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

Find Therapeutics

Status and phase: Terminated; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: Placebo; Drug: FTX-101

Study type: Interventional

Funder types: Industry

Identifiers

NCT06617546

FTX0101

Details and patient eligibility

About

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

Full 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.

Enrollment: 49 patients

Sex: Male

Ages: 18 to 59 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

---

49 participants in 10 patient groups

Part A (SAD): Cohort A1

Experimental group

Description:

Single dose (as 1, 2 or 4 SC injection\[s\]) of FTX-101 or placebo in a 3:1 ratio

Treatment:

Drug: FTX-101

Drug: Placebo

Part A (SAD): Cohort A2

Experimental group

Description:

Single dose (as 1, 2 or 4 SC injection\[s\]) of FTX-101 or placebo in a 3:1 ratio

Treatment:

Drug: FTX-101

Drug: Placebo

Part A (SAD): Cohort A3

Experimental group

Description:

Single dose (as 1, 2 or 4 SC injection\[s\]) of FTX-101 or placebo in a 3:1 ratio

Treatment:

Drug: FTX-101

Drug: Placebo

Part A (SAD): Cohort A4

Experimental group

Description:

Single dose (as 1, 2 or 4 SC injection\[s\]) of FTX-101 or placebo in a 3:1 ratio

Treatment:

Drug: FTX-101

Drug: Placebo

Part A (SAD): Cohort A5

Experimental group

Description:

Single dose (as 1, 2 or 4 SC injection\[s\]) of FTX-101 or placebo in a 3:1 ratio

Treatment:

Drug: FTX-101

Drug: Placebo

Part A (SAD): Cohort A6

Experimental group

Description:

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

Treatment:

Drug: FTX-101

Drug: Placebo

Part B (MAD): Cohort B1

Experimental group

Description:

Once daily dose (as 1 or 2 SC injection\[s\]) of FTX-101 or placebo for 14 days in a 3:1 ratio

Treatment:

Drug: FTX-101

Drug: Placebo

Part B (MAD): Cohort B2

Experimental group

Description:

Once daily dose (as 1 or 2 SC injection\[s\]) of FTX-101 or placebo for 14 days in a 3:1 ratio

Treatment:

Drug: FTX-101

Drug: Placebo

Part B (MAD): Cohort B3

Experimental group

Description:

Once daily dose (as 1 or 2 SC injection\[s\]) of FTX-101 or placebo for 14 days in a 3:1 ratio

Treatment:

Drug: FTX-101

Drug: Placebo

Part B (MAD): Cohort B4

Experimental group

Description:

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

Treatment:

Drug: FTX-101

Drug: Placebo