Volagidemab for Low Blood Sugar in Type 1 Diabetes
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: REMD Biotherapeutics, Inc.
No Placebo Group
Trial Summary
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.
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.
24579What 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.
12467Is 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.
34578Will 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.
Eligibility Criteria
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
I have been taking insulin for Type 1 diabetes for at least 2 years.
I have been on a consistent insulin treatment for at least 8 weeks.
Exclusion Criteria
I have a history of type 2 diabetes, MODY, pancreatic surgery, or chronic pancreatitis.
I've had a severe low blood sugar episode that needed hospital care in the last 3 months.
I have received a pancreas, pancreatic islet cells, or kidney transplant.
I haven't taken steroids in the last 30 days and don't plan to start during the study.
I have a liver condition.
I am experiencing symptoms of anemia.
I have a history of pancreatitis, pancreatic tumors, or MEN in my family.
I am not pregnant, nursing, or planning to become pregnant during the trial.
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: 35 mg VolagidemabExperimental Treatment1 Intervention
Volagidemab 35 mg will be administered by subcutaneous (SC) injection once weekly for 6 weeks.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Diablo Clinical ResearchWalnut Creek, CA
Altman Clinical and Translational Research InstituteSan Diego, CA
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Who is running the clinical trial?
REMD Biotherapeutics, Inc.Lead Sponsor
References
Antithymocyte globulin treatment for patients with recent-onset type 1 diabetes: 12-month results of a randomised, placebo-controlled, phase 2 trial. [2021]Type 1 diabetes results from T-cell-mediated destruction of β cells. Findings from preclinical studies and pilot clinical trials suggest that antithymocyte globulin (ATG) might be effective for reducing this autoimmune response. We assessed the safety and efficacy of rabbit ATG in preserving islet function in participants with recent-onset type 1 diabetes, and report here our 12-month results.
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]To investigate the effect of glucagon-like peptide 1 receptor agonist liraglutide on the counter-regulatory hormone response to hypoglycaemia in type 1 diabetes.
Adjunctive Role of Glucagon-Like Peptide-1 Receptor Agonists in the Management of Type 1 Diabetes Mellitus. [2022]Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used in combination with insulin to manage type 2 diabetes mellitus, and four agents are currently approved for this indication: exenatide, liraglutide, dulaglutide, and albiglutide. The distinctive properties of GLP-1 RAs-potential hemoglobin A1c (A1C) reduction, weight loss, potential to reduce insulin doses, and lower hypoglycemia risk-have made these agents potential treatment options for patients with type 1 diabetes mellitus (T1DM) as well. These positive effects are due to glucose-dependent insulin secretion, reduced glucagon secretion, increased satiety, and delayed gastric emptying. Patients with T1DM are unable to suppress glucagon during meals, which contributes to postprandial hyperglycemia and may be improved with GLP-1 therapy. In this review, we evaluated the available literature on the clinical efficacy and safety of GLP-1 RAs in patients with T1DM. We conducted a search of the PubMed (1966-May 2016) and Ovid (1946-May 2016) databases. Abstracts presented at the scientific and clinical sessions of the American Diabetes Association and the American Association of Clinical Endocrinologists were also searched. The references of the published articles were also reviewed to identify additional studies appropriate for inclusion. All identified articles published in English were evaluated. Studies were included if they evaluated the clinical use or safety of GLP-1 RAs in patients with T1DM. Twelve studies were included, with four evaluating exenatide, one evaluating exenatide extended release, and seven evaluating liraglutide. Both exenatide and liraglutide showed significant reductions in hemoglobin A1C, plasma glucose concentration, body weight, and insulin doses when administered to patients with T1DM already receiving insulin therapy, without increasing the occurrence of hypoglycemia. Adverse effects were mostly gastrointestinal in nature but were mild and transient. Patients who may benefit most are those experiencing adverse effects from insulin, those not at their A1C goal but hypoglycemia prevents insulin titration, and those who may benefit from weight loss.
