Clinical trial NCT05905068: Adult Subjects With Elevated Low-Density Lipoprotein-Cholesterol to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects
Official title: A Phase 1, Randomized, Single-blinded, Placebo-controlled, Single-ascending-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of RN0191 in Adult Subjects With Elevated Low-Density Lipoprotein-Cholesterol
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: To Reduce the LDL-C Level in Hypercholesteremia Adult Patients
Combination for Subgroup High LDL-c Patients With Other Comorbidities
Lead sponsor: Ikaria Bioscience Pty Ltd
Sponsor class: INDUSTRY
First posted: 2023-06-15
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is a randomized, placebo-controlled, single ascending-dose (SAD) study of RN0191 administered SC to adult subjects with elevated low-density lipoprotein-cholesterol. Subjects who have signed an Ethics Committee (EC)-approved informed consent form (ICF) and have met all the protocol eligibility criteria during screening may be enrolled into the study. In this SAD study, adult subjects with elevated LDL-C will be enrolled in up to 4 cohorts. Each cohort will comprise 8 subjects randomized in a 3:1 ratio (1:1 ratio for sentinel subjects; 5:1 ratio for non-sentinel subjects) to receive a single dose of RN0191 (n=6) or placebo (n=2), respectively.
Primary purpose: TREATMENT

Brief summary: Objectives: The primary and secondary objectives of the study are presented below. Exploratory objectives are presented in the body of the protocol.

Primary:

• To determine the safety and tolerability of RN0191 administered as escalating single subcutaneously (SC) doses in adult subjects with elevated low-density lipoprotein-cholesterol

Secondary:

* To evaluate the single-dose pharmacokinetics (PK) of RN0191 in adult subjects with elevated low-density lipoprotein-cholesterol
* To evaluate the pharmacodynamic (PD) effect of RN0191 on serum levels of low-density lipoprotein-cholesterol (LDL-C)
* To evaluate the PD effect of RN0191 on plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9)

Detailed description: This is a randomized, placebo-controlled, single ascending-dose (SAD) study of RN0191 administered SC to adult subjects with elevated low-density lipoprotein-cholesterol. Subjects who have signed an Ethics Committee (EC)-approved informed consent form (ICF) and have met all the protocol eligibility criteria during screening may be enrolled into the study. The study only has one part: SAD cohorts with Sentinel Dosing

The starting dose for subjects in Cohort 1 will be 25 mg RN0191 (or placebo). The following are the planned dose levels for subsequent cohorts in the SAD phase:

* Cohort 2: 100 mg RN0191 or placebo
* Cohort 3: 300 mg RN0191 or placebo
* Cohort 4: 500 mg RN0191 or placebo

Eligibility criteria: Inclusion Criteria:

1. Male and female subjects, aged 18 to 60 years, inclusive.
2. Body mass index between 18 and 32 kg/m2, inclusive, with body weight \> 45 kg for females and \>50 kg for males.
3. Serum LDL-C ≥100mg/dL (2.6 mmol/L) at screening and Day -1.
4. Fasting triglycerides \< 400 mg/dL (\<4.52 mmol/L) at screening and Day -1.
5. Adequate complete blood counts (complete blood counts \[CBCs\]; if outside the reference range, CBC values that are not clinically relevant and are acceptable to the Investigator)
6. Female subjects are eligible to participate if they are confirmed either not women of child-bearing potential (WOCBP), or have a negative urine pregnancy test at Day 1, are not breastfeeding, and willing and able to abide by the contraception guidelines.
7. Male subjects who can produce viable sperm are eligible to participate if they agree to use an adequate method of contraception as per the contraceptive guidance from Screening (signing the ICF) until at least 3 months post dose. Subjects with a partner(s) who is (are) not of childbearing potential are exempt from these requirements.
8. Male subjects with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile penetration. In addition, male subjects must refrain from donating sperm from Screening (signing the ICF) until at least 3 months post dose.
9. Willing to comply with protocol required visit schedule and visit requirements and provide written informed consent

Exclusion Criteria:

1. Male and female subjects, aged 18 to 60 years, inclusive.
2. Body mass index between 18 and 32 kg/m2, inclusive, with body weight \> 45 kg for females and \>50 kg for males .
3. Serum LDL-C ≥100mg/dL (2.6 mmol/L) at screening and Day -1.
4. Fasting triglycerides \< 400 mg/dL (\<4.52 mmol/L) at screening and Day -1.
5. Adequate complete blood counts (complete blood counts \[CBCs\]; if outside the reference range, CBC values that are not clinically relevant and are acceptable to the Investigator).
6. Female subjects are eligible to participate if they are confirmed either not women of child-bearing potential (WOCBP), or have a negative urine pregnancy test at Day 1, are not breastfeeding, and willing and able to abide by the contraception guidelines (signing the ICF).
7. Male subjects who can produce viable sperm are eligible to participate if they agree to use an adequate method of contraception as per the contraceptive guidance in Appendix 3 from Screening (signing the ICF) until at least 3 months post dose. Subjects with a partner(s) who is (are) not of childbearing potential are exempt from these requirements.
8. Male subjects with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile penetration. In addition, male subjects must refrain from donating sperm from Screening (signing the ICF) until at least 3 months post dose.
9. Willing to comply with protocol required visit schedule and visit requirements and provide written informed consent.

Primary outcomes:
measure: Exploratory objectives are presented in the body of the protocol.
timeFrame: For each subject in the study, the duration of the study clinic visits is approximately 21 weeks from screening to Day 85/EOS examination.
Secondary outcomes:
Other outcomes:
Locations:
city: Herston
country: Australia
facility: Nucleus Networks
state: Brisbane
Study officials:
affiliation: Nucleus Network
name: Kristi McLendon, MD
role: PRINCIPAL_INVESTIGATOR
References: