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

May 5, 2025 updated by: Alnylam Pharmaceuticals

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)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
      • Toronto, Canada
        • Clinical Trial Site
    • Ontario
      • Sarnia, Ontario, Canada
        • Clinical Trial Site
    • Quebec
      • Montréal, Quebec, Canada
        • Clinical Trial Site
      • Victoriaville, Quebec, Canada
        • Clinical Trial Site
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85020
        • Clinical Trial Site
    • California
      • Vista, California, United States, 92083
        • Clinical Trial Site
    • Florida
      • Lake Worth, Florida, United States, 33461
        • Clinical Trial Site
      • Orlando, Florida, United States, 32806
        • Clinical Trial Site
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Clinical Trial Site
    • New Jersey
      • Berlin, New Jersey, United States, 08009
        • Clinical Trial Site
    • North Carolina
      • Monroe, North Carolina, United States, 28110
        • Clinical Trial Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • Clinical Trial Site
    • Texas
      • Dallas, Texas, United States, 75234
        • Clinical Trial Site
      • Houston, Texas, United States, 77036
        • Clinical Trial Site
      • San Antonio, Texas, United States, 78229
        • Clinical Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Part A: Frequency of Adverse Events
Time Frame: Up to 9 Months
Up to 9 Months
Part B: Frequency of Adverse Events
Time Frame: Up to 12 Months
Up to 12 Months

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alnylam Pharmaceuticals

Investigators

  • Study Director: Medical Director, Alnylam Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 10, 2023

Primary Completion (Actual)

April 3, 2025

Study Completion (Actual)

April 3, 2025

Study Registration Dates

First Submitted

February 24, 2023

First Submitted That Met QC Criteria

March 7, 2023

First Posted (Actual)

March 9, 2023

Study Record Updates

Last Update Posted (Actual)

May 7, 2025

Last Update Submitted That Met QC Criteria

May 5, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALN-KHK-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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