Effect of a glucagon receptor antibody (REMD-477) in type 1 diabetes: A randomized controlled trial. [2020]The aim of the current study (Clinical trial reg. no. NCT02715193, clinicaltrials.gov) was to study the efficacy and safety of REMD-477, a glucagon receptor antagonist, in type 1 diabetes. This was a randomized controlled trial in which 21 patients with type 1 diabetes were enrolled. Glycaemic control and insulin use were evaluated in outpatient and inpatient settings, before and after a single 70-mg dose of REMD-477 (half-life 7-10 days) or placebo. Inpatient insulin use was 26% (95% CI, 47%, 4%) lower 1 day after dosing with REMD-477 than with placebo (P = .02). Continuous glucose monitoring during post-treatment days 6 to 12 showed that average daily glucose was 27 mg/dL lower (P 180 mg/dL) was ~40% lower (~4 h/d) (P = .001) in the REMD-477 group than in the placebo group, without a difference in percent time-in-hypoglycaemic-range (
Immunogenicity of the Novel Glucagon Analogue Dasiglucagon: Results of a Dedicated Immunogenicity Trial in Type 1 Diabetes. [2022]Dasiglucagon is a next-generation glucagon analogue that is stable in aqueous formulation. This dedicated immunogenicity trial to support use as rescue treatment for severe hypoglycemia was conducted to evaluate the immunogenicity of repeated subcutaneous doses of dasiglucagon in subjects with type 1 diabetes. A total of 112 subjects were randomized 1:1 to receive three subcutaneous weekly doses of either 0.6 mg dasiglucagon or 1.0 mg recombinant glucagon (GlucaGen®) according to a double-blind parallel-group trial design. Subjects were followed for 15 weeks, with a multitiered testing approach planned for assessment of antidrug antibody (ADA) formation. For the primary immunogenicity endpoint, the overall ADA incidence was zero, as no subject demonstrated any treatment-induced or treatment-boosted ADA response at any time point in this trial involving three consecutive weekly doses of trial drug. No injection site reactions were reported for subjects receiving dasiglucagon. There were no unexpected safety findings for the trial.
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]β-cell stress and dysfunction may contribute to islet autoimmunity and progression to clinical type 1 diabetes. We present a protocol of three randomised controlled trials assessing the effects of glucagon-like peptide 1 (GLP - 1) analogue liraglutide in three early stages of type 1 diabetes.
Glucagon receptor antagonist volagidemab in type 1 diabetes: a 12-week, randomized, double-blind, phase 2 trial. [2023]Hyperglucagonemia contributes to hyperglycemia in patients with type 1 diabetes (T1D); however, novel therapeutics that block glucagon action could improve glycemic control. This phase 2 study evaluated the safety and efficacy of volagidemab, an antagonistic monoclonal glucagon receptor (GCGR) antibody, as an adjunct to insulin therapy in adults with T1D. The primary endpoint was change in daily insulin use at week 12. Secondary endpoints included changes in hemoglobin A1c (HbA1c) at week 13, in average daily blood glucose concentration and time within target range as assessed by continuous blood glucose monitoring (CGM) and seven-point glucose profile at week 12, incidence of hypoglycemic events, the proportion of subjects who achieve HbA1c reduction of ≥0.4%, volagidemab drug concentrations and incidence of anti-drug antibodies. Eligible participants (n = 79) were randomized to receive weekly subcutaneous injections of placebo, 35 mg volagidemab or 70 mg volagidemab. Volagidemab produced a reduction in total daily insulin use at week 12 (35 mg volagidemab: -7.59 units (U) (95% confidence interval (CI) -11.79, -3.39; P = 0.040 versus placebo); 70 mg volagidemab: -6.64 U (95% CI -10.99, -2.29; P = 0.084 versus placebo); placebo: -1.27 U (95% CI -5.4, 2.9)) without meeting the prespecified significance level (P < 0.025). At week 13, the placebo-corrected reduction in HbA1c percentage was -0.53 (95% CI -0.89 to -0.17, nominal P = 0.004) in the 35 mg volagidemab group and -0.49 (95% CI -0.85 to -0.12, nominal P = 0.010) in the 70 mg volagidemab group. No increase in hypoglycemia was observed with volagidemab therapy; however, increases in serum transaminases, low-density lipoprotein (LDL)-cholesterol and blood pressure were observed. Although the primary endpoint did not meet the prespecified significance level, we believe that the observed reduction in HbA1c and tolerable safety profile provide a rationale for further randomized studies to define the long-term efficacy and safety of volagidemab in patients with T1D.
Clinical efficacy and safety of dasiglucagon in severe hypoglycemia associated with patients of type 1 diabetes mellitus: a systematic review and meta-analysis. [2023]This study was carried out to analyze the clinical safety and efficacy of dasiglucagon for the treatment of severe hypoglycemia in patients with type 1 diabetes mellitus (T1DM).
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]Type 1 diabetes (T1D) is an autoimmune disease leading to the destruction of the insulin-producing beta cells resulting in insulin deficiency and hyperglycaemic. Today, no approved therapy exists to halt this detrimental immunologic process. In a recent phase 2b study, intralymphatic administration of recombinant human glutamic acid decarboxylase 65 kDa (rhGAD65) adsorbed to Alhydrogel adjuvant to individuals recently diagnosed with T1D and carrying the HLA DR3-DQ2 haplotype showed promising results in preserving endogenous insulin secretion, confirming the results of a large meta-analysis of three randomised placebo-controlled trials of subcutaneous rhGAD65. The aim of the current precision medicine phase 3 study is to determine whether intralymphatic administration of rhGAD65 preserves insulin secretion and improves glycaemic control in presumed responder individuals with recently diagnosed T1D carrying HLA DR3-DQ2.