A Study to Evaluate Safety, Tolerability and Pharmacokinetics of RSN0402 in Healthy Volunteers

NCT06482190 | Recruiting Phase 1 DMC

• 1 other identifier: RES-RSN0402-P1
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 3

Brief Summary

This is a phase 1, randomized, First in Human (FIH), double-blinded, placebo-controlled study to assess the safety, tolerability, and PK of RSN0402 in healthy volunteers. A total of about 72 participants are expected to be enrolled.

Conditions

Idiopathic Pulmonary Fibrosis; Lung; Disease, Interstitial, With Fibrosis

Keywords

Respiratory system

Outcome Measures

Primary Outcomes (6)

• Number of participants with Treatment emergent Adverse events (TEAEs)

  TEASs will be collected to assess participant's safety after RSN0402 administration in both Single ascending dose (SAD) and multiple ascending dose (MAD).

  SAD - From Screening to Day 14 (end of study); MAD - From Screening to Day 13 (end of study)

• Number of participants with changes in physical examination

  Full physical examination will comprise a routine medical examination including examination of head, eyes, ears, nose, throat and neck, abdomen, the respiratory system, central and peripheral nervous system, cardiovascular system, gastrointestinal system including mouth, musculoskeletal system, and skin. Brief physical examination will include at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen).

  SAD- From Screening to Day 14 (end of study) post dose; MAD - At screening, Day -2, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9 and Day 13 (end of study) post dose.

• Number of participants with changes in serum blood parameters

  Serum blood parameters include hematology, biochemistry, coagulation

  SAD- At Screening, Day -2, Day 3, Day 7, Day 10 and Day 14 (end of study) post dose; MAD- At Screening, Day -2, Day 3, Day 6, Day 9 and Day 13 (end of study) post dose.

• Number of participants with changes in Urine parameters

  Urine cotinine test and urine pregnancy test will be assessed

  SAD: Urine pregnancy test will be conducted on Day -2 and Day 7 and Urine cotinine test in screening, Day -2 and Day 7 post first dose. MAD: Urine pregnancy test will be conducted on Day -2, Urine cotinine test in screening and Day -2.

• Number of participants with changes in vital signs

  Heart rate, systolic/diastolic blood pressure, respiratory rate, oxygen saturation, and temperature

  SAD- At Screening, Day-2, Day 1, Day 2, Day 3, Day 7, Day 8, Day 9, Day 10 and Day 14 (end of study) post dose; MAD - At screening, Day - 2, Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9 and Day 13 (end of study) post dose.

• Number of participants with change in Absolute Forced Expiratory Volume in 1 second (FEV1) >10%

  Spirometry will be conducted in accordance with ATS and ERS guidelines

  SAD- At Screening, Day -2, Day 1, Day 2, Day 3, Day 7, Day 8, Day 9, Day 10 and Day 14 (end of study) post dose; MAD - At screening, Day- 2, Day 1, Day 3, Day 6, Day 9 and Day 13 (end of study) post dose.

Secondary Outcomes (13)

• Changes in AUC 0-inf (Area under curve from time 0 to infinity) of RSN0402 with 5 different doses of SAD.PK samples are collected at total of 17 time points from pre-dose and up to 48 hours after dosing on Day 3.

  SAD-Day 1, Day 2, Day 3, Day 8, Day 9 and Day 10 post first dose; MAD- Day 1 to Day 9 post dose

• PK parameter: Changes in AUC 0-t (Area under curve from time 0 to last measurable concentration) of RSN0402.

  SAD-Day 1, Day 2, Day 3, Day 8, Day 9 and Day 10; MAD- Day 1 to Day 9 post dose

• PK parameter: Changes in Cmax (Maximum observed plasma concentration) of RSN0402

  SAD-Day 1, Day 2, Day 3, Day 8, Day 9 and Day 10; MAD- Day 1 to Day 9 post dose

• PK parameter: Changes in Tmax (Time to Maximum) of RSN0402

  SAD-Day 1, Day 2, Day 3, Day 8, Day 9 and Day 10; MAD- Day 1 to Day 9 post dose

• PK parameter: Changes in t1/2 (Apparent terminal elimination half-life) of RSN0402

  SAD-Day 1, Day 2, Day 3, Day 8, Day 9 and Day 10; MAD- Day 1 to Day 9 post dose

Study Arms (3)

RSN0402 Part 1

EXPERIMENTAL

Part 1 is SAD with 5 cohorts (1 to 5) where each participant will receive single dose of RSN0402 powder for inhalation or placebo following a 10hour fast. Cohort 2 will also receive single dose of nintedanib oral soft capsule.

Drug: RSN0402 Part 1

RSN0402 Part 2

EXPERIMENTAL

Part 2 is MAD with 4 cohorts (6 to 9) where each participant will receive multiple doses powder for inhalation or placebo following a 10 hr fast.

