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

Primary Purpose

Type 2 Diabetes Mellitus (T2DM)

Status

Recruiting

Phase

Phase 1

Locations

Canada

Study Type

Interventional

Intervention

ALN-KHK

Placebo

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus (T2DM) focused on measuring Overweight, Obese, Fructose, siRNA, HbA1C, Insulin, Glucose

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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) 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

Sites / Locations

Clinical Trial SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

Part A: ALN-KHK

Part A: Placebo

Part B: ALN-KHK

Part B: Placebo

Arm Description

Participants will be administered a single dose of ALN-KHK.

Participants will be administered a single dose of placebo.

Participants will be administered a multiple doses of ALN-KHK.

Participants will be administered a multiple doses of placebo.

Outcomes

Primary Outcome Measures

Part A: Frequency of Adverse Events

Part B: Frequency of Adverse Events

Secondary Outcome Measures

Part A: Area Under the Concentration-time Curve (AUC) of ALN-KHK and Potential Major Metabolite(s)

Part A: Maximum Observed Plasma Concentration (Cmax) of ALN-KHK and Potential Major Metabolite(s)

Part A: Time to Maximum Observed Plasma Concentration (Tmax) of ALN-KHK and Potential Major Metabolite(s)

Part A: Fraction of ALN-KHK Excreted in the Urine (fe) and Potential Major Metabolite(s)

Part A: Percent Change from Baseline in Circulating Fructose in Response to a Fructose Tolerance Test

Part A: Percent Change from Baseline in Urinary Fructose in Response to a Fructose Tolerance Test

Part A: Percent Change from Baseline in Circulating Fibroblast Growth Factor 21 (FGF21) in Response to a Fructose Tolerance Test

Part B: Absolute Change from Baseline in Hemoglobin A1C (HbA1c) at 6 Months

Part B: Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in Response to a Glucose Tolerance Test

Part B: Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)

Part B: Glucose and Insulin AUC in response to Tolerance Test

Part B: Plasma Concentrations of ALN-KHK and Potential Major Metabolite(s)

Full Information

NCT ID

NCT05761301

First Posted

February 24, 2023

Last Updated

October 16, 2023

Sponsor

Alnylam Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT05761301

Brief Title

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

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

March 10, 2023 (Actual)

Primary Completion Date

June 2024 (Anticipated)

Study Completion Date

July 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Alnylam Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes Mellitus (T2DM)

Keywords

Overweight, Obese, Fructose, siRNA, HbA1C, Insulin, Glucose

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

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.

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Part A: ALN-KHK

Arm Type

Experimental

Arm Description

Participants will be administered a single dose of ALN-KHK.

Arm Title

Part A: Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will be administered a single dose of placebo.

Arm Title

Part B: ALN-KHK

Arm Type

Experimental

Arm Description

Participants will be administered a multiple doses of ALN-KHK.

Arm Title

Part B: Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will be administered a multiple doses of placebo.

Intervention Type

Drug

Intervention Name(s)

ALN-KHK

Intervention Description

ALN-KHK will be administered by subcutaneous (SC) injection.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo will be administered by subcutaneous (SC) injection.

Primary Outcome Measure Information:

Title

Part A: Frequency of Adverse Events

Time Frame

Up to 9 Months

Title

Part B: Frequency of Adverse Events

Time Frame

Up to 12 Months

Secondary Outcome Measure Information:

Title

Part A: Area Under the Concentration-time Curve (AUC) of ALN-KHK and Potential Major Metabolite(s)

Time Frame

Up to 2 Days following dosing on Day 1

Title

Part A: Maximum Observed Plasma Concentration (Cmax) of ALN-KHK and Potential Major Metabolite(s)

Time Frame

Up to 2 Days following dosing on Day 1

Title

Part A: Time to Maximum Observed Plasma Concentration (Tmax) of ALN-KHK and Potential Major Metabolite(s)

Time Frame

Up to 2 Days following dosing on Day 1

Title

Part A: Fraction of ALN-KHK Excreted in the Urine (fe) and Potential Major Metabolite(s)

Time Frame

Up to 2 Days following dosing on Day 1

Title

Part A: Percent Change from Baseline in Circulating Fructose in Response to a Fructose Tolerance Test

Time Frame

Baseline up to Month 6

Title

Part A: Percent Change from Baseline in Urinary Fructose in Response to a Fructose Tolerance Test

Time Frame

Baseline up to Month 6

Title

Part A: Percent Change from Baseline in Circulating Fibroblast Growth Factor 21 (FGF21) in Response to a Fructose Tolerance Test

Time Frame

Baseline up to Month 6

Title

Part B: Absolute Change from Baseline in Hemoglobin A1C (HbA1c) at 6 Months

Time Frame

Baseline and Month 6

Title

Part B: Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in Response to a Glucose Tolerance Test

Time Frame

Month 4

Title

Part B: Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)

Time Frame

Month 4

Title

Part B: Glucose and Insulin AUC in response to Tolerance Test

Time Frame

Month 4

Title

Part B: Plasma Concentrations of ALN-KHK and Potential Major Metabolite(s)

Time Frame

Day 1 and Month 3

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Alnylam Clinical Trial Information Line

Phone

1-877-ALNYLAM

clinicaltrials@alnylam.com

First Name & Middle Initial & Last Name or Official Title & Degree

Alnylam Clinical Trial Information Line

Phone

1-877-256-9526

clinicaltrials@alnylam.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Alnylam Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Clinical Trial Site

City

Montréal

State/Province

Quebec

Country

Canada

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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