SAD and MAD Study of FTX-101 in Healthy Male Subjects

Phase 1TerminatedNCT06617546

Find Therapeutics49 enrolled

Overview

This is a Phase 1, first-in-human (FIH), single-center, randomized, double-blind, placebo-controlled study in healthy male subjects. The study will include the following 2 parts: * Part A: Single Ascending Dose (SAD) in healthy male subjects * Part B: Multiple Ascending Dose (MAD) in healthy male subjects

Study Rationale: FTX-101 is a first-in-class, synthetic peptide with a novel mechanism of action designed to promote the self-repair of myelin. FTX-101 is a highly selective modulator of the PlexinA1/Neuropilin 1 receptor system and displays no significant activity on any other target. FTX-101 interferes with the heterodimerization of the coreceptor system and, ultimately, with the activation of second messenger signaling pathways shown to inhibit both the differentiation and migration of oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs). Through this mechanism, FTX-101 disinhibits both the differentiation of OPCs to OLs and migration of OPCs into lesions, favorably promoting the remyelination process. The study is designed to evaluate the safety, tolerability and pharmacokinetic profile of single ascending doses and multiple ascending doses of FTX-101 subcutaneous injection in healthy male subjects. The study will characterize the pharmacokinetics of FTX-101 following SAD and MAD SC injection of FTX-101. The study will also evaluate the immunogenic potential of FTX-101 and will also explore the relationship between FTX-101 concentration and the change from baseline corrected QT interval. Detailed Description: This is a Phase 1, first-in-human (FIH), single-center, randomized, double-blind, placebo-controlled study in healthy male subjects. The study will include the following 2 parts: * Part A: SAD in healthy male subjects * Part B: MAD in healthy male subjects Part A - SAD: Part A consists of 5 planned cohorts (A1 to A5) of 8 healthy adult male subjects each. An additional SAD intermediate (lower) or equivalent dose cohort (A6) of 8 male subjects may be added at the discretion of the Sponsor. In each cohort, subjects will be randomized to receive a single subcutaneous (SC) dose (as 1, 2 or 4 injection\[s\]) of either FTX-101 or placebo in a 3:1 (FTX-101: placebo) ratio to have a total of 6 subjects receiving FTX-101 and 2 subjects receiving placebo. Part B - MAD: Part B consists of 3 planned cohorts (B1 to B3) of 8 healthy adult male subjects each. An additional MAD cohort (B4) of 8 male subjects may be added at the discretion of the Sponsor depending on emerging safety and plasma PK data from the previous cohort(s). The proposed dosing regimen (dose level and frequency) for the first cohort (B1) in Part B (MAD) will be based on available safety, tolerability, and PK data from Part A (SAD). The dosing regimens for each subsequent cohort in Part B will be determined based on the available blinded safety, tolerability, and PK data from Part A and any previous cohorts in Part B. In each cohort, subjects will be randomized to receive multiple SC doses of either FTX-101 or placebo in a 3:1 (FTX-101: placebo) ratio to have a total of 6 subjects receiving FTX-101 and 2 subjects receiving placebo.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Enrollment

Conditions

Healthy Volunteers

Interventions

FTX-101DRUG

Lyophilized powder for subcutaneous injection

PlaceboDRUG

Lyophilized powder for subcutaneous injection

Eligibility

Sex: MALEMin age: 18 YearsMax age: 59 YearsHealthy volunteers:

