesting that dasiglucagon is a safe option for treating severe hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity of the Novel Glucagon Analogue Dasiglucagon: Results of a Dedicated Immunogenicity Trial in Type 1 Diabetes. Pieber, TR., Ajala, O., Steen, O., et al.[2022]

A phase 3 study is investigating the effectiveness of intralymphatic administration of rhGAD65 in preserving insulin secretion and improving blood sugar control in young individuals recently diagnosed with Type 1 diabetes who carry the HLA DR3-DQ2 haplotype, involving 330 participants and a follow-up period of 22 months.

Previous phase 2b studies showed that rhGAD65 could help maintain insulin production, suggesting it may be a promising therapy to halt the autoimmune destruction of insulin-producing cells in Type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III, randomised, double-blind, placebo-controlled, multicentre trial to evaluate the efficacy and safety of rhGAD65 to preserve endogenous beta cell function in adolescents and adults with recently diagnosed type 1 diabetes, carrying the genetic HLA DR3-DQ2 haplotype: the DIAGNODE-3 study protocol. Ludvigsson, J., Eriksson, L., Nowak, C., et al.[2022]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Glucagon receptor antagonist volagidemab in type 1 diabetes: a 12-week, randomized, double-blind, phase 2 trial. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Effect of a glucagon receptor antibody (REMD-477) in type 1 diabetes: A randomized controlled trial. [2020]

3. England pubmed.ncbi.nlm.nih.gov

INnoVative trial design for testing the Efficacy, Safety and Tolerability of 6-month treatment with incretin-based therapy to prevent type 1 DIAbetes in autoantibody positive participants: A protocol for three parallel double-blind, randomised controlled trials (INVESTDIA). [2022]

4. England pubmed.ncbi.nlm.nih.gov

Counter-regulatory hormone responses to hypoglycaemia in people with type 1 diabetes after 4 weeks of treatment with liraglutide adjunct to insulin: a randomized, placebo-controlled, double-blind, crossover trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Antithymocyte globulin treatment for patients with recent-onset type 1 diabetes: 12-month results of a randomised, placebo-controlled, phase 2 trial. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of dasiglucagon in severe hypoglycemia associated with patients of type 1 diabetes mellitus: a systematic review and meta-analysis. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Adjunctive Role of Glucagon-Like Peptide-1 Receptor Agonists in the Management of Type 1 Diabetes Mellitus. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Immunogenicity of the Novel Glucagon Analogue Dasiglucagon: Results of a Dedicated Immunogenicity Trial in Type 1 Diabetes. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Phase III, randomised, double-blind, placebo-controlled, multicentre trial to evaluate the efficacy and safety of rhGAD65 to preserve endogenous beta cell function in adolescents and adults with recently diagnosed type 1 diabetes, carrying the genetic HLA DR3-DQ2 haplotype: the DIAGNODE-3 study protocol. [2022]