ALN-PNP for Healthy Subjects

Recruiting at 5 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Regeneron Pharmaceuticals

Disqualifiers: Chronic liver disease, Type 1 diabetes, others

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 weeks

96 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, ALN-PNP, to determine its safety, tolerability, and effectiveness. Part A involves healthy individuals to assess potential side effects and the drug's behavior in the body. Part B targets those with non-alcoholic fatty liver disease (NAFLD) and a specific gene variant, focusing on the drug's impact on liver fat. Healthy adults who feel fit and have no major health issues qualify for Part A, while individuals with NAFLD and a liver fat content above 8.5% are suitable for Part B. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I need to stop my current medications to join the trial?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ALN-PNP is under study to assess its safety and tolerability. This new drug is undergoing its first tests in humans. Due to the early stage of testing, specific information about side effects remains limited.

As a Phase 1 trial, the primary goal is to evaluate the drug's safety. At this stage, researchers typically administer the drug to a small group of healthy individuals, closely monitoring any side effects. Although detailed safety information is not yet available, the trial is crucial to determine if the drug is safe for further testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

ALN-PNP is unique because it targets a specific pathway in the body that is not addressed by existing treatments. While most treatments for similar conditions rely on broad approaches, ALN-PNP uses a novel mechanism of action to precisely modify the underlying processes. Researchers are excited about the potential for ALN-PNP to offer a more targeted and effective option, potentially leading to improved outcomes with fewer side effects.

What evidence suggests that ALN-PNP might be an effective treatment for NAFLD?

Initial findings suggest that ALN-PNP might help reduce liver fat, a major issue in nonalcoholic fatty liver disease (NAFLD). ALN-PNP, an experimental drug, is being tested in humans for the first time. Researchers believe it targets a specific gene linked to liver fat buildup. Although human data is not yet available, the drug is designed to address the root cause of NAFLD. This trial will test various doses of ALN-PNP to determine if it can safely and effectively lower liver fat in people with this condition, with some participants receiving a placebo for comparison. ^{1 2 6 7 8}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for healthy adults, including specific criteria for Japanese participants such as being born in Japan with Japanese parents and grandparents, living a Japanese lifestyle, and not having lived outside of Japan for more than 10 years. Participants must have a BMI between 18-32 and be in good health based on lab tests. Smokers or recent smokers, those with significant diseases or abnormal lab results are excluded.

Inclusion Criteria

For Japanese cohorts ONLY; the Japanese participant must:

Be Japanese, born in Japan, and have both biologic parents and 4 biologic grandparents who are ethnically Japanese and born in Japan

Have maintained a Japanese lifestyle, with no significant change since leaving Japan, including having access to Japanese food and adhering to a Japanese diet

Exclusion Criteria

History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, neurological, or dermatologic disease, as assessed by the investigator, that may confound the results of the study or poses an additional risk to the participant by study participation

Presents any concern to the study investigator that might confound the results of the study or poses an additional risk to the participant by their participation in the study

Hospitalized for any reason within 30 days of the screening visit

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of ALN-PNP or placebo to assess safety, tolerability, and pharmacokinetics

Up to 36 weeks

Multiple visits for blood sampling and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 36 weeks

Optional Extension

Optional cohort for additional dose characterization of ALN-PNP

What Are the Treatments Tested in This Trial?

Interventions

• ALN-PNP
• Placebo

Trial Overview The study is testing the safety and how well people tolerate ALN-PNP when given once to healthy adults compared to a placebo. It will also look at how the body processes ALN-PNP, its effects on immune response, and any changes it might cause in blood lipid levels.

How Is the Trial Designed?

Group I: Part B: ALN-PNP Dose 5 Experimental Treatment 1 Intervention

Up to 32 Participants Randomized 1:1:1:1 resulting in 8 participants per arm

Group II: Part B: ALN-PNP Dose 4 Experimental Treatment 1 Intervention

Up to 32 Participants Randomized 1:1:1:1 resulting in 8 participants per arm

Group III: Part B: ALN-PNP Dose 3 Experimental Treatment 1 Intervention

Up to 32 Participants Randomized 1:1:1:1 resulting in 8 participants per arm

Group IV: Part A: Optional ALN-PNP Dose 5 or PB Experimental Treatment 2 Interventions

8 Participants, Randomized 6:2 This is an optional cohort, if there is a need for additional dose characterization of ALN-PNP.

Group V: Part A: JPN ALN-PNP Dose 5 or PB Experimental Treatment 2 Interventions

8 Japanese Participants only, Randomized 6:2

Group VI: Part A: JPN ALN-PNP Dose 4 or PB Experimental Treatment 2 Interventions

8 Japanese Participants only, Randomized 6:2

Group VII: Part A: ALN-PNP Dose 5 or PB Experimental Treatment 2 Interventions

8 Participants, Randomized 6:2

Group VIII: Part A: ALN-PNP Dose 4 or PB Experimental Treatment 2 Interventions

8 Participants, Randomized 6:2

Group IX: Part A: ALN-PNP Dose 3 or PB Experimental Treatment 2 Interventions

8 Participants, Randomized 6:2

Group X: Part A: ALN-PNP Dose 2 or PB Experimental Treatment 2 Interventions

8 Participants, Randomized 6:2

Group XI: Part A: ALN-PNP Dose 1 or PB Experimental Treatment 2 Interventions

8 Participants, Randomized 6:2

Group XII: Part B: Placebo Placebo Group 1 Intervention

Up to 32 Participants Randomized 1:1:1:1 resulting in 8 participants per arm

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Published Research Related to This Trial

In a review of 200 randomized drug trials published in 2013, only 1 trial (0.5%) used an active placebo, indicating that these control groups are rarely employed in clinical research.

