A Phase 1/2 Study to Evaluate ALN-KHK in Overweight to Obese Healthy Volunteers and Obese Patients With T2DM
- Registration Number
- NCT05761301
- Lead Sponsor
- Alnylam Pharmaceuticals
- Brief Summary
To evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of ALN-KHK and to evaluate the safety, tolerability, efficacy, PK and PD of multiple doses of KHK.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 49
Inclusion Criteria
- Stable euthyroid status (no known changes in thyroid function; stable hormone replacement for at least 4 months) at screening
- Part A: body mass index (BMI) ≥27 kg/m^2 and ≤34.9 kg/m^2
- Part B: BMI ≥30 kg/m^2 to ≤39.9 kg/m^2, confirmed diagnosis of T2DM, and an HbA1c ≥7.5% to <10%
- Part B: Confirmed T2DM diagnosis
Exclusion Criteria
- Parts A and B: has received an investigational agent within the last 30 days
- Part A: History of Type 1 or Type 2 diabetes
- Part B: History of Type 1 diabetes
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: Placebo Placebo Participants will be administered a single dose of placebo. Part B: Placebo Placebo Participants will be administered a multiple doses of placebo. Part A: ALN-KHK ALN-KHK Participants will be administered a single dose of ALN-KHK. Part B: ALN-KHK ALN-KHK Participants will be administered a multiple doses of ALN-KHK.
- Primary Outcome Measures
Name Time Method Part A: Frequency of Adverse Events Up to 9 Months Part B: Frequency of Adverse Events Up to 12 Months
- Secondary Outcome Measures
Name Time Method Part B: Absolute Change from Baseline in Hemoglobin A1C (HbA1c) at 6 Months Baseline and Month 6 Part A: Fraction of ALN-KHK Excreted in the Urine (fe) and Potential Major Metabolite(s) Postdose on Day 1 Part B: Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Month 4 Part A: Area Under the Concentration-time Curve (AUC) of ALN-KHK and Potential Major Metabolite(s) Up to 2 Days following dosing on Day 1 Part A: Maximum Observed Plasma Concentration (Cmax) of ALN-KHK and Potential Major Metabolite(s) Up to 2 Days following dosing on Day 1 Part A: Time to Maximum Observed Plasma Concentration (Tmax) of ALN-KHK and Potential Major Metabolite(s) Up to 2 Days following dosing on Day 1 Part A: Percent Change from Baseline in Urinary Fructose in Response to a Fructose Tolerance Test Baseline up to Month 6 Part A: Percent Change from Baseline in Circulating Fibroblast Growth Factor 21 (FGF21) in Response to a Fructose Tolerance Test Baseline up to Month 6 Part B: Plasma Concentrations of ALN-KHK and Potential Major Metabolite(s) Day 1 and Month 3 Part A: Percent Change from Baseline in Circulating Fructose in Response to a Fructose Tolerance Test Baseline up to Month 6 Parts A and B: Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in Response to a Glucose Tolerance Test Part A: Screening up to Month 3; Part B: Month 4 Parts A and B: Glucose and Insulin AUC in response to Tolerance Test Part A: Screening up to Month 3; Part B: Month 4
Trial Locations
- Locations (1)
Clinical Trial Site
🇨🇦Toronto, Canada