Drug: RSN0402 Part 2

Placebo

PLACEBO COMPARATOR

Matching doses of placebo

Drug: Placebo

Interventions

RSN0402 Part 1 DRUG

Participants will receive single ascending doses of 2mg, 4mg, 8mg, 12 mg, and 16mg of RSN0402 or placebo on Day 1 for Cohort 1 to 5. Cohort 2(4mg) will also a single dose of 150 mg nintedanib soft capsule will be administered orally after at least 7-days washout period.

RSN0402 Part 1

RSN0402 Part 2 DRUG

Participants will receive multiple ascending doses of 4mg ,8mg,12mg ,16mg of RSN0402 or placebo administered once daily from Day 1 to Day 7 for Cohort 6 to 9.

RSN0402 Part 2

Placebo DRUG

Participants will receive matching placebo across Part 1 and Part 2 of the study.

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant is overtly healthy or has no clinically significant condition as determined by PI/Sub-Investigator including medical history, vital signs, ECG, laboratory tests, and physical examination at Screening and admission (Day -2 and Day -1).
• Participant has normal lung function assessment with FEV1 of at least 80% of the predicted value and FEV1/FVC ratio of \> 0.7 measured at Screening.
• Availability to participate voluntarily for the entire study duration and willing to adhere to all protocol requirements.
• Participant must be 18 to 60 years of age inclusive, at the time of signing the informed consent.
• Male participant with body weight of ≥ 50.0 kg, female participant with body weight ≥ 45.0 kg; males or females with body mass index (BMI) of ≥ 18 to \< 30.0 kg/m² at screening.
• Female participants of childbearing potential must have a negative serum pregnancy test result at Screening and a negative pregnancy test result at Baseline and agree to use acceptable methods of contraception as per protocol.
• Male participants agree to use acceptable methods of contraception if the male participant's partner could become pregnant from the time of signing the informed consent until 3 months after EOS/ET.

You may not qualify if:

• Vulnerable participants (ie, people under any administrative or legal supervision).
• Clinical laboratory evidence or clinical diagnosis of human immunodeficiency virus (HIV) infection, hepatitis C virus (HCV) infection, or chronic hepatitis B virus (HBV) infection (as shown by hepatitis B surface antigen \[HbsAg\] positivity).
• Evidence of a clinically significant cardiovascular, renal, hepatic, hematological, gastrointestinal (GI), pulmonary, metabolic-endocrine, neurological, or psychiatric disease or psychiatric disease within the previous 2 years; or evidence of active airway infection.
• Known hypersensitivity to the active substance(s) of the drug or its excipient (lactose monohydrate, which contains small amounts of milk protein) and/or intolerance with lactose.
• History of vasovagal syncope in past 5 years.
• History of anaphylactic/anaphylactoid reactions.
• History of seizures including febrile seizures.
• History of bleeding disorders or currently being treated with anticoagulants or regular using aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs).
• History of thrombotic event (including stroke and transient ischemic attack) within 6 months prior to Screening.
• History of pulmonary arterial hypertension.
• Cardiovascular diseases, any of the following: Severe hypertension (uncontrolled under treatment ≥ 160/100 mmHg at multiple occasions) within 3 months prior to Screening; history of myocardial infarction; history of unstable cardiac angina
• Surgery of the GI tract (except appendectomy or simple hernia repair).
• Any condition requiring regular concomitant treatment (including vitamins, recreational drugs, and dietary or herbal products) or likely to need any concomitant treatment during the study. As an exception, paracetamol and ibuprofen for occasional pain will be allowed.
• Intake of any medication that could affect the outcome of the study. As an exception, contraceptives and hormone replacement therapy are allowed. The use of medicines that are potential CYP3A4 inducers or inhibitors will be restricted for at least 2 weeks prior to the first dose of the IP and during the study.
• Use of any prescription drugs or the medication leading to prolong the QT/QTc interval within 14 days or 7 half-lives (whichever is longer) prior to dosing; over the-counter (OTC) medication, supplements, or vitamins within 7 days or 7 half lives (whichever is longer) prior to the first dose of the IP.

Sponsors & Collaborators

• Shenzhen Resproly Biopharmaceutical Co., Ltd: lead
• Resproly Australia Pty Ltd: collaborator

Study Sites (3)

Nucleus Network Pty Ltd

Geelong, Victoria, 3220, Australia

RECRUITING

Nucleus Network

Melbourne, Victoria, 3004, Australia

RECRUITING

Nucleus Network Pty Ltd

Melbourne, 3004, Australia

RECRUITING

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Disease

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Yiqing Cui

CONTACT

+86 13383111601; yiqing.cui@novotech-cro.com

Shugui He

CONTACT

+86 17722668796; shuguihe@resproly.com

Study Design

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

Study Record Dates

• First Submitted: June 25, 2024
• First Posted: July 1, 2024
• Study Start: July 11, 2024
• Primary Completion: December 27, 2024
• Study Completion: February 10, 2025
• Last Updated: July 8, 2024

Record last verified: 2024-06

Locations

AU (3)