Clinical trial NCT05129644: Single Dose Escalation Study of P1101 in Healthy Adult Male Subjects
Official title: Phase I, Randomized Double-Blind, Active Control, Single Dose Escalation Study of P1101 in Healthy Adult Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: P1101, phase 1, healthy volunteers
Lead sponsor: PharmaEssentia
Sponsor class: INDUSTRY
First posted: 2021-11-22
Enrollment: 48
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This was a single center, double-blind, randomized, active control, single dose escalation study, with P1101 (24, 48, 90, 180, 225, 270 mcg) as the test drug and Pegasys (180 ug) as the control drug.
Primary purpose: OTHER

Brief summary: This was a single-center, double-blind, randomized, active control, single dose escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) profiles of P1101 in 48 healthy volunteers.

Detailed description: The primary objectives were to determine the safety and tolerability of single ascending subcutaneous doses of P1101 and to determine the pharmacokinetics of P1101 in single ascending subcutaneous doses of P1101 in healthy male subjects.

The secondary objectives were to evaluate the occurrence of side effects in healthy subjects receiving either P1101 or PEGASYS; to compare the pharmacokinetic parameters for P1101 and PEGASYS; and to assess the effect of P1101 on the biomarkers 2',5' oligoadenylate synthetase and neopterin.

A total of 48 subjects were enrolled to receive subcutaneous injection of P1101 in the dose level of 24 , 48 , 90 , 180 , 225 , or 270 mcg or to receive subcutaneous injection of 180 mcg Pegasys.

Eligibility criteria: Main Inclusion Criteria:

1. Be healthy males, non-smokers, ≥18 and ≤45 years of age;
2. Able to attend all scheduled visits and to comply with all study procedures.

Main Exclusion Criteria:

1. Clinically significant illness or surgery within 4 weeks prior to dosing;
2. Any clinically significant abnormality or abnormal laboratory test results found during screening;
3. Positive test for hepatitis B, hepatitis C, or HIV at screening;
4. Clinically significant vital sign abnormalities at screening;
5. History of significant alcohol or drug abuse within one year prior to the screening visit;
6. History of severe allergic or hypersensitivity reactions;
7. Use of an investigational drug or participation in an investigational drug trial within the last 4 weeks;
8. Any clinically significant history or presence of neurological, cardiovascular, pulmonary, hematological, immunologic, metabolic or other uncontrolled systemic disease;
9. Clinically significant history or known presence of psychiatric disorders, including but not limited to depression, anxiety, and sleep disorders;
10. Body organ transplant and are taking immunosuppressants;
11. History of malignant disease;
12. History or presence of endocrine disorders;
13. History of coagulation disorders and blood dyscrasias;
14. Inability to comprehend the written consent form.

Primary outcomes:
measure: Adverse Event
timeFrame: Through study Day 35
measure: AUC of P1101 and Pegasys
timeFrame: Samples were collected within 1 hour pre-dose, and at 1, 3, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 240, 288, 336, 504, and 672 hours post-dose.
measure: AUC0-t of P1101 and Pegasys
timeFrame: Samples were collected within 1 hour pre-dose, and at 1, 3, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 240, 288, 336, 504, and 672 hours post-dose.
measure: Cmax of P1101 and Pegasys
timeFrame: Samples were collected within 1 hour pre-dose, and at 1, 3, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 240, 288, 336, 504, and 672 hours post-dose.
measure: Ct of P1101 and Pegasys
timeFrame: Samples were collected within 1 hour pre-dose, and at 1, 3, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 240, 288, 336, 504, and 672 hours post-dose.
measure: Tmax of P1101 and Pegasys
timeFrame: Samples were collected within 1 hour pre-dose, and at 1, 3, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 240, 288, 336, 504, and 672 hours post-dose.
measure: T½ of P1101 and Pegasys
timeFrame: Samples were collected within 1 hour pre-dose, and at 1, 3, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 240, 288, 336, 504, and 672 hours post-dose.
measure: λz (Ke) of P1101 and Pegasys
timeFrame: Samples were collected within 1 hour pre-dose, and at 1, 3, 6, 9, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 240, 288, 336, 504, and 672 hours post-dose.
Secondary outcomes:
measure: 2',5' oligoadenylate synthetase (OAS): Emax
timeFrame: Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose
measure: 2',5' oligoadenylate synthetase (OAS): Tmax
timeFrame: Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose
measure: 2',5' oligoadenylate synthetase (OAS): AUC0-t
timeFrame: Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose
measure: Neopterin: Emax
timeFrame: Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose
measure: Neopterin: Tmax
timeFrame: Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose
measure: Neopterin: AUC0-t
timeFrame: Samples were collected within 1 hour pre-dose and at 24, 48, 72, 96, 120, 168, 240, 336, 504, and 672 hours post-dose
Other outcomes:
measure: Immunogenicity
timeFrame: Samples were collected within 1 hour pre-dose, at 336 and 672 hours after dose administration
Locations:
city: Québec
country: Canada
facility: Anapharm
Study officials:
affiliation: Anapharm 5160, boul. Décarie, suite 800 Montréal, Québec, Canada, H3X 2H9
name: Richard Larouche, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huang YW, Qin A, Fang J, Wang TF, Tsai CW, Lin KC, Teng CL, Larouche R. Novel long-acting ropeginterferon alfa-2b: Pharmacokinetics, pharmacodynamics and safety in a phase I clinical trial. Br J Clin Pharmacol. 2022 May;88(5):2396-2407. doi: 10.1111/bcp.15176. Epub 2021 Dec 28.