Overweight or Obese Adults, Overweight or Obese, Type 2 Diabetes
Conditions
Keywords
Overweight, Obese, Obesity, Type 2 Diabetes, Weight loss
Brief summary
A Study of ALV-100 to Assess Safety, Tolerability, and PK/PD in Overweight/Obese Participants with or without Type 2 Diabetes
Interventions
DRUGALV-100
Participants will receive multiple ascending doses of ALV-100.
DRUGPlacebo
Participants will receive placebo matching ALV-100, volume-matched to active dose.
Sponsors
Alveus Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sponsor
Intervention model description
In Part A, four treatment cohorts of participants with overweight or obesity will be administered varying dose escalation regimens of ALV-100. Each cohort will explore the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple doses of ALV-100. Each cohort will be comprised of 40 participants with 32 participants receiving active treatment and 8 participants receiving placebo in a 4:1 ratio. In Part B, a single cohort of participants with overweight or obesity, and T2D will be enrolled. This cohort will explore the safety (including glycemic safety), tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of ALV-100. Fifteen (15) participants will receive active treatment, and 5 participants will receive placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
For Part A and B * Adult male and female participants, aged 18 to 65 years, inclusive, at the time of signing the informed consent form * Body mass index between 27.0 to 39.9 kg/m2 at Screening, both inclusive; overweight should be due to excess adipose tissue, as judged by the Investigator. * Have a stable body weight (\< 5.0 kg/11 lbs self-reported change) within 90 days prior to Screening * Females must be surgically sterile (by means of bilateral salpingectomy, hysterectomy or bilateral oophorectomy) or be post-menopausal (defined as spontaneous cessation of menses for at least 1 year prior to Screening). Females who are post-menopausal and \< 55 years must have a follicle-stimulating hormone level \> 40 IU/L at Screening. * Males with female partners of child-bearing potential must be willing to practice abstinence or must agree to use condom as contraception throughout the duration of the study. This criterion may be waived for male participants who have had a documented successful vasectomy \> 6 months before signing the ICF. For Part B only * Diagnosis of Type 2 Diabetes for at least 180 days prior to Screening. * Glycemic control managed by diet and exercise alone or by stable treatment with metformin and/or sodium-glucose cotransporter 2 inhibitors (SGLT-2i), with no dose changes within 3 months prior to Screening. * Hemoglobin A1c (HbA1c) between 6.5 % and 9.0% (equivalent to 48-75 mmol/mol), both inclusive, at Screening.
Exclusion criteria
For Part A and B * History or presence of any clinically relevant respiratory, metabolic (including dyslipidemia, however screening total cholesterol below or equal to 302 mg/dL (7.8 mmol/L) and/or screening triglyceride below or equal to 500 mg/dL (5.65 mmol/L) is accepted), renal, hepatic, gastrointestinal, endocrinological conditions (except conditions associated with type 2 diabetes in Part B) at the discretion of the Investigator. * Participants with a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 or a personal history of nonfamilial medullary thyroid carcinoma. * Current or history of chronic or acute pancreatitis. * Obesity caused by known endocrinologic disorders (e.g., Cushing syndrome) or monogenetic or syndromic forms of obesity (for example, Melanocortin 4 Receptor deficiency or Prader Willi Syndrome). * History of major depressive disorder or other severe psychiatric disorder (for example, schizophrenia, bipolar disorder, or anxiety disorder). * Lifetime history of a suicide attempt or of any suicidal behavior by endorsement of (answered yes to) any of the items in the suicidal behavior section on the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening. * Systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg at Screening. * History of or current cardiovascular disease, including but not limited to stable and unstable angina, myocardial infarction, congestive heart failure, transient ischemic attack, stroke, clinically significant arrhythmias and conduction disorders or venous thromboembolism. Part A only • History or clinical evidence of Type 1 or Type 2 diabetes mellitus, including HbA1c ≥ 6.5% and/or a fasting plasma glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L) at Screening (female participants with a history of gestational diabetes are allowed). Part B only * Fasting plasma glucose (FPG) \> 270 mg/dL (15.0 mmol/L) at Screening. * Proliferative retinopathy or maculopathy as judged by the investigator based on a recent (within1.5 years from Screening) ophthalmologic examination. * Severe neuropathy as judged by the investigator. * Advanced nephropathy (defined as albuminuria ≥ 300 mg/g). * History of severe hypoglycemia or hypoglycemic unawareness as judged by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability | From First Dose to Week 52 | Incidence of treatment emergent adverse events (TEAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) of intact ALV-100 and total ALV-100 - Cmax, MD | From First Dose to Week 52 | Maximum observed serum concentration after multiple doses (MD) (Cmax, MD) |
| Pharmacokinetics (PK) of intact ALV-100 and total ALV-100 - AUC(0-τ), MD | From First Dose to Week 52 | Area under the serum concentration-time curve from time zero to τ, where τ is the dosing interval, (AUC(0-τ), MD) |
| Pharmacodynamic (PD) impact on body weight | Baseline, Week 32 and Week 52 | Change from baseline in body weight |
| Pharmacodynamic (PD) impact on body weight percentage | Baseline, Week 32 and Week 52 | Change from baseline in body weight percentage |
| Immunogenicity | From Baseline to Week 52 | Incidence of Anti-ALV-100 drug antibodies, including assessments of cross-reactivity and neutralizing antibodies. |
| Relationship between ALV-100 serum concentration and QTc interval changes (Part A Only) | From First Dose to Week 52 | Measurement of change in individual specific heart rate corrected QT interval (QTcI) and Fridericia heart rate corrected QT interval (QTcF) on 12-lead ECG. |
| Paracetamol (acetaminophen) absorption test (PAT) (Part A Only) | From First Dose to Week 52 | Measurement of acetaminophen PK parameters to evaluate the effect of ALV-100 on the gastric emptying rate. |
| Pharmacodynamic (PD) impact of ALV-100 on antidiabetic medication (Part B Only) | From Baseline to Week 32 | Change in use of concomitant glucose-lowering medication |
| Pharmacodynamic (PD) impact of ALV-100 on glycemic parameters (Part B Only) | Week 32 and Week 52 | Measuring the number of participants achieving target Hemoglobin A1c values |
| Hypoglycemic Safety (Part B Only) | From Baseline to Week 52 | Measured by the incidence of symptomatic hypoglycemia, documented symptomatic hypoglycemia and severe hypoglycemia |
Countries
United States
Contacts
CONTACTStudy Director
STUDY_DIRECTORKaren Tornøe, MD, PhD
Alveus Therapeutics
Outcome results
None listed