A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ir-CPI in Healthy Male Subjects

NCT04653766 | Completed Phase 1 Results DMC

• 2 other identifiers: Clin_IrCPI_1012019-002305-22
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this First-in-Human study is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of Ir-CPI, a novel dual inhibitor of FXIIa and FXIa, following IV administration of single ascending doses in healthy male volunteers.

Conditions

Healthy

Keywords

Antithrombotic; Intrinsic coagulation pathway

Outcome Measures

Primary Outcomes (1)

• Measurement of the Safety Lab Parameter Activated Partial Thromboplastin Time (aPTT)

  These safety aPTT results were readily available to the PI for safety follow-up during and after the study drug administration. Safety aPTT was followed up "at the bedside" at regular time-points (as opposed to the PD biomarker aPTT, which was assessed by the central laboratory alongside the PK time-points). An aPTT ratio was calculated by dividing the aPTT value (in sec) of the specific time-point (aPTTt) by the baseline aPTT value (in sec) (aPTTbaseline) of the same participant (aPTT ratio = aPTTt/aPTTbaseline). The baseline time-point was considered as having an aPTT ratio of 1. Concerning the row titles, for example, Day 1 H02:00 corresponds to aPTT ratio results obtained on Day 1, 2 hours after the start of the infusion.

  At pre-dose (baseline), 2, 4, 6, 8, 12, 24, 48, 72 hours post-dose and at the discharge visit (Day 10 ± 2 days)

Secondary Outcomes (6)

• Measurement of the Maximum Plasma Concentration (Cmax) of Ir-CPI

  Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96, 144 hours (144 hours for Dose 4 only)

• Measurement of the Time to Reach Maximum Plasma Concentration (Tmax) of Ir-CPI

  Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96, 144 hours (144 hours for Dose 4 only)

• Measurement of the Area Under the Plasma Concentration-time Curve From Time Zero to 6h (AUC0-6) and From Time Zero to Time of Infinity (AUCinf)

  Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96, 144 hours (144 hours for Dose 4 only)

• Measurement of the Effect of Ir-CPI on the Activated Partial Thromboplastin Time (aPTT)

  Pre-dose (baseline), 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96 hours post-dose and at the discharge visit (Day 10 ± 2 days)

• Measurement of the Effect of Ir-CPI on Factor XI Activity

  Pre-dose (baseline), 0.5, 1, 1.5, 2, 4, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72, 96 hours post-dose and at the discharge visit (Day 10 ± 2 days)

Study Arms (5)

Ir-CPI - Dose 1

EXPERIMENTAL

Participants received a single intravenous dose of 1.5 mg/kg of Ir-CPI during 6 hours

Drug: Ir-CPI - Dose 1

Ir-CPI - Dose 2

EXPERIMENTAL

Participants received a single intravenous dose of 3.0 mg/kg of Ir-CPI during 6 hours

Drug: Ir-CPI - Dose 2

Ir-CPI - Dose 3

EXPERIMENTAL

Participants received a single intravenous dose of 6.0 mg/kg of Ir-CPI during 6 hours

Drug: Ir-CPI - Dose 3

Ir-CPI - Dose 4

EXPERIMENTAL

Participants received a single intravenous dose of 9.0 mg/kg of Ir-CPI during 6 hours

Drug: Ir-CPI - Dose 4

Placebo

PLACEBO COMPARATOR

Participants received a single intravenous dose of placebo during 6 hours

Drug: Placebo

Interventions

Ir-CPI - Dose 1 DRUG

6 participants received a single intravenous dose of 1.5 mg/kg of Ir-CPI during 6 hours

Ir-CPI - Dose 1

Ir-CPI - Dose 2 DRUG

6 participants received a single intravenous dose of 3.0 mg/kg of Ir-CPI during 6 hours

Ir-CPI - Dose 2

Ir-CPI - Dose 3 DRUG

6 participants received a single intravenous dose of 6.0 mg/kg of Ir-CPI during 6 hours

Ir-CPI - Dose 3

Ir-CPI - Dose 4 DRUG

6 participants received a single intravenous dose of 9.0 mg/kg of Ir-CPI during 6 hours

Ir-CPI - Dose 4

Placebo DRUG

For each dose group, 2 additional participants received a single intravenous dose of placebo during 6 hours (8 in total).

