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Type 2 Diabetes Mellitus (T2DM)Phase 1/2NCT05761301

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

A Phase 1/2 study testing ALN-KHK in people with Type 2 Diabetes Mellitus (T2DM), run by Alnylam Pharmaceuticals at 15 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Type 2 Diabetes Mellitus (T2DM)
What is being tested?
ALN-KHK
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
49 participants
Where
15 sitesin 2 countries
Study dates
10 Mar 2023to 3 Apr 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

15 sites in 2 countries.

15 sites in 2 countries

United States11 sites

  • Clinical Trial Site

    Atlanta, Georgia, 30342

  • Clinical Trial Site

    Berlin, New Jersey, 08009

  • Clinical Trial Site

    Dallas, Texas, 75234

  • Clinical Trial Site

    Houston, Texas, 77036

  • Clinical Trial Site

    Lake Worth, Florida, 33461

  • Clinical Trial Site

    Monroe, North Carolina, 28110

  • Clinical Trial Site

    Oklahoma City, Oklahoma, 73112

  • Clinical Trial Site

    Orlando, Florida, 32806

  • Clinical Trial Site

    Phoenix, Arizona, 85020

  • Clinical Trial Site

    San Antonio, Texas, 78229

  • Clinical Trial Site

    Vista, California, 92083

Other trials in United States

Canada4 sites

  • Clinical Trial Site

    Montreal, Quebec

  • Clinical Trial Site

    Sarnia, Ontario

  • Clinical Trial Site

    Toronto

  • Clinical Trial Site

    Victoriaville, Quebec

Other trials in Canada

About this study

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)

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.

Being tested
ALN-KHK, Placebo
Keywords
Overweight, Obese, Fructose, siRNA, HbA1C, Insulin, Glucose
Medical subject headings
Diabetes Mellitus, Type 2, Overweight, Obesity, Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ALN-KHKDrug

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

  • PlaceboDrug

    Placebo will be administered by subcutaneous (SC) injection.

Study groups in NCT05761301
Study groupRoleWhat they receive
Part A: ALN-KHKExperimentalParticipants will be administered a single dose of ALN-KHK.
Receives: Drug: ALN-KHK
Part A: PlaceboPlacebo comparatorParticipants will be administered a single dose of placebo.
Receives: Drug: Placebo
Part B: ALN-KHKExperimentalParticipants will be administered a multiple doses of ALN-KHK.
Receives: Drug: ALN-KHK
Part B: PlaceboPlacebo comparatorParticipants will be administered a multiple doses of placebo.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A: Frequency of Adverse Events

    Measured: Up to 9 Months

  2. Part B: Frequency of Adverse Events

    Measured: Up to 12 Months

Secondary outcomes (12)

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

    Measured: Up to 2 Days following dosing on Day 1

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

    Measured: Up to 2 Days following dosing on Day 1

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

    Measured: Up to 2 Days following dosing on Day 1

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

    Measured: Postdose on Day 1

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

    Measured: Baseline up to Month 6

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

    Measured: Baseline up to Month 6

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

    Measured: Baseline up to Month 6

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

    Measured: Baseline and Month 6

  9. Parts A and B: Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in Response to a Glucose Tolerance Test

    Measured: Part A: Screening up to Month 3; Part B: Month 4

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

    Measured: Month 4

  11. Parts A and B: Glucose and Insulin AUC in response to Tolerance Test

    Measured: Part A: Screening up to Month 3; Part B: Month 4

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

    Measured: Day 1 and Month 3

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Mar 2023
  2. Study start10 Mar 2023
  3. Primary completion3 Apr 2025
  4. Study completion3 Apr 2025

Why it stopped: Business reasons (not safety related)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
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
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05761301
Sponsor's protocol ID
ALN-KHK-001
Status last verified
May 2025
First submitted
24 Feb 2023
Last updated
7 May 2025
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Badri P, Kolachana K, Duong A, Lasko M, Nandi T, Mehrotra N, Robbie GJ. Platform Assessment of Concentration-QTc Relationship Across GalNAc-siRNA Molecules. Clin Pharmacokinet. 2026 Feb;65(2):293-311. doi: 10.1007/s40262-025-01606-0. Epub 2025 Dec 12.

    PubMed 41388232

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ALN-KHK in people with Type 2 Diabetes Mellitus (T2DM), run by Alnylam Pharmaceuticals at 15 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Business reasons (not safety related)). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Frequency of Adverse Events (time frame: Up to 9 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05761301, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2025.

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