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

Sponsor

Alnylam Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05761301

Collaborator

(none)

160

Enrollment

Location

Arms

Anticipated Duration (Months)

5.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus (T2DM)	Drug: ALN-KHK Drug: Placebo	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

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.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.

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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)

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: ALN-KHK Participants will be administered a single dose of ALN-KHK.	Drug: ALN-KHK ALN-KHK will be administered by subcutaneous (SC) injection.
Placebo Comparator: Part A: Placebo Participants will be administered a single dose of placebo.	Drug: Placebo Placebo will be administered by subcutaneous (SC) injection.
Experimental: Part B: ALN-KHK Participants will be administered a multiple doses of ALN-KHK.	Drug: ALN-KHK ALN-KHK will be administered by subcutaneous (SC) injection.
Placebo Comparator: Part B: Placebo Participants will be administered a multiple doses of placebo.	Drug: Placebo Placebo will be administered by subcutaneous (SC) injection.

Outcome Measures

Primary Outcome Measures

Part A: Frequency of Adverse Events [Up to 9 Months]
Part B: Frequency of Adverse Events [Up to 12 Months]

Secondary Outcome Measures

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: Fraction of ALN-KHK Excreted in the Urine (fe) and Potential Major Metabolite(s) [Up to 2 Days following dosing on Day 1]
Part A: Percent Change from Baseline in Circulating Fructose in Response to a Fructose Tolerance Test [Baseline up to Month 6]
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: Absolute Change from Baseline in Hemoglobin A1C (HbA1c) at 6 Months [Baseline and Month 6]
Part B: Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in Response to a Glucose Tolerance Test [Month 4]
Part B: Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) [Month 4]
Part B: Glucose and Insulin AUC in response to Tolerance Test [Month 4]
Part B: Plasma Concentrations of ALN-KHK and Potential Major Metabolite(s) [Day 1 and Month 3]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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 ≥32 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)