Investigate the Safety, Tolerability and Pharmacokinetics of FBL-MTX

NCT ID: NCT05117593

Last Updated: 2021-11-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-28

Study Completion Date

2021-10-19

Brief Summary

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This is a prospective, single-center, randomized, double-blind, placebo-controlled, single-ascending dose (SAD) phase 1 study to evaluate the safety, tolerability and pharmacokinetics of FBL-MTX in healthy male and female subjects.

Detailed Description

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The product FBL-MTX consists of Methotrexate (MTX) encapsulating liposomes functionalized with a folate peptide (SP-DS3), which targets activated macrophages of rheumatoid arthritis (RA).

This is a prospective, single-center, randomized, double-blind, placebo-controlled, single-ascending dose (SAD) phase 1 study in healthy subjects.

This study is planned to investigate up to 4 dose levels of FBL-MTX. Each dose level will consist of 8 healthy male and female subjects (ratio 1:1, male:female) to have 6 subjects being administered FBL-MTX and 2 subjects being administered placebo (ratio 3:1, active:placebo).

The study is designed to meet the following objectives:

* Primary: To evaluate the safety and tolerability of FBL-MTX following single-ascending intravenous doses to healthy male and female subjects.
* Secondary: To investigate the PK of FBL-MTX following single-ascending intravenous doses to healthy male and female subjects.

Conditions

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Rheumatoid Arthritis

Keywords

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rheumatoid arthritis healthy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

A maximum of 4 dose levels (0.1 mg, 0.33 mg, 1 mg and 2.5 mg) is preplanned to be investigated in separate sequential cohorts. Each cohort will consist of 8 healthy male and female subjects (3 subjects of either sex on FBL-MTX, 1 of either sex on placebo).
Primary Study Purpose

OTHER

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Double-blind

Study Groups

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FBL-MTX

A single dose of FBL-MTX will be administered by slow intravenous injection in the morning, under fasted conditions.

A maximum of 4 dose levels (0.1 mg, 0.33 mg, 1 mg and 2.5 mg) are pre-planned.

Group Type EXPERIMENTAL

FBL-MTX

Intervention Type DRUG

FBL-MTX is available as sterile liposomal dispersion for injection at nominal dose strength of 1 mg/mL of methotrexate free base. The dose of 0.1 mg was selected as starting dose in the present study. Three subsequent FBL-MTX dose levels are pre-planned: 0.33 mg, 1 mg and 2.5 mg.

Placebo

A single dose of placebo will be administered by slow injection in the morning, under fasted conditions.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo will consist of sterile saline 0.9% NaCl solution.

Interventions

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FBL-MTX

FBL-MTX is available as sterile liposomal dispersion for injection at nominal dose strength of 1 mg/mL of methotrexate free base. The dose of 0.1 mg was selected as starting dose in the present study. Three subsequent FBL-MTX dose levels are pre-planned: 0.33 mg, 1 mg and 2.5 mg.

