Clinical trial NCT03117998: Multiple Dose Study to Evaluate the Efficacy, Safety and Pharmacodynamics of REMD-477 in Subjects With Type 1 Diabetes Mellitus
Official title: A Randomized, Placebo-controlled, Double-blind Study to Evaluate the Efficacy, Safety, and Pharmacodynamics of Multiple Doses of REMD-477 in Subjects With Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type1 Diabetes Mellitus
Lead sponsor: REMD Biotherapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2017-04-18
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, placebo-controlled, double-blind study to evaluate the efficacy, safety, and pharmacodynamics (PD) of multiple doses of REMD-477 in subjects who have Type 1 diabetes and are currently receiving insulin treatment. This study will determine whether REMD-477 can decrease daily insulin requirements and improve glycemic control after 12 weeks of treatment in subjects diagnosed with Type 1 diabetes with fasting C-peptide \< 0.7 ng/mL at Screening.

The study will be conducted at multiple sites in the United States. Approximately 150 subjects with type 1 diabetes on stable doses of insulin will be randomized in a 1:1:1 fashion into one of three treatment groups.


Eligibility criteria: Inclusion Criteria:

* Men and women between the ages of 18 and 65 years old, inclusive, at the time of screening;
* Females of non-child bearing potential must be ≥1 year post-menopausal (confirmed by a serum follicle-stimulating hormone (FSH) levels ≥ 40 IU/mL) or documented as being surgically sterile. Females of child bearing potential must agree to use two methods of contraception;
* Male subjects must be willing to use clinically acceptable method of contraception during the entire study;
* Body mass index between 18.5 and 32 kg/m2, inclusive, at screening;
* Diagnosed with Type 1 diabetes, based on clinical history or as defined by the current American Diabetes Association (ADA) criteria;
* HbA1c \> 7% and \< 10 % at screening;
* Fasting C-peptide \< 0.7 ng/mL;
* Treatment with a stable insulin regimen for at least 8 weeks before screening with multiple daily insulin (MDI) injections or continue subcutaneous insulin infusion (CSII)
* Willing to use continuous CGM system (e.g. DexCom) throughout the study;
* Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 1.5x upper limit of normal (ULN) at screening;
* Able to provide written informed consent approved by an Institutional Review Board (IRB).

Exclusion Criteria:

* History or evidence of clinically-significant disorder or condition that, in the opinion of the Investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion;
* Significant organ system dysfunction (e.g., clinically significant pulmonary or cardiovascular disease, anemia \[Hemoglobin \< 10.0 g/dL\], known hemoglobinopathies, and renal dysfunction \[eGFR \< 60 ml/min\]);
* Any severe symptomatic hypoglycemic event associated with a seizure or requiring help from other people or medical facility in the past 6 months;
* Myocardial infarction, unstable angina, revascularization procedure, or cerebrovascular accident ≤12 weeks before screening;
* History of New York Heart Association Functional Classification III-IV cardiac disease;
* Current or recent (within 1 month of screening) use of diabetes medications other than insulin - subjects on an SGLT2 inhibitor should be discontinue the SGLT2 inhibitor during the Screening Period, at least 2 weeks prior to the start of the Lead-in Period;
* Use of steroids and/or other prescribed or over-the-counter medications that are known to affect the outcome measures in this study or known to influence glucose metabolism;
* Smokes \> 10 cigarettes/day, and/or is unwilling to abstain from smoking during admission periods;
* Known sensitivity to mammalian-derived drug preparations, recombinant protein-based drugs or to humanized or human antibodies;
* History of illicit drug use or alcohol abuse within the last 6 months or a positive drug urine test result at screening;
* History of pancreatitis, pancreatic neuroendocrine tumors or multiple endocrine neoplasia (MEN) or family history of MEN;
* History of pheochromocytoma, or family history of familial pheochromocytoma;
* Known or suspected susceptibility to infectious disease (e.g. taking immunosuppressive agents or has a documented inherited or acquired immunodeficiency);
* Known history of positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HbsAg), or hepatitis C antibodies (HepC Ab);
* Participation in an investigational drug or device trial within 30 days of screening or within 5 times the half-life of the investigational agent in the other clinical study, if known, whichever period is longer;
* Blood donor or blood loss \> 500 mL within 30 days of Day 1;
* Women who are pregnant or lactating/breastfeeding;
* Unable or unwilling to follow the study protocol or who are non-compliant with screening appointments or study visits;
* Any other condition(s) that might reduce the chance of obtaining study data, or that might cause safety concerns, or that might compromise the ability to give truly informed consent

Other inclusion and exclusion criteria may apply.

