ALN-KHK for Type 2 Diabetes

No longer recruiting at 21 trial locations

Overseen By Alnylam Clinical Trial Information Line

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Alnylam Pharmaceuticals

Disqualifiers: Type 1 diabetes, investigational agent, others

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called ALN-KHK for individuals with Type 2 Diabetes. The goal is to assess its safety and effectiveness by administering different doses compared to a placebo (a harmless pill with no active medicine). The trial consists of two parts: one examines a single dose, and the other examines multiple doses. Individuals with Type 2 Diabetes, a BMI between 30 and 39.9, and HbA1c levels between 7.5% and less than 10% might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that ALN-KHK is likely to be safe for humans?

Research has shown that ALN-KHK is likely safe. Studies found that all side effects were mild, not serious, and resolved on their own. This indicates that people generally tolerated the treatment well.

There's more good news. Individuals with certain genetic traits that naturally lower KHK activity, which ALN-KHK aims to replicate, remain healthy. This suggests the treatment's method is safe.

Overall, these early findings are encouraging for those considering participation in trials with ALN-KHK. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Type 2 Diabetes?

Researchers are excited about ALN-KHK for type 2 diabetes because it offers a novel approach to managing the condition. Unlike standard treatments like metformin or insulin, ALN-KHK targets a different pathway by employing RNA interference (RNAi) technology to potentially reduce the production of proteins that contribute to insulin resistance. This innovative mechanism could lead to better blood sugar control with fewer side effects. Additionally, the potential for both single and multiple dosing options provides flexibility and could improve patient adherence compared to daily medications.

What evidence suggests that ALN-KHK might be an effective treatment for Type 2 Diabetes?

Research has shown that ALN-KHK, a new therapy tested in this trial, could help treat type 2 diabetes. Early studies found that ALN-KHK treatment increased blood fructose levels and significantly lowered FGF21, a hormone involved in metabolism. These changes suggest that ALN-KHK might help control blood sugar levels and improve overall metabolic health. Initial results support further testing of ALN-KHK in patients, indicating its potential to effectively manage type 2 diabetes. Participants in this trial will receive either ALN-KHK or a placebo to evaluate its effectiveness and safety. ^{1 3 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Alnylam Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for overweight to obese healthy individuals and those with Type 2 Diabetes Mellitus (T2DM). Healthy participants need a BMI between 27-34.9, while T2DM patients require a BMI of 32-39.9, an HbA1c level of at least 7.5% but less than 10%, and stable thyroid function without recent changes.

Inclusion Criteria

Your body mass index (BMI) is between 27 and 34.9.

My thyroid condition has been stable with no changes for at least 4 months.

My BMI is between 32 and 39.9, I have type 2 diabetes, and my HbA1c is between 7.5% and 10%.

Exclusion Criteria

I have a history of either Type 1 or Type 2 diabetes.

You have a history of type 1 diabetes.

You have used an experimental drug in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive a single ascending dose of ALN-KHK or placebo

1 week

Treatment Part B

Participants receive multiple doses of ALN-KHK or placebo

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ALN-KHK

Trial Overview The study tests ALN-KHK against a placebo in two parts: one focusing on safety and how the body processes single doses in healthy volunteers, and another looking at multiple doses' safety, tolerability, and effectiveness in obese T2DM patients.

How Is the Trial Designed?

Group I: Part B: ALN-KHK Experimental Treatment 1 Intervention

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

Group II: Part A: ALN-KHK Experimental Treatment 1 Intervention

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

Group III: Part B: Placebo Placebo Group 1 Intervention

Participants will be administered a multiple doses of placebo.

Group IV: Part A: Placebo Placebo Group 1 Intervention

Participants will be administered a single dose of placebo.

Who Is Running the Clinical Trial?

Alnylam Pharmaceuticals

Lead Sponsor

Trials

81

Recruited

16,100+

Dr. Yvonne Greenstreet

Alnylam Pharmaceuticals

Chief Executive Officer since 2021

MD from the University of Leeds, MBA from INSEAD

Dr. Pushkal Garg

Alnylam Pharmaceuticals

Chief Medical Officer since 2016

MD from Columbia University

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05761301

NCT05761301 | A Phase 1/2 Study to Evaluate ALN-KHK ... Study Overview. To evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of ALN-KHK and to evaluate the ...

2. capella.alnylam.com capella.alnylam.com/wp-content/uploads/2024/06/ALN-KHK-Phase-1-2-ADA_POS_Final.pdf

ALN-KHK, an Investigational RNA Interference Therapeutic ... • Results of this first clinical study of ALN-KHK support its further evaluation in patients with type 2 diabetes and suggest the potential.

3. researchgate.net researchgate.net/publication/371747346_830-P_Preclinical_Development_of_ALN-KHK_an_Investigational_RNAi_Therapeutic_for_Type_2_Diabetes_Mellitus

830-P: Preclinical Development of ALN-KHK, an ... ALN-KHK treatment resulted in a dose-dependent increase in circulating fructose with a 4.6-fold increase and a 10.7-fold decrease in FGF21 (which is regulated ...

4. clinicaltrial.be clinicaltrial.be/en/details/260958?per_page=100&only_recruiting=0&only_eligible=0

A Phase 1/2 Study to Evaluate ALN-KHK in Overweight ... To evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of ALN-KHK and to evaluate the ...

5. dev-alnylam-sponsor-trials.xogene.com dev-alnylam-sponsor-trials.xogene.com/trials/034a05af3e844aba

Alnylam - ALN-KHK-001 To evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of ALN-KHK and to evaluate the safety, ...

6. diabetesjournals.org diabetesjournals.org/diabetes/article/72/Supplement_1/830-P/150522/830-P-Preclinical-Development-of-ALN-KHK-an

830-P: Preclinical Development of ALN-KHK, an ... ALN-KHK treatment resulted in a dose-dependent increase in circulating fructose with a 4.6-fold increase and a 10.7-fold decrease in FGF21 ( ...

7. capella.alnylam.com capella.alnylam.com/wp-content/uploads/2023/06/230608_KHK_ADA_Poster-1.pdf

ALN-KHK ADA 2023 - Capella Individuals with homozygous mutations in KHK are healthy supporting the safety of knocking down KHK. Conclusions. • ALN-KHK demonstrated ...

8. diabetesjournals.org diabetesjournals.org/diabetes/article/73/Supplement_1/859-P/156520/859-P-ALN-KHK-an-Investigational-RNA-Interference

859-P: ALN-KHK, an Investigational RNA Interference ... By data cutoff, all adverse events were mild, non-serious, and resolved. Increasing doses of ALN-KHK were generally associated with dose- and ...