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Have given written informed consent approved by the relevant Ethics Committee (EC) governing the site, indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
• Male participants between 18 and 55 years of age, inclusive at screening.
• Otherwise healthy with no clinically significant abnormalities as determined by medical history, physical examination, blood chemistry assessments, haematological assessments, coagulation and urinalysis, measurement of vital signs, and ECG. Isolated out-of-range values judged by the PI (or designated physician) to be of no clinical significance can be allowed. This determination must be recorded in the participant's source documents.
• Have a body weight in the range of 50 to 90 kg inclusive at screening. Have a body mass index (BMI) of 19 to 28 kg/m2 inclusive at screening.
• Agree to abstain from alcohol intake 24 hours before administration of study drug, during the in-patient period of the study and 24 hours prior to all other ambulatory visits, up until and including the discharge visit.
• Agree not to use prescription medications within 14 days prior to study drug administration and through the duration of the study, unless approved by the PI and Sponsor medical monitor.
• Non-smokers or abstinence from tobacco or nicotine-containing products for at least 3 months prior to screening.

You may not qualify if:

• Venous access (both arms) sufficient to allow blood sampling and study drug administration as per protocol.
• Participants and their partners of childbearing potential \[meaning who are not surgically sterile (tubal ligation/obstruction or removal of ovaries or uterus) or post-menopausal (absence of menstrual periods for at least 12 consecutive months)\] must be willing to use 2 methods of contraception: - a highly effective method of birth control starting at screening. Highly effective methods of birth control are defined as those that result in a low failure rate (i.e. Pearl Index less than 1% per year) when used consistently and correctly, such as implants, rings, patches, injectable or combined oral contraceptives, intrauterine devices (IUDs), or sexual abstinence (periodic abstinence e.g. calendar, ovulation, symptothermal, postovulation methods, declaration of abstinence for the duration of the trial, and withdrawal are not acceptable methods of contraception) . - and a local barrier form of contraception. Acceptable barrier methods are either the participant's use of a condom or the partner's use of an occlusive cap or diaphragm, or spermicides. Participants will not donate sperm from the selection visit and up to 90 days after the infusion. In case of sterile or vasectomised participants, no contraception will be required for their partners of childbearing potential.
• Willing/able to adhere to the study visit schedule and other requirements, prohibitions and restrictions specified in this protocol.
• Currently have or have a history of any clinically significant medical illness or medical disorders the PI considers should exclude the participant, including (but not limited to) cardiovascular disease, neuromuscular, haematological disease, immune deficiency state, respiratory disease, hepatic or gastrointestinal disease, neurological or psychiatric disease, ophthalmological disorders, neoplastic disease, renal or urinary tract diseases, or dermatological disease.
• History of personal or familial bleeding disorders; including prolonged or unusual bleeding.
• History of deficiency in factor XII (FXII) or haemophilia type A (FVII) or type B (FIX) or type C (FXI).
• History of cerebral bleeding (e.g. after a car accident), stroke and cerebrovascular accident (CVA).
• Anamnestic history of Lyme disease or tick-borne encephalitis.
• Use of Acetylsalicylic-Acid (ASA)-containing OTC medications within 1 month prior to screening.
• Chronic administration of NSAIDs, chronic use of corticosteroids within 1 month prior to screening.
• Chronic administration of clopidogrel, ticlopidin, dipyridamole, Coumadin-like anticoagulants, new oral anticoagulant dabigatran, rivaroxaban, apixaban or edoxaban within 3 months prior to screening.
• Administration of unfractionated heparin, low molecular weight heparin, fibrinolytic agents and anti-FXa within 3 months prior to screening.
• Have an active acute or chronic infection or diagnosed latent infection.
• Systolic blood pressure (SBP) greater than 150 or less than 90 mmHg, diastolic blood pressure (DBP) greater than 90 or less than 50 mmHg, and heart rate (HR) greater than 100 or less than 40 bpm.
• Acute clinically relevant illness within 7 days prior to study drug administration or have had a major illness or hospitalisation within 1 month prior to study drug administration.

Sponsors & Collaborators

• Bioxodes S.A.: lead

Study Sites (1)

A.T.C. Pharma

Liège, 4000, Belgium

Location

Results Point of Contact

• Title: Medical Writer
• Organization: Bioxodes

stephanie.demoulin@bioxodes.com

+32 (0)71 239 602

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2020
• First Posted: December 4, 2020
• Study Start: September 12, 2019
• Primary Completion: July 18, 2020
• Study Completion: January 4, 2023
• Last Updated: February 23, 2023
• Results First Posted: May 27, 2021

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)