Active placebos are more commonly found in trials involving drugs with noticeable side effects, as they help reduce the risk of unblinding, although they also carry the risk of causing unintended therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration: a methodological overview. Jensen, JS., Bielefeldt, AØ., Hróbjartsson, A.[2018]

The C1-C2 self-sustained natural apophyseal glide (SNAG) technique significantly improved the range of motion in the cervical spine by 15 degrees in participants with cervicogenic headaches, compared to only 5 degrees in the placebo group, indicating its effectiveness in addressing C1-C2 dysfunction.

Participants using the C1-C2 self-SNAG reported a substantial reduction in headache symptoms, with scores decreasing by 54% over 12 months, demonstrating its long-term efficacy in managing cervicogenic headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a C1-C2 self-sustained natural apophyseal glide (SNAG) in the management of cervicogenic headache. Hall, T., Chan, HT., Christensen, L., et al.[2022]

In a study involving 100 patients undergoing lumbar spine fusion surgeries, batroxobin and its combination with tranexamic acid significantly reduced both intraoperative and postoperative blood loss compared to a placebo.

The mean intraoperative blood loss was lowest in the batroxobin group (268.32 mL) and the combination group (256.96 mL), indicating their effectiveness, while no significant differences were found in blood transfusion needs or complications like deep vein thrombosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Batroxobin, Tranexamic Acid and a Combination in Reduction of Blood Loss in Lumbar Spinal Fusion Surgery. Nagabhushan, RM., Shetty, AP., Dumpa, SR., et al.[2021]

As effective therapies become more available, conducting placebo-controlled trials for serious illnesses may raise ethical concerns, making it challenging to deny patients effective treatments.

The article proposes a new method for analyzing data from active-controlled trials by leveraging existing knowledge from previous placebo-controlled trials, which can help determine the likelihood of significant differences between active treatments and placebos, thus improving the interpretation of trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Another view of active-controlled trials. Gould, AL.[2019]

In a study involving 10 volunteers with spinal cord injury, abdominal neuromuscular electrical stimulation (NMES) improved colonic transit in most segments but negatively impacted lung capacity, specifically forced vital capacity (FVC).

Participants in the NMES group reported higher satisfaction regarding the aesthetic effects on their abdominal wall compared to the placebo group, suggesting potential cosmetic benefits alongside functional improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromuscular electrical stimulation of completely paralyzed abdominal muscles in spinal cord-injured patients: a pilot study. Hascakova-Bartova, R., Dinant, JF., Parent, A., et al.[2011]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/nct05648214

A Trial to Learn if ALN-PNP is Safe and Well Tolerated in ... This study is researching an experimental drug called ALN-PNP (called "study drug"). This is a first in human study. The study drug is not approved by any ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05648214/a-trial-to-learn-if-aln-pnp-is-safe-and-well-tolerated-in-healthy-adults-and-adult-participants-with-non-alcoholic-fatty-liver-disease-nafld

A Trial to Learn if ALN-PNP is Safe and Well Tolerated in ... A Trial to Learn if ALN-PNP is Safe and Well Tolerated in Healthy Adults and Adult Participants With Non-Alcoholic Fatty Liver Disease (NAFLD).

3. clinicaltrial.be clinicaltrial.be/en/details/190556?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

A Trial to Learn if ALN-PNP is Safe and Well Tolerated in... This study is researching an experimental drug called ALN-PNP (called "study drug"). This is a first in human study. The study drug is not ...

4. withpower.com withpower.com/trial/phase-1-healthy-subjects-hs-11-2022-9cb63

ALN-PNP for Healthy Subjects The goal is to see if the drug is safe, tolerable, and effective in reducing liver fat. Researchers are also studying how the body processes the drug. Show more.

5. clinicaltrials.regeneron.com clinicaltrials.regeneron.com/clinical-trials/a0Mdy0000001BPfEAM/nct06024408

A Trial to Learn if Receiving ALN-PNP siRNA is Safe and Well ... This study is researching an experimental drug called ALN-PNP. This study is focused on participants who are known to have nonalcoholic fatty liver disease ...

6. clinicalresearch.com clinicalresearch.com/en/find-trials/Study/NCT05648214

NCT05648214 A trial to learn if ALN-PNP is safe and well tolerated in healthy adults and adult participants with non-alcoholic fatty liver disease (NAFLD).

7. ctv.veeva.com ctv.veeva.com/study/a-trial-to-learn-if-aln-pnp-is-safe-and-well-tolerated-in-adult-healthy-participants

A Trial to Learn if ALN-PNP is Safe and Well Tolerated in ... A Trial to Learn if ALN-PNP is Safe and Well Tolerated in Healthy Adults and Adult Participants With Non-Alcoholic Fatty Liver Disease (NAFLD).

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06024408

NCT06024408 | A Trial to Learn if Receiving ALN-PNP ... A Trial to Learn if Receiving ALN-PNP siRNA is Safe and Well Tolerated, and How it Works in Adult Participants With Nonalcoholic Fatty Liver Disease (NAFLD) ...