Clinical trial NCT05761301: A Phase 1/2 Study to Evaluate ALN-KHK in Overweight to Obese Healthy Volunteers and Obese Patients With T2DM
Official title: A Phase 1/2, Randomized, Double-blind, Placebo-controlled, 2-Part Study of the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Single Dose ALN-KHK in Overweight to Obese Adult Healthy Volunteers and Multiple Dose ALN-KHK in Obese Patients With Type 2 Diabetes Mellitus (T2DM)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Type 2 Diabetes Mellitus (T2DM)
Keywords: Overweight
Obese
Fructose
siRNA
HbA1C
Insulin
Glucose
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-03-09
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The single ascending dose part of this study (Part A) will have a sequential interventional study model. The multi-dose part of this study (Part B) will have a parallel interventional study model and will begin after the completion of Part A.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Part A: Frequency of Adverse Events
timeFrame: Up to 9 Months
measure: Part B: Frequency of Adverse Events
timeFrame: Up to 12 Months
Secondary outcomes:
measure: Part A: Area Under the Concentration-time Curve (AUC) of ALN-KHK and Potential Major Metabolite(s)
timeFrame: Up to 2 Days following dosing on Day 1
measure: Part A: Maximum Observed Plasma Concentration (Cmax) of ALN-KHK and Potential Major Metabolite(s)
timeFrame: Up to 2 Days following dosing on Day 1
measure: Part A: Time to Maximum Observed Plasma Concentration (Tmax) of ALN-KHK and Potential Major Metabolite(s)
timeFrame: Up to 2 Days following dosing on Day 1
measure: Part A: Fraction of ALN-KHK Excreted in the Urine (fe) and Potential Major Metabolite(s)
timeFrame: Postdose on Day 1
measure: Part A: Percent Change from Baseline in Circulating Fructose in Response to a Fructose Tolerance Test
timeFrame: Baseline up to Month 6
measure: Part A: Percent Change from Baseline in Urinary Fructose in Response to a Fructose Tolerance Test
timeFrame: Baseline up to Month 6
measure: Part A: Percent Change from Baseline in Circulating Fibroblast Growth Factor 21 (FGF21) in Response to a Fructose Tolerance Test
timeFrame: Baseline up to Month 6
measure: Part B: Absolute Change from Baseline in Hemoglobin A1C (HbA1c) at 6 Months
timeFrame: Baseline and Month 6
measure: Parts A and B: Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in Response to a Glucose Tolerance Test
timeFrame: Part A: Screening up to Month 3; Part B: Month 4
measure: Part B: Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
timeFrame: Month 4
measure: Parts A and B: Glucose and Insulin AUC in response to Tolerance Test
timeFrame: Part A: Screening up to Month 3; Part B: Month 4
measure: Part B: Plasma Concentrations of ALN-KHK and Potential Major Metabolite(s)
timeFrame: Day 1 and Month 3
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Clinical Trial Site
state: Arizona
city: Vista
country: United States
facility: Clinical Trial Site
state: California
city: Lake Worth
country: United States
facility: Clinical Trial Site
state: Florida
city: Orlando
country: United States
facility: Clinical Trial Site
state: Florida
city: Atlanta
country: United States
facility: Clinical Trial Site
state: Georgia
city: Berlin
country: United States
facility: Clinical Trial Site
state: New Jersey
city: Monroe
country: United States
facility: Clinical Trial Site
state: North Carolina
city: Oklahoma City
country: United States
facility: Clinical Trial Site
state: Oklahoma
city: Dallas
country: United States
facility: Clinical Trial Site
state: Texas
city: Houston
country: United States
facility: Clinical Trial Site
state: Texas
city: San Antonio
country: United States
facility: Clinical Trial Site
state: Texas
city: Sarnia
country: Canada
facility: Clinical Trial Site
state: Ontario
city: Montréal
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Victoriaville
country: Canada
facility: Clinical Trial Site
state: Quebec
city: Toronto
country: Canada
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References: