TD-1058 First-In-Human Study in Healthy Subjects and Subjects With Idiopathic Pulmonary Fibrosis

NCT04589260 | Terminated Phase 1

• 2 other identifiers: 01852020-003003-34
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, 4-part, randomized, double-blinded, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TD-1058 inhaled solution. Part A is a SAD study in healthy subjects, Part B is a MAD study in healthy subjects, Part C is a multiple-dose study in subjects with IPF, and Part D studies lung bioavailability and renal elimination in Healthy Subjects.

Conditions

Idiopathic Pulmonary Fibrosis (IPF)

Keywords

IPF; Idiopathic Pulmonary Fibrosis; Pulmonary Fibrosis; Fibrosis; Lung diseases, interstitial

Outcome Measures

Primary Outcomes (4)

• Part A (SAD) - Adverse Events

  Number and severity of treatment emergent adverse events

  Part A (SAD) Day 1 to Day 8

• Part B (MAD) - Adverse Events

  Number and severity of treatment emergent adverse events

  Part B (MAD) Day 1 to Day 21

• Part C (IPF) - Adverse Events

  Number and severity of treatment emergent adverse events

  Part C (IPF) Day 1 to Day 35

• Part D (Microtracer) - Adverse Events

  Number and severity of treatment emergent adverse events

  Part D (Microtracer) Day 1 to Day 8

Secondary Outcomes (3)

• Pharmacokinetics (PK) of TD-1058: AUC

  Part A (SAD) Day 1 to Day 8 Part B (MAD) Day 1 to Day 21 Part C (IPF) Day 1 to Day 35 Part D (Microtracer) Day 1 to Day 8

• Pharmacokinetics (PK) of TD-1058: Cmax

  Part A (SAD) Day 1 to Day 8 Part B (MAD) Day 1 to Day 21 Part C (IPF) Day 1 to Day 35 Part D (Microtracer) Day 1 to Day 8

• Pharmacokinetics (PK) of TD-1058: Tmax

  Part A (SAD) Day 1 to Day 8 Part B (MAD) Day 1 to Day 21 Part C (IPF) Day 1 to Day 35 Part D (Microtracer) Day 1 to Day 8

Study Arms (2)

TD-1058

EXPERIMENTAL

Part A (SAD): 6 out of 8 subjects per cohort (up to 5 cohorts) will be randomized to receive a single dose of TD-1058 Part B (MAD): 6 out of 8 subjects per cohort (up to 4 cohorts) will be randomized to receive multiple dose of TD-1058 Part C (IPF subjects): 8 out of 12 subjects per cohort (up to 2 cohorts) will be randomized to receive multiple dose of TD-1058 Part D (Healthy Subjects): 6 subjects (1 cohort) will receive a single dose of TD-1058. After receipt of initial dose, subjects will recieve infusion of radiolabeled TD-1058 microtracer.

Drug: TD-1058

Placebo

PLACEBO COMPARATOR

Part A (SAD): 2 out of 8 subjects per cohort (up to 5 cohorts) will be randomized to receive a single dose of placebo Part B (MAD): 2 out of 8 subjects per cohort (up to 4 cohorts) will be randomized to receive multiple dose of placebo Part C (IPF subjects): 4 out of 12 subjects per cohort (up to 2 cohorts) will be randomized to receive multiple dose of placebo

Drug: Placebo

Interventions

TD-1058 DRUG

Study drug to be administered by oral inhalation

TD-1058

Placebo DRUG

Placebo to be administered by oral inhalation

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Parts A and B:
• Healthy, adult, male or female, 18 to 60 years of age, inclusive, at Screening
• Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2 and weighs at least 50 kg at Screening
• Medically healthy with no clinically significant medical history, physical examination, spirometry, vital signs or ECGs, as deemed by the Investigator or designee
• Forced expiratory volume of 1 second (FEV1) ≥80% predicted at Screening and prior to dosing
• No clinically significant abnormalities in the results of laboratory evaluations at Screening and the visit scheduled between Day -7 and Day -2, as applicable, and at the discretion of the Investigator and Sponsor's Medical Monitor.
• Pregnancy concerns:
• Female subjects must either of non-childbearing potential or if of childbearing potential, subject must not be pregnant or breastfeeding, and must agree to use a highly effective birth control method during the study and through 30 days after the last dose of study medication
• Male subjects must agree to use condoms to prevent potential fetal or partner exposure through seminal fluid, in addition to the use of highly effective pregnancy prevention measures with female partners of childbearing potential during the study and through 30 days after the last dose of study medication
• Subjects must agree to not donate ova or sperm through 30 days after the last dose of study medication
• Able to understand the correct technique for the use of the nebulizer device(s) at Screening, Day -1, and prior to dosing on Day 1, as applicable
• Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol
• Part B Only: Willing to undergo 2 bronchoscopy procedures and must be able to tolerate the bronchoscopy at Screening
• Part C (Subjects with IPF):
• Male subjects ≥ 45 years and female subjects ≥ 55 years at Screening

You may not qualify if:

• Parts A and B:
• History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator or designee
• Abnormal ECG measurements at Screening (any of the three individual ECG measurements) or prior to dosing indicating a second- or third- degree atrioventricular block, or one or more of the following:
• QRS \> 120 msec
• QTcF \> 450 msec (males) or \> 460 msec (females)
• PR interval \> 220 msec
• Known personal or family history of congenital long QT syndrome or known family history of sudden death.
• Supine resting bradycardia (pulse \< 40 beats per minute \[bpm\]) or a supine resting tachycardia (pulse \> 100 bpm) at Screening or prior to dosing on Day 1.
• Abnormal renal function as defined by estimated glomerular filtration rate (eGFR) \<90mL/min/1.73m\^2 at Screening
• History of clinically significant hypotensive episodes or symptoms of fainting, dizziness, or light-headedness.
• History or symptoms of clinically relevant neurologic disease, including transient ischemic attack, stroke, seizure disorder, or behavioral disturbances.
• History of lymphoma, leukemia, or other types of malignancy (except for completely resected squamous or basal cell cancer).
• Any signs of respiratory tract infection within 6 weeks of Screening that is deemed clinically significant by the Investigator and Sponsor's Medical Monitor.
• Has a current bacterial, parasitic, fungal, or viral infection; any infection requiring hospitalization or intravenous antibiotics within 6 months prior to Screening; any non respiratory tract infection requiring oral or topical antimicrobial treatment within 2 weeks prior to Screening; a history of more than one episode of herpes zoster infection.
• Subject has any condition of the oro-laryngeal or respiratory tract (including, but not limited to, prior surgery) that could possibly affect drug administration, deposition, or absorption, or ability to perform lung function measurements (spirometry), as determined by the Investigator or Sponsor.

Sponsors & Collaborators

• Theravance Biopharma: lead

Study Sites (1)

Theravance Biopharma Investigational Site

Manchester, M23 9QZ, United Kingdom

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Pulmonary Fibrosis; Fibrosis; Lung Diseases, Interstitial

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Medical Monitor

  Theravance Biopharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Double-Blinded, Placebo-Controlled

Study Record Dates

• First Submitted: October 8, 2020
• First Posted: October 19, 2020
• Study Start: October 15, 2020
• Primary Completion: May 6, 2021
• Study Completion: October 4, 2021
• Last Updated: February 23, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)