Intervention Type DRUG

Placebo

Placebo will consist of sterile saline 0.9% NaCl solution.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Signed informed consent prior to any study-mandated procedure.
2. Healthy male or female subjects aged between 18 and 55 years (inclusive) at Screening.
3. Body mass index (BMI) of 18.0 to 30.0 kg/m2 (inclusive) at Screening.
4. Ability to communicate well with the investigator, in a language understandable to the subject, and to understand and comply with the study requirements.
5. Systolic blood pressure (SBP) 100-140 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and pulse rate 50-90 bpm (inclusive), measured on the same arm after ≥5 min in the supine position, at Screening and on Day -1.
6. Estimated glomerular filtration rate calculated using the Cockcroft-Gault equation ≥ 90 mL/min at Screening.
7. A female subject of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1 and must agree to consistently and correctly use (from Screening, during the entire study, and for at least 6 months after investigational product administration) a highly effective method of contraception with a failure rate of ≤1% per year, be sexually inactive, or have a vasectomized partner. If a hormonal contraceptive is used, it must be initiated at least 1 month before the treatment administration.
8. A female subject of non-childbearing potential, must be post-menopausal (defined as 12 consecutive months with no menses without an alternative medical cause, confirmed by a follicle stimulating hormone \[FSH\] test), or must have a medical history of previous bilateral salpingectomy, bilateral salpingo-oophorectomy, hysterectomy, premature ovarian failure (confirmed by a specialist), XY genotype, Turner syndrome, or uterine agenesis.
9. A male subject must use adequate contraception (e.g., condom) from investigational product administration up to at least 6 months after, unless he is vasectomized or sexually inactive. In addition, the subject must ensure that his female partner of childbearing potential agrees to consistently and correctly use for the same period a highly effective method of contraception with a failure rate of ≤1% per year.
10. A male subject must agree to refrain from donation of semen from investigational product administration up to at least 6 months after.

Exclusion Criteria

1. Previous exposure to FBL-MTX.
2. Known hypersensitivity to MTX or any other FBL-MTX components.
3. Clinically relevant findings on physical examination at Screening or on Day -1.
4. Clinically relevant abnormalities on 12-lead ECG, measured after 5 min in a supine position, at Screening or on Day -1.
5. Clinically relevant abnormalities on chest X-ray at Screening.
6. Clinically relevant findings in clinical laboratory tests (hematology, clinical chemistry, and urinalysis) at Screening or on Day -1.
7. Pre-existing blood dyscrasias, such as bone marrow hypoplasia, leukopenia, thrombocytopenia or significant anemia.
8. QTc \> 450ms in male and \> 470ms in female.
9. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above the normal range.
10. Any medical condition, acute, ongoing, recurrent or chronic, that presents a potential risk to the participant and/or that may compromise the objectives of the study.
11. History of major medical or surgical disorders which, in the opinion of the investigator, are likely to interfere with the distribution, metabolism, or excretion of the investigational product.
12. History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator.
13. History of tuberculosis.
14. Presence of chronic or acute bacterial or viral infection.
15. History or presence of an autoimmune disorder.
16. History of known or suspected immunodeficiency syndrome
17. Stomatitis, ulcers of the oral cavity and known active gastrointestinal ulcer disease.
18. Any significant acute or chronic medical illness, including past or present liver disease.
19. Previous clinically relevant history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
20. Veins unsuitable for intravenous puncture on either arm (e.g., veins that are difficult to locate, access, or puncture, veins with a tendency to rupture during or after puncture).
21. Participation in a clinical study involving investigational product administration within 3 months prior to Screening or in more than 2 clinical studies within 1 year prior to Screening.
22. History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to Screening.
23. Excessive methylxanthines consumption, defined as ≥ 500 mg per day, at Screening.
24. Nicotine intake (e.g., smoking, nicotine patch, nicotine chewing gum, or electronic cigarettes) within 3 months prior to Screening and inability to refrain from nicotine intake from Screening up to End-of-Study (EOS).
25. Previous treatment with any prescribed medications or over-the-counter (OTC) medications (including herbal medicines such as St John's Wort, homeopathic preparations, vitamins, and minerals) within 3 weeks prior to investigational product administration.
26. Previous treatment with vaccines within 4 weeks prior to investigational product administration.
27. Loss of 250 mL or more of blood within 3 months prior to Screening.
28. Positive results from urine drug and alcohol screen at Screening or on Day -1.
29. Positive Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) and/or HCV antibodies at Screening.
30. Positive HIV serology results at Screening.
31. Pregnant or lactating woman.
32. Any other circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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SOLFARCOS - Pharmaceutical and Cosmetic Solutions Ltd

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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BlueClinical Phase I

Porto, , Portugal

Site Status

Countries

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Portugal

Other Identifiers

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FBL-MTX-101

Identifier Type: -

Identifier Source: org_study_id