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

A Randomized, Double-Blind, Placebo-Controlled, First-in-Human Study to Assess Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Single and Multiple Ascending Doses of FTX-101 After Subcutaneous Injection of FTX-101 in Healthy Male Subjects

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 Overview

• Status: Terminated
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: FTX-101; Drug: Placebo

Detailed Description

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
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Altasciences Clinical Kansas, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part B (MAD): Cohort B1; Once daily dose (as 1 or 2 SC injection[s]) of FTX-101 or placebo for 14 days in a 3:1 ratio	Drug: FTX-101; Lyophilized powder for subcutaneous injection; Drug: Placebo; Lyophilized powder for subcutaneous injection
Experimental: Part B (MAD): Cohort B2; Once daily dose (as 1 or 2 SC injection[s]) of FTX-101 or placebo for 14 days in a 3:1 ratio	Drug: FTX-101; Lyophilized powder for subcutaneous injection; Drug: Placebo; Lyophilized powder for subcutaneous injection
Experimental: Part B (MAD): Cohort B3; Once daily dose (as 1 or 2 SC injection[s]) of FTX-101 or placebo for 14 days in a 3:1 ratio	Drug: FTX-101; Lyophilized powder for subcutaneous injection; Drug: Placebo; Lyophilized powder for subcutaneous injection
Experimental: Part B (MAD): Cohort B4; Optional cohort to receive once daily dose (as 1 or 2 SC injection[s]) of FTX-101 or placebo for 14 days in a 3:1 ratio	Drug: FTX-101; Lyophilized powder for subcutaneous injection; Drug: Placebo; Lyophilized powder for subcutaneous injection
Experimental: Part A (SAD): Cohort A1; Single dose (as 1, 2 or 4 SC injection[s]) of FTX-101 or placebo in a 3:1 ratio	Drug: FTX-101; Lyophilized powder for subcutaneous injection; Drug: Placebo; Lyophilized powder for subcutaneous injection
Experimental: Part A (SAD): Cohort A2; Single dose (as 1, 2 or 4 SC injection[s]) of FTX-101 or placebo in a 3:1 ratio	Drug: FTX-101; Lyophilized powder for subcutaneous injection; Drug: Placebo; Lyophilized powder for subcutaneous injection
Experimental: Part A (SAD): Cohort A3; Single dose (as 1, 2 or 4 SC injection[s]) of FTX-101 or placebo in a 3:1 ratio	Drug: FTX-101; Lyophilized powder for subcutaneous injection; Drug: Placebo; Lyophilized powder for subcutaneous injection
Experimental: Part A (SAD): Cohort A4; Single dose (as 1, 2 or 4 SC injection[s]) of FTX-101 or placebo in a 3:1 ratio	Drug: FTX-101; Lyophilized powder for subcutaneous injection; Drug: Placebo; Lyophilized powder for subcutaneous injection
Experimental: Part A (SAD): Cohort A5; Single dose (as 1, 2 or 4 SC injection[s]) of FTX-101 or placebo in a 3:1 ratio	Drug: FTX-101; Lyophilized powder for subcutaneous injection; Drug: Placebo; Lyophilized powder for subcutaneous injection
Experimental: Part A (SAD): Cohort A6; Optional cohort to receive additional single ascending intermediate (lower) or equivalent dose (as 1, 2 or 4 SC injection[s]) of FTX-101 or placebo in a 3:1 ratio	Drug: FTX-101; Lyophilized powder for subcutaneous injection; Drug: Placebo; Lyophilized powder for subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of adverse events	Frequency of AE will be collected through AE monitoring.	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.	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.	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.	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.	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.	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.	Part A (SAD): Days 1, 2, 4, and 15; Part B (MAD): Days 1, 2, 5, 9, 14, 15, 17, and 29
Frequency of injection site reactions	Evaluation of pain, tenderness, erythema/redness, swelling/induration or itching at the injection site will be rated mild (Grade 1), moderate (Grade 2), Severe (Grade 3), or potentially life-threatening (Grade 4)	Part A (SAD): Days 1, 2, and 15; Part B (MAD): Days 1-14, and 28
Change in Columbia Suicide Severity Rating Scale (C-SSRS) score	Frequency of positive results for suicidality. The C-SSRS is a questionnaire designed for the assessment of suicidal ideation and behavior in adolescents and adults.	Part A (SAD): Days -1-4, and 15; Part B (MAD:) Days -1-17, and 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma AUC0-24 (Part B MAD)	Area under the concentration-time curve over the dosing interval	Days 1-2
