Idiopathic Pulmonary Fibrosis
Conditions
Brief summary
This study will be divided into 2 parts. Part 1 is a randomized, double-blind, single centre, placebo-controlled, single ascending dose (SAD) phase I study designed to assess the safety, tolerability, PK and PD (Pharmacodynamic) of TD139 in up to 36 healthy male subjects. Part 2 will be a randomized, double-blind, multi-centre, placebo-controlled, multiple dose expansion cohort, designed to assess the safety, tolerability, PK and PD of TD139 in up to 24 male subjects and female subjects of non child-bearing potential with IPF.
Detailed description
Up to 6 cohorts of 6 subjects will be randomly assigned in a blinded fashion to receive either a single dose of TD139 or matching placebo via DPI (dry powder inhaler) in an ascending dose fashion. A single cohort of up to 24 patients will be randomly assigned in a blinded fashion to receive a single dose of TD139 or placebo via DPI once daily for 14 days in a 2:1 TD139 to placebo ratio. The dose of TD139 selected will be based on data from Part 1 and on pre-clinical efficacy and safety data.
Interventions
DRUGInhaled TD139
DPI Galectin-3 inhibitor
DRUGPlacebo
DPI placebo
Sponsors
Galecto Biotech AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
Part 1 Inclusion Criteria * Healthy male subjects aged between 18 and 55 years of age. * Male subject willing to use a condom, if applicable (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) from the Day 1 dose of study medication until 3 months afterwards. * Subject with a body weight of at least 50 kg and a body mass index (BMI) within the range of 18 35 kg/m2. BMI = Body weight (kg) / \[Height (m)\]2. * Subject with no clinically significant abnormal serum biochemistry, haematology and urine examination values within 28 days of the Day 1 dose of study medication. * Subject with a negative urinary drugs of abuse screen, determined within 28 days of the Day 1 dose of study medication, (N.B. a positive alcohol result may be repeated at the discretion of the Investigator). * Subject with negative human immunodeficiency virus (HIV) and hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results. * Subject with no clinically significant abnormalities in 12 lead ECG determined within 28 days of the Day 1 dose of study medication. * Subjects were non smokers or former smokers (having ceased smoking for at least 6 months). * Subjects with no clinically significant impairment in oxygen saturation. * Subject satisfied a medical examiner about their fitness to participate in the study. * Subject provided written informed consent to participate in the study. * Subject was available to complete the study (including all follow up visits). Confirmed at Baseline / Prior to First Dose: * Subject continued to meet all screening inclusion criteria. * Subject with a negative urinary drugs of abuse screen (including alcohol) prior to dosing.
Exclusion criteria
* A clinically significant illness or surgery within 8 weeks prior to the Day 1 dose of study medication. * Significant medical history that, in the Investigator's opinion, may have adversely affected participation. * History of allergy or significant adverse reaction to drugs similar to the investigational drug, to nicotine, or to cholinergic drugs or to any drugs with a similar chemical structure. * History of hypersensitivity (anaphylaxis, angioedema) to any drug. * Use of any drug known to induce or inhibit hepatic drug metabolism, within 30 days prior to the Day 1 dose of study medication. * Use of medications known to prolong QT/QTc interval within 14 days prior to the Day 1 dose of study medication. * Any clinically significant findings of physical examination or laboratory findings at screening. * A clinically significant history of drug or alcohol abuse. * Receipt of regular/over the counter medication within 14 days of the Day 1 dose of study medication that may have had an impact on the safety and objectives of the study (at the Investigator's discretion). * Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction. * Inability to communicate well with the Investigator (i.e., language problem, poor mental development or impaired cerebral function). * Participation in a New Chemical Entity clinical study within the previous 4 months or a marketed drug clinical study within the previous 3 months. (N.B. washout period between studies is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study). * Donation of 450 mL or more blood within the previous 3 months. Confirmed at Baseline / Prior to First Dose: * Development of any
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 0 - 30 days | Number of participants reporting Adverse Events from the date of first dose, until 30 days post first dose. |
Countries
United Kingdom
Participant flow
Recruitment details
A total of 60 subjects were randomised, 39 randomized to treatment, with 24 subjects in Part 1 and 15 subjects in Part 2.
Participants by arm
| Arm | Count |
|---|---|
| 0.15 mg TD139 (Part 1) 4 Healthy Subjects are administered a single dose of 0.15mg TD139 inhaled as a dry powder in a fasted state. Each cohort will include a dose leader volunteer to be dosed a day before the rest of the cohort, followed by the remaining 3 subjects who will be dosed approximately 24 hours later.
Inhaled TD139: DPI Galectin-3 inhibitor | 4 |
| 1.5 mg TD139 (Part 1) 4 Healthy Subjects are administered a single dose of 1.5mg TD139 inhaled as a dry powder in a fasted state. Each cohort will include a dose leader volunteer to be dosed a day before the rest of the cohort, followed by the remaining 3 subjects who will be dosed approximately 24 hours later.
Inhaled TD139: DPI Galectin-3 inhibitor | 4 |
| 3 mg TD139 (Part 1) 4 Healthy Subjects are administered a single dose of 3mg TD139 inhaled as a dry powder in a fasted state. Each cohort will include a dose leader volunteer to be dosed a day before the rest of the cohort, followed by the remaining 3 subjects who will be dosed approximately 24 hours later.
