A Trial to Learn if ALN-PNP is Safe and Well Tolerated in Adult Healthy Participants

Sponsor

Regeneron Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05648214

Collaborator

(none)

Enrollment

Location

Arms

11.6

Anticipated Duration (Months)

5.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of the study is to evaluate the safety and tolerability of single doses of ALN-PNP in healthy adult participants.

The secondary objectives of the study are to:

Characterize single dose pharmacokinetics (PK) of ALN-PNP and potential major metabolite(s) in adult participants
Assess the immunogenicity of ALN-PNP following single dose administrations
Explore the effects of ALN-PNP on circulating blood lipid profile

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: ALN-PNP Drug: Placebo (PB)	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

64 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 1, Randomized, Double-blind, Placebo-Controlled, Single Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of ALN-PNP, an siRNA Targeting PNPLA3, in Healthy Adult Participants

Actual Study Start Date :

Dec 27, 2022

Anticipated Primary Completion Date :

Dec 15, 2023

Anticipated Study Completion Date :

Dec 15, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALN-PNP Dose 1 or PB 8 participants, randomized 6:2	Drug: ALN-PNP Solution for subcutaneous (SC) injection Drug: Placebo (PB) matching placebo, solution for SC injection
Experimental: ALN-PNP Dose 2 or PB 8 participants, randomized 6:2	Drug: ALN-PNP Solution for subcutaneous (SC) injection Drug: Placebo (PB) matching placebo, solution for SC injection
Experimental: ALN-PNP Dose 3 or PB 8 participants, randomized 6:2	Drug: ALN-PNP Solution for subcutaneous (SC) injection Drug: Placebo (PB) matching placebo, solution for SC injection
Experimental: ALN-PNP Dose 4 or PB 8 participants, randomized 6:2	Drug: ALN-PNP Solution for subcutaneous (SC) injection Drug: Placebo (PB) matching placebo, solution for SC injection
Experimental: ALN-PNP Dose 5 or PB 8 participants, randomized 6:2	Drug: ALN-PNP Solution for subcutaneous (SC) injection Drug: Placebo (PB) matching placebo, solution for SC injection
Experimental: Optional ALN-PNP Dose 5 or PB 8 participants, randomized 6:2 This is an optional cohort, if there is a need for additional dose characterization of ALN-PNP.	Drug: ALN-PNP Solution for subcutaneous (SC) injection Drug: Placebo (PB) matching placebo, solution for SC injection
Experimental: JPN ALN-PNP Dose 4 or PB 8 Japanese participants only, randomized 6:2	Drug: ALN-PNP Solution for subcutaneous (SC) injection Drug: Placebo (PB) matching placebo, solution for SC injection
Experimental: JPN ALN-PNP Dose 5 mg or PB 8 Japanese participants only, randomized 6:2	Drug: ALN-PNP Solution for subcutaneous (SC) injection Drug: Placebo (PB) matching placebo, solution for SC injection

Outcome Measures

Primary Outcome Measures

Incidence of treatment-emergent adverse events (TEAEs) [Through end of study, approximately Day 169]
A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.
Incidence of TEAEs by severity [Through end of study, approximately Day 169]
The severity of AEs will be graded according to the following scale: Mild: Does not interfere in a significant manner with the participant normal functioning level. It may be an annoyance. Prescription drugs are not ordinarily needed for relief of symptoms, but may be given because of personality of the participant. Moderate: Produces some impairment of functioning but is not hazardous to health. It is uncomfortable or an embarrassment. Treatment for symptom may be needed. Severe: Produces significant impairment of functioning or incapacitation and is a definite hazard to the participant's health. Treatment for symptom may be given and/or participant hospitalized.

Secondary Outcome Measures

Concentration of ALN-PNP and potential major metabolite(s) in plasma over time [Through end of study, approximately Day 169]
Incidence of ALN-PNP antidrug-antibodies (ADA) over time [Through end of study, approximately Day 169]
Titer of ALN-PNP ADA over time [From dosing, at Day 1 to study end at Day 169]
Change from baseline in low-density lipoprotein (LDL) in adult participants [Through end of study, approximately Day 169]
Change from baseline in high-density lipoprotein (HDL) in adult participants [Through end of study, approximately Day 169]
Change from baseline in triglyceride (TG) in adult participants [Through end of study, approximately Day 169]
Change from baseline in apolipoprotein B (ApoB) in adult participants [Through end of study, approximately Day 169]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Key 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
Be living <10 years outside of Japan
Has a body mass index between 18 and 32 kg/m^2, inclusive, at the screening visit
Is judged by the investigator to be in good health, as described in the protocol
Is in good health based on laboratory safety testing obtained at the screening visit and approximately within 24 hours prior to administration of study drug

Key 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
Using the Modification of Diet in Renal Disease equation, has a glomerular filtration rate as described in the protocol at the screening visit
Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin above the upper limit of normal (ULN) range.
Is a current smoker or former smoker, including e-cigarettes, who stopped smoking within 3 months prior to the screening visit
Has a history of alcohol or drug abuse per investigator opinion
Is positive for hepatitis C antibody and if so, positive for qualitative (ie, detected or not detected) hepatitis C virus ribonucleic acid (RNA) test at the screening visit