Medical Language ↔ Plain English

Key Inclusion Criteria: * Willingness to comply with all study procedures and availability for the duration of the study * Healthy adult male * Aged at least 18 years but not older than 59 years * Body mass index (BMI) within 18.5 kg/m\^2 to 32.0 kg/m\^2, inclusively * Non- or ex-smoker * Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination (including vital signs) and/or ECG. Key Exclusion Criteria: * Supine or semi-supine pulse rate less than 45 beats per minute (bpm) or more than 100 bpm * Supine or semi-supine blood pressure below 90/50 mmHg * Supine or semi-supine blood pressure higher than 150/95 mmHg * History of significant hypersensitivity to FTX-101 or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs * Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability * History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease * Showing suicidal tendency from 6 months prior to screening * Presence of out-of-range cardiac intervals at screening defined as: * PR \< 110 msec, PR \> 200 msec * QRS \< 60 msec, QRS \>110 msec) * QT Interval Corrected for Heart Rate using Fridericia's Correction Formula (QTcF): • \> 450 msec * History of additional risk factors for torsade's de pointes * Use of concomitant medications that prolong the QT/ corrected QT (QTc) interval * Current use (in the last 6 months) of alcohol (\> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic) * Any history of substance or alcohol use disorder within the past 2 years and/or current maintenance therapy (within the past 2 years) for treatment of substance use disorder * Use of any prescription drugs in the 28 days or 5 half-lives, whichever is longer, prior to the first study treatment administration, that in the opinion of an investigator would put into question the status of the participant as healthy * Use of St. John's wort in the 28 days prior to the first study treatment administration * Positive screening results to HIV Ag/Ab combo, hepatitis B surface Ag or hepatitis C virus tests * Intake of an investigational product (IP) in the 28 days prior to the first study treatment administration or within 5 times the elimination half-life of the IP, whichever is longer * Donation of plasma in the 7 days prior to the first study treatment administration * Donation of 1 unit of blood to American Red Cross or equivalent organization or donation of over 500 mL of blood in the 56 days prior to the first study treatment administration

Locations (1)

Altasciences Clinical Kansas, Inc.

Overland Park, Kansas, United States

Outcomes

Primary Outcomes

Frequency of adverse events

Frequency of AE will be collected through AE monitoring.

Time frame: Part A (SAD): Days -1-15; Part B (MAD): Days -1-28

Severity of adverse events

Severity of AE will be collected through AE monitoring. AEs will be graded per the current National Cancer Institute's Common Terminology Criteria for Adverse Events.

Time frame: Part A (SAD): Days -1-15; Part B (MAD): Days -1-28

Number of patients with a change in general biochemistry, hematology, coagulation and urinalysis clinical laboratory parameters

Frequency of abnormal general biochemistry, hematology, coagulation, and urinalysis clinical laboratory values.

Time frame: Part A (SAD): Days -1, 4 and 15; Part B (MAD): Days -1, 5, 9, 13, 17, 28

Number of patients with a change in vital signs

Frequency of abnormal vital sign measurements.

Time frame: Part A (SAD): Days -1-4 and 15; Part B (MAD): Days -1-17 and 28

Number of patients with a change in 12-lead safety electrocardiogram (ECG)

Frequency of abnormal 12-lead ECG parameters including PR, RR, QRS, QT and QTcF.

Time frame: Part A (SAD): Days -1-2, and 15; Part B (MAD): Days -1, 1, 3, 5, 7, 9, 11, 14, 28

Number of patients with a change in physical examination findings

Frequency of abnormal physical examination findings.

Time frame: Part A (SAD): Days -1-4, and 15; Part B (MAD): Days -1-17, 28

Number of patients with a change in neurological examination findings

Frequency of abnormal neurological examination findings.

Data from ClinicalTrials.gov

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Secondary Outcomes

Plasma Cmax

Peak or maximum observed concentration

Time frame: Part A (SAD): Days 1-4; Part B (MAD): Days 1-2

Plasma Tmax

Time of maximum observed concentration. If the maximum observed concentration is not unique, then the first maximum is used

Time frame: Part A (SAD): Days 1-4; Part B (MAD): Days 1-2

Plasma AUC0-last

Area under the concentration-time curve from dosing to the time of last quantifiable concentration (Tlast)

Time frame: Part A (SAD): Days 1-4; Part B (MAD): Days 1-2

Plasma AUC0-∞ (Part A)

Area under the concentration time curve extrapolated to infinity, calculated as AUClast + Clast/λZ, where Clast is the last quantifiable concentration at time Tlast