Inhaled TD139: DPI Galectin-3 inhibitor | 4 |
| 10 mg TD139 Part 1 4 Healthy Subjects are administered a single dose of 10mg TD139 inhaled as a dry powder in a fasted state. Each cohort will include a dose leader volunteer to be dosed a day before the rest of the cohort, followed by the remaining 3 subjects who will be dosed approximately 24 hours later.
Inhaled TD139: DPI Galectin-3 inhibitor | 4 |
| 20 mg TD139 Part 1 4 Healthy Subjects are administered a single dose of 20mg TD139 inhaled as a dry powder in a fasted state. Each cohort will include a dose leader volunteer to be dosed a day before the rest of the cohort, followed by the remaining 3 subjects who will be dosed approximately 24 hours later.
Inhaled TD139: DPI Galectin-3 inhibitor | 4 |
| 50 mg TD139 Part 1 4 Healthy Subjects are administered a single dose of 50mg TD139 inhaled as a dry powder in a fasted state. Each cohort will include a dose leader volunteer to be dosed a day before the rest of the cohort, followed by the remaining 3 subjects who will be dosed approximately 24 hours later.
Inhaled TD139: DPI Galectin-3 inhibitor | 4 |
| Placebo Part 1 12 Healthy Subjects are administered placebo inhaled as a dry powder in a fasted state. Each cohort will include a dose leader volunteer to be dosed a day before the rest of the cohort, followed by the remaining 3 subjects who will be dosed approximately 24 hours later.
Placebo: DPI placebo | 12 |
| 0.3 mg TD139 Part 2 5 Patients with IPF are administered a single dose of 0.3mg TD139 once daily for 14 days inhaled as a dry powder. | 5 |
| 3 mg TD139 Part 2 5 Patients with IPF are administered a single dose of 3mg TD139 once daily for 14 days inhaled as a dry powder. | 5 |
| 10 mg TD139 Part 2 5 Patients with IPF are administered a single dose of 10mg TD139 once daily for 14 days inhaled as a dry powder. | 5 |
| Placebo Part 2 9 Patients with IPF are administered placebo inhaled as a dry powder. | 9 |
| Total | 60 |
Baseline characteristics
| Characteristic | 1.5 mg TD139 (Part 1) | 3 mg TD139 (Part 1) | 10 mg TD139 Part 1 | 20 mg TD139 Part 1 | 50 mg TD139 Part 1 | Placebo Part 1 | 0.15 mg TD139 (Part 1) | 0.3 mg TD139 Part 2 | 3 mg TD139 Part 2 | 10 mg TD139 Part 2 | Placebo Part 2 | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 4 Participants | 5 Participants | 9 Participants | 22 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 12 Participants | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 38 Participants |
| Age, Continuous | 29.8 Years STANDARD_DEVIATION 6.8 | 39.3 Years STANDARD_DEVIATION 10.21 | 29.8 Years STANDARD_DEVIATION 2.06 | 30.8 Years STANDARD_DEVIATION 9.54 | 32.8 Years STANDARD_DEVIATION 9.91 | 35.6 Years STANDARD_DEVIATION 7.53 | 42.3 Years STANDARD_DEVIATION 9.07 | 69.0 Years STANDARD_DEVIATION 6.32 | 73.6 Years STANDARD_DEVIATION 5.86 | 79.2 Years STANDARD_DEVIATION 2.77 | 72.9 Years STANDARD_DEVIATION 4.59 | 50.2 Years STANDARD_DEVIATION 20.63 |
| Region of Enrollment United Kingdom | 4 participants | 4 participants | 4 participants | 4 participants | 4 participants | 12 participants | 4 participants | 5 participants | 5 participants | 5 participants | 9 participants | 60 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 12 Participants | 4 Participants | 4 Participants | 5 Participants | 5 Participants | 9 Participants | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 12 | 0 / 5 | 0 / 5 | 1 / 5 | 0 / 9 |
| other Total, other adverse events | 0 / 4 | 0 / 4 | 2 / 4 | 3 / 4 | 4 / 4 | 4 / 4 | 2 / 12 | 4 / 5 | 5 / 5 | 4 / 5 | 7 / 9 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 12 | 0 / 5 | 0 / 5 | 1 / 5 | 0 / 9 |
Outcome results
Primary
Number of Participants With Adverse Events
Number of participants reporting Adverse Events from the date of first dose, until 30 days post first dose.
Time frame: 0 - 30 days
Population: All subjects in Part 1 are included in the safety population. The safety population includes all subjects who received at least one dose of study treatment (TD139 or Placebo). Safety parameters are listed and summarised using descriptive statistics. No formal statistical analysis is planned.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.15 mg TD139 (Part 1) | Number of Participants With Adverse Events | 0 Participants |
| 1.5 mg TD139 (Part 1) | Number of Participants With Adverse Events | 0 Participants |
| 3 mg TD139 (Part 1) | Number of Participants With Adverse Events | 2 Participants |
| 10 mg TD139 Part 1 | Number of Participants With Adverse Events | 3 Participants |
| 20 mg TD139 Part 1 | Number of Participants With Adverse Events | 4 Participants |
| 50 mg TD139 Part 1 | Number of Participants With Adverse Events | 4 Participants |
| Placebo Part 1 | Number of Participants With Adverse Events | 2 Participants |
| 0.3 mg TD139 Part 2 | Number of Participants With Adverse Events | 4 Participants |
| 3 mg TD139 Part 2 | Number of Participants With Adverse Events | 5 Participants |
| 10 mg TD139 Part 2 | Number of Participants With Adverse Events | 4 Participants |
| Placebo Part 2 | Number of Participants With Adverse Events | 7 Participants |