A Phase 1/2 Study to Evaluate ALN-KHK in Overweight to Obese Healthy Volunteers and Obese Patients With T2DM

Type 2 Diabetes Mellitus (T2DM) Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05761301
• Other study ID #: ALN-KHK-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 10, 2023
• Est. completion date: July 2025

Study information

• Verified date: May 2024
• Source: Alnylam Pharmaceuticals
• Contact: Alnylam Clinical Trial Information Line
• Phone: 1-877-ALNYLAM
• Email: clinicaltrials[@]alnylam.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: July 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 (=8 years)

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Overweight
• Type 2 Diabetes Mellitus (T2DM)

Intervention

Drug:
• ALN-KHK
ALN-KHK will be administered by subcutaneous (SC) injection.
• Placebo
Placebo will be administered by subcutaneous (SC) injection.

Locations

Country	Name	City	State
Canada	Clinical Trial Site	Montréal	Quebec
Canada	Clinical Trial Site	Sarnia	Ontario
Canada	Clinical Trial Site	Victoriaville	Quebec
United States	Clinical Trial Site	Lake Worth	Florida
United States	Clinical Trial Site	Oklahoma City	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Frequency of Adverse Events		Up to 9 Months
Primary	Part B: Frequency of Adverse Events		Up to 12 Months
Secondary	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
Secondary	Part A: Maximum Observed Plasma Concentration (Cmax) of ALN-KHK and Potential Major Metabolite(s)		Up to 2 Days following dosing on Day 1
Secondary	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
Secondary	Part A: Fraction of ALN-KHK Excreted in the Urine (fe) and Potential Major Metabolite(s)		Postdose on Day 1
Secondary	Part A: Percent Change from Baseline in Circulating Fructose in Response to a Fructose Tolerance Test		Baseline up to Month 6
Secondary	Part A: Percent Change from Baseline in Urinary Fructose in Response to a Fructose Tolerance Test		Baseline up to Month 6
Secondary	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
Secondary	Part B: Absolute Change from Baseline in Hemoglobin A1C (HbA1c) at 6 Months		Baseline and Month 6
Secondary	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
Secondary	Part B: Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)		Month 4
Secondary	Parts A and B: Glucose and Insulin AUC in response to Tolerance Test		Part A: Screening up to Month 3; Part B: Month 4
Secondary	Part B: Plasma Concentrations of ALN-KHK and Potential Major Metabolite(s)		Day 1 and Month 3