Plasma Ctrough (Part B MAD)	Plasma trough observed concentrations, for Day 11 to Day 13	Days 11 to 13
Plasma Cmin,ss (Part B MAD)	Minimum observed concentration at steady state	Days 14-17
Plasma Cmax,ss (Part B MAD)	Peak or maximum observed concentration at steady state	Days 14-17
Plasma AUC0-τ (Part B MAD)	Area under the concentration-time curve over the dosing interval	Days 14-17
Plasma Tmax,ss (Part B MAD)	Time of maximum observed concentration at steady state	Days 14-17
Plasma Thalf (Part B MAD)	Terminal elimination half-life, calculated as ln(2)/λZ	Days 14-17
Plasma Cav (Part B MAD)	Average steady-state plasma drug concentration calculated as AUC0-τ/τ	Days 14-17
Plasma Fluctuation (Part B MAD)	The range of steady-state concentrations divided by the average concentration (Day 14 only)	Days 14-17
Plasma Swing (Part B MAD)	Degree of swing over a dosing interval, after the last dose of a multiple-dose regimen expressed as a percentage. Calculated as 100*(Cmax-Cmin/Cmin).	Days 14-17
Plasma Rac(Cmax) (Part B MAD)	Accumulation ratio evaluated by comparing Day 14 Cmax,ss to Day 1 Cmax	Days 1-2, and 14-17
Plasma Rac(AUC) (Part B MAD)	Accumulation ratio evaluated by comparing Day 14 AUC0-τ to Day 1 AUC0-24	Days 1-2, and 14-17
Plasma Cmax	Peak or maximum observed concentration	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	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)	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	Part A (SAD): Days 1-4
Plasma AUC0-last/∞ (Part A)	Relative percentage of AUC0-last with respect to AUC0-∞	Part A (SAD): Days 1-4
Plasma λz	Apparent elimination rate constant, estimated by linear regression of the terminal linear portion of the log concentration versus the time curve	Part A (SAD): Days 1-4; Part B (MAD): Day 14-17
Plasma CL/F (Part A)	Apparent clearance, calculated as Dose/AUC0-∞	Part A (SAD): Days 1-4
Plasma Vz/F (Part A)	Apparent volume of distribution, calculated as Dose/ λZ * AUC0-∞	Part A (SAD): Days 1-4
Plasma Thalf (Part A)	Terminal elimination half-life, calculated as ln (2)/λZ	Part A (SAD): Days 1-4
Plasma Cmax/D (Part A)	Dose-normalized Cmax, calculated as Cmax/dose	Part A (SAD): Days 1-4
Plasma AUC0-last/D (Part A)	Dose-normalized AUC0-last, calculated as AUC0-last/dose	Part A (SAD): Days 1-4
Plasma AUC0-∞/D (Part A)	Dose normalized AUC 0-∞, calculated as AUC0-∞/dose	Part A (SAD): Days 1-4
Plasma AUMC0-last (Part A)	Area under the moment curve (AUMC) from the time of dosing to the last measurable (positive) concentration	Part A (SAD): Days 1-4
Plasma AUMC∞ (Part A)	AUMC extrapolated to infinity, based on the last observed concentration	Part A (SAD): Days 1-4
Urine Ae(0-last)	Cumulative amount excreted over all time intervals (0 to Tlast), calculated as the sum of all amounts excreted from each interval (t1-t2)	Part A (SAD): Days 1-4; Part B (MAD): Days 1, 2, and 14-17
Urine fe	Fraction of unchanged drug excreted in urine during the time interval (expressed in %, calculated)	Part A (SAD): Days 1-4; Part B (MAD): Days 1, 2, and 14-17
Urine CLR	Renal Clearance (Ae(0-last)/ AUC0-last)	Part A (SAD): Days 1-4; Part B (MAD): Days 1, 2, and 14-17
Plasma CLss/F (Part B MAD)	Apparent clearance at steady state, calculated as Dose/AUC0-τ	Part B (MAD): Days 14-17
Plasma Vz/F (Part B MAD)	Apparent volume of distribution at steady state, calculated as Dose/ λZ * AUC0-τ	Part B (MAD): Days 14-17

Collaborators and Investigators

• Sponsor: Find Therapeutics
• Investigators: Principal Investigator: Martin K. Kankam, MD, PhD, MPH, FAPCR, Altasciences Clinical Kansas, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2024
• Primary Completion (Actual): April 17, 2025
• Study Completion (Actual): April 17, 2025

Study Registration Dates

• First Submitted: September 25, 2024
• First Submitted That Met QC Criteria: September 25, 2024
• First Posted (Actual): September 27, 2024

Study Record Updates

• Last Update Posted (Actual): June 18, 2025
• Last Update Submitted That Met QC Criteria: June 13, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: remyelination; myelin; plexin A1; neuropilin 1
• Other Study ID Numbers: FTX0101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No