Phase 1 Safety, Tolerability, PK & PD Study of AD-214 Administered to Healthy Volunteers and Patients With ILD

• ClinicalTrials.gov Identifier: NCT04415671
• Recruitment Status: Recruiting
• First Posted: June 4, 2020
• Last Update Posted: November 6, 2020
• Sponsor: AdAlta Limited
• Information provided by (Responsible Party): AdAlta Limited

Study Description

Brief Summary:

This is a first in human (FIH), multi-center, dose escalating study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of AD-214 when administered to healthy volunteers (HVs) and to patients with Interstitial Lung Disease (ILD). The study in HVs will be single ascending dose (SAD), randomized, double blind, and placebo-controlled (Part A). The study in ILD patients will be open-label, SAD (Part B), and multiple ascending dose (MAD) (Part C).

Condition or disease	Intervention/treatment	Phase
Interstitial Lung Disease	Biological: AD-214; Other: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 98 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: SAD Part A in HVs- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) SAD Part B in ILD patients- None (Open Label) SAD Part C in ILD patients - None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Dose-escalating Study of the Safety, Tolerability, and Pharmacokinetics of Single and Repeat Doses of AD-214 When Administered Intravenously to Healthy Volunteers and to Patients With Interstitial Lung Disease
• Actual Study Start Date: June 19, 2020
• Estimated Primary Completion Date: July 31, 2022
• Estimated Study Completion Date: July 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part A- AD-214 SAD in Healthy Volunteers	Biological: AD-214; AD-214 is a recombinant Fc-fusion protein that selectively binds to CXCR4 to antagonise the SDF-1/CXCR4 axis.
Placebo Comparator: Part A-Placebo SAD in Healthy Volunteers	Other: Placebo; Placebo
Experimental: Part B- AD-214 SAD in patients with ILD	Biological: AD-214; AD-214 is a recombinant Fc-fusion protein that selectively binds to CXCR4 to antagonise the SDF-1/CXCR4 axis.
Experimental: Part C-AD-214 MAD in patients with ILD	Biological: AD-214; AD-214 is a recombinant Fc-fusion protein that selectively binds to CXCR4 to antagonise the SDF-1/CXCR4 axis.

Outcome Measures

Primary Outcome Measures :

1. Safety and Tolerability as assessed by the number of abnormal laboratory values and/or adverse events that are related to treatment [ Time Frame: SAD Part A & B - 28 days. MAD Part C - 50 days ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

All Study Parts:

1. Must provide signed informed consent prior to study entry and agree to adhere to all study protocol requirements.
2. Maximum weight of 100 kg at the time of consent and body mass index (BMI) >18 and < 30 kg/m2 (inclusive)
3. Must agree to abstain from alcohol intake from 48 hours before first study drug administration through to final study visit
4. Must agree to abstain from smoking from 48 hours before first study drug administration through to final study visit
5. Must have a negative urine drug screen and cotinine test, and alcohol breath test at Screening and on Day -1 (admission).
6. Must agree to use highly effective, double barrier contraception (both male and female partners) at least 30 days prior to dosing on day 1, during the study AND for 90 days following completion of dosing
7. Male participants must refrain from sperm donation from start of study and for 90 days after last dose of AD-214

8. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1.

   Part A (SAD) in Healthy Volunteers:

9. Participants must be in good general health, with no significant medical history, and no clinically significant abnormalities on physical examination at Screening, and/or before administration of the initial dose of study drug.

10. Participants must have clinical laboratory values within normal range or < 1.5 x upper limit of normal (ULN) as specified by the testing laboratory at Screening.

    Part B (SAD) and Part C (MAD) (Interstitial Lung Disease):

11. Patients with clinical and radiological features that in the opinion of the PI are consistent with a diagnosis of fibrotic ILD associated with idiopathic pulmonary fibrosis (IPF), Collagen-vascular disease (CVD), Fibrotic non-specific interstitial pneumonia (fNSIP) or Chronic fibrosing hypersensitivity pneumonitis (cHP).
12. Predicted forced vital capacity (FVC) ≥ 50% on pulmonary function tests (PFTs) conducted within 3 months of Screening.
13. Predicted haemoglobin-corrected diffusing capacity of the lung for carbon monoxide (DLCO) ≥ 25% in PFTs conducted within 6 months of Screening.