Primary outcomes:
measure: Change in Average Daily Total Insulin Use
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Change From Baseline Difference in AUC Glucose Concentrations Following Mixed Meal Tolerance Test (MMTT) - Part A Only
timeFrame: Baseline and 13 weeks; AUC glucose timepoints: 10 minutes prior and just before (time ) initiating the mixed-meal ingestion and at 30, 60 and 120 minutes after the mixed meal ingestion.
measure: Continuous Glucose Monitoring (CGM) - Change in Average Daily 24-hour Glucose Concentration at Week 12
timeFrame: Baseline and 12 weeks
measure: Seven-Point Glucose Profile - Change in Average 24-h Glucose Concentrations
timeFrame: Baseline and 12 weeks
measure: Summary of the Product of Average Daily 24-h Glucose Ratio and Daily Insulin Use Ratio (Day 78 [Week 12]/Baseline)
timeFrame: Baseline and week 12
measure: Change in Hemoglobin A1c From Baseline at Week 13
timeFrame: Baseline and 13 weeks
measure: Percentage of Subjects With HbA1c Reduction of ≥ 0.4% at Week 13
timeFrame: Baseline and 13 weeks
measure: Change in C-peptide Adjusted AUC Following Mixed Meal Tolerance Test (MMTT)
timeFrame: Baseline and 13 weeks; AUC C-peptide timepoints: 10 minutes prior and just before (time 0) initiating the mixed-meal ingestion and at 30, 60 and 120 minutes after the mixed meal ingestion.
measure: Change in Baseline Difference in Glucagon Adjusted AUC Following Mixed Meal Tolerance Test (MMTT) - Part A Only
timeFrame: Baseline and 13 weeks; AUC glucagon timepoints: 10 minutes prior and just before (time ) initiating the mixed-meal ingestion and at 30, 60 and 120 minutes after the mixed meal ingestion.
measure: Proportion of Subjects With Positive Anti-REMD-477 Antibodies
timeFrame: Day 1 (pre-dose), Day 85 (Week 13) and Day 162 (Week 24)
measure: Summary of REMD-477 Plasma Concentrations
timeFrame: Baseline (Day 1 pre-dose) and Weeks 2, 5, 9, 13 and 16.
measure: Change in Hemoglobin A1c at Week 13 in Subjects With Baseline HbA1c ≥7.5%
timeFrame: Baseline and 13 weeks
measure: Proportion of Subjects With Targeted Hemoglobin A1C (HbA1c) of ≤ 7.0% at Week 13
timeFrame: Baseline and 13 weeks
measure: Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Target Blood Glucose Range (70-180 mg/dL) at Week 12
timeFrame: Baseline and 12 weeks
measure: Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hyperglycemia (Blood Glucose Range >180 mg/dL) at Week 12
timeFrame: Baseline and 12 weeks
measure: Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <70 mg/dL) at Week 12
timeFrame: Baseline and 12 weeks
measure: Continuous Glucose Monitoring (CGM) - Change in Percent Time Spent in Hypoglycemia (Blood Glucose Range <55 mg/dL) at Week 12
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
city: Escondido
country: United States
facility: AMCR Institute
state: California
city: Greenbrae
country: United States
facility: Marin Endocrine Care & Research
state: California
city: San Diego
country: United States
facility: Altman Clinical and Translational Research Institute
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research
state: California
city: Aurora
country: United States
facility: University of Colorado, Denver/Barbara Davis Center for Diabetes
state: Colorado
city: Atlanta
country: United States
facility: Atlanta Diabetes Assoicates
state: Georgia
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Austin
country: United States
facility: Texas Diabetes & Endocrinology
state: Texas
city: Dallas
country: United States
facility: Dallas Diabetes Research Center
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas
state: Texas
city: Renton
country: United States
facility: Rainer Clinical Research Center
state: Washington
Study officials:
References: