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

NCT05761301 | Terminated Phase 1 FDA Drug

• 1 other identifier: ALN-KHK-001
• Study Type: interventional
• Target: 49
• Locations: 2 countries
• Sites: 15

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.

Conditions

Type 2 Diabetes Mellitus (T2DM)

Keywords

Overweight; Obese; Fructose; siRNA; HbA1C; Insulin; Glucose

Outcome Measures

Primary Outcomes (2)

• Part A: Frequency of Adverse Events

  Up to 9 Months

• Part B: Frequency of Adverse Events

  Up to 12 Months

Secondary Outcomes (12)

• 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)

  Postdose on Day 1

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

  Baseline up to Month 6

Study Arms (4)

Part A: ALN-KHK

EXPERIMENTAL

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

Drug: ALN-KHK

Part A: Placebo

PLACEBO COMPARATOR

Participants will be administered a single dose of placebo.

Drug: Placebo

Part B: ALN-KHK

EXPERIMENTAL

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

Drug: ALN-KHK

Part B: Placebo

PLACEBO COMPARATOR

Participants will be administered a multiple doses of placebo.

Drug: Placebo

Interventions

ALN-KHK DRUG

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

Part A: ALN-KHK; Part B: ALN-KHK

Placebo DRUG

Placebo will be administered by subcutaneous (SC) injection.

Part A: Placebo; Part B: Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alnylam Pharmaceuticals: lead

Study Sites (15)

Clinical Trial Site

Phoenix, Arizona, 85020, United States

Location

Clinical Trial Site

Vista, California, 92083, United States

Location

Clinical Trial Site

Lake Worth, Florida, 33461, United States

Location

Clinical Trial Site

Orlando, Florida, 32806, United States

Location

Clinical Trial Site

Atlanta, Georgia, 30342, United States

Location

Clinical Trial Site

Berlin, New Jersey, 08009, United States

Location

Clinical Trial Site

Monroe, North Carolina, 28110, United States

Location

Clinical Trial Site

Oklahoma City, Oklahoma, 73112, United States

Location

Clinical Trial Site

Dallas, Texas, 75234, United States

Location

Clinical Trial Site

Houston, Texas, 77036, United States

Location

Clinical Trial Site

San Antonio, Texas, 78229, United States

Location

Clinical Trial Site

Sarnia, Ontario, Canada

Location

Clinical Trial Site

Montreal, Quebec, Canada

Location

Clinical Trial Site

Victoriaville, Quebec, Canada

Location

Clinical Trial Site

Toronto, Canada

Location

Related Publications (1)

• 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. 2025 Dec 12. doi: 10.1007/s40262-025-01606-0. Online ahead of print.

  PMID: 41388232 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Overweight; Obesity; Insulin Resistance

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism

Study Officials

• Medical Director

  Alnylam Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 24, 2023
• First Posted: March 9, 2023
• Study Start: March 10, 2023
• Primary Completion: April 3, 2025
• Study Completion: April 3, 2025
• Last Updated: May 7, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (11); CA (4)