Exclusion Criteria:

All Study Parts:

1. Received any Investigational Medicinal Product (IMP) within 30 days (4 months if the previous drug was a new chemical entity) or 5 half-lives prior to Screening
2. Received an investigational vaccine within 6 months, a live attenuated vaccine within 60 days or a registered vaccine within 30 days prior to the first dose of the investigational product.
3. Received blood products within 1 month prior to Screening.
4. Blood donation or significant blood loss (> 450 mL) within 60 days prior to the first administration of investigational product
5. Plasma donation within 7 days prior to the first administration of investigational product.
6. A bleeding disorder diagnosed by a doctor or significant bruising or bleeding difficulties with blood draws.
7. Known history of Human Immunodeficiency Virus (HIV) or HIV antibody positive.
8. Hepatitis B surface Antigen (HBsAg) positive or Hepatitis B Virus (HBV) polymerase chain reaction (PCR) positivity. Hepatitis C Virus (HCV) antibody positive or HCV PCR positivity.
9. Any clinically significant abnormality at Screening determined by medical history, physical examination, blood chemistry, hematology, coagulation, urinalysis and 12-lead electrocardiogram (ECG).
10. A history of or current clinically significant gastrointestinal, hepatic, renal, cardiovascular, respiratory (apart from ILD), endocrine, oncological, immunodeficiency, neurological, metabolic, hematological, autoimmune or social or psychiatric condition which in the investigator's opinion may interfere with the study objectives, may put the participant at risk or may make the participant unsuitable for participation in the study.
11. Surgery within the past 3 months prior to the first study drug administration determined by the PI to be clinically relevant.
12. History or presence of alcohol or drug abuse

13. Females who are pregnant or lactating.

    Part A (SAD) in Healthy Volunteers:

14. Use of any prescription or over the counter medication (with the exception of paracetamol and contraceptives) within 7 days of first study drug administration.

    Part B (SAD) and Part C (MAD) in Patients with Interstitial Lung Disease:

15. Received nintedanib or pirfenidone or other systemic medications for their ILD within 30 days of Day -1. Ongoing use of systemic corticosteroids (prednisolone or equivalent) at a dose of ≤ 10 mg/day is permitted.
16. Evidence of significant deterioration in pulmonary function in the preceding 30 days at Screening and on Day -1.
17. Significant hypoxia, requiring >2 L/min oxygen chronically to maintain a resting oxygen saturation >89% (at Screening).
18. Poor exercise tolerance with 6 Minute Walking Distance (6MWD) < 150 m (at Screening).
19. Extensive emphysema on HRCT as defined by being greater in extent than the accompanying fibrotic lung disease.
20. Evidence of physiologically significant obstructive airways disease
21. Other explanation for lung fibrosis, including but not limited to radiation, sarcoidosis, bronchiolitis obliterans organizing pneumonia.
22. Alanine transferase (ALT) >2 x ULN OR total bilirubin >1.5 x ULN at screening.
23. Use of anticoagulants or antiplatelet agents (excluding aspirin) at Screening and Day -1.

Contacts and Locations

Contacts

Contact: Claudia C Gregorio-King, PhD; +61 3 9479 5159; clinical@adalta.com.au

Locations

Australia, New South Wales

Scientia Clinical Research Ltd; Not yet recruiting

Randwick, New South Wales, Australia, 2031

Contact: Puja Motwani +61 02 9382 5820 puja.motwani@scientiaclinicalresearch.com.au

Principal Investigator: Charlotte Lemech, Dr

Australia, South Australia

CMAX Clinical Research Pty Ltd; Recruiting

Adelaide, South Australia, Australia, 5000

Contact: Dianne Pepper +61 8 7088 7939 dianne.pepper@cmax.com.au

Principal Investigator: Sepehr Shakib, Dr

Sponsors and Collaborators

AdAlta Limited

More Information

• Responsible Party: AdAlta Limited
• ClinicalTrials.gov Identifier: NCT04415671
• Other Study ID Numbers: ADA-AD-214-1A
• First Posted: June 4, 2020
• Last Update Posted: November 6, 2020
• Last Verified: July 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Interstitial; Respiratory Tract Diseases