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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05914909




Registration number
NCT05914909
Ethics application status
Date submitted
28/05/2023
Date registered
22/06/2023
Date last updated
13/02/2024

Titles & IDs
Public title
Safety, Tolerability, PK and PD Study of AD-214 Administered to Healthy Volunteers and Patients With Interstitial Lung Disease or Chronic Kidney Disease
Scientific title
A Phase 1, Randomised, Placebo-controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of 10 mg/kg AD-214 When Administered Intravenously to Healthy Volunteers and Patients With Interstitial Lung Disease or Chronic Kidney Disease
Secondary ID [1] 0 0
1AD-AD-214-2301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Interstitial Lung Disease 0 0
Chronic Kidney Diseases 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - AD-214
Other interventions - Placebo

Experimental: Part A: AD-214 in Healthy Volunteers -

Placebo Comparator: Part A: Placebo in Healthy Volunteers -

Experimental: Part B: AD-214 in patients with ILD or CKD -

Placebo Comparator: Part B: Placebo in patients with ILD or CKD -


Other interventions: AD-214
AD-214 is a recombinant Fc-fusion protein that selectively binds to CXCR4 to antagonise the SDF-1/CXCR4 axis.

Other interventions: Placebo
Placebo
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of adverse events that are related to treatment in healthy volunteers [Safety and Tolerability]
Timepoint [1] 0 0
141 days
Primary outcome [2] 0 0
Incidence of adverse events that are related to treatment in patients with ILD or CKD [Safety and Tolerability]
Timepoint [2] 0 0
57 days

Eligibility
Key inclusion criteria
- All Study Parts:

1. Male or female aged = 18 to = 65 years of age at the time of consent.

2. Provision of signed informed consent prior to study entry and agreement to adhere
to all study protocol requirements.

3. Agreement to adhere to the current state and national advice regarding minimising
exposure to corona virus disease from the first screening visit until the EoS
visit.

4. Maximum weight of 100.00 kg and BMI > 18.0 and < 30.0 kg/m2 (inclusive) at the
time of consent. Participants must also be < 100.00 kg at Day -1.

5. Normal vital signs after = 5 minutes resting supine position:

- > 90 mmHg and <160 mmHg SBP

- 50 mmHg and < 95 mmHg DBP

- > 45 bpm and < 101 bpm HR

- Body temperature >35.5oC and =37.6°C

6. Ability and willingness to attend the necessary visits to the CRU.

7. Have established use of highly effective, double barrier contraception (both
partners) prior to screening, during the study AND for 90 days following
completion of dosing as specified below in this criterion.

Double barrier contraception is defined as a condom AND 1 other form of the
following:

- Hormonal and non-hormonal forms of contraception (including oral, depot or
injectable)

- IUD/IUS

- Sterilised male partner. Rhythm methods will not be considered as highly
effective methods of birth control.

Participant abstinence from heterosexual sexual activity, if their usual and
preferred lifestyle, for the duration of the study and for 90 days after the last
dose of AD-214 is acceptable.

Participants who are in a same sex relationship will not require contraception
unless they enter into a heterosexual relationship.

Female participants and female partners of male participants must use double
barrier contraception including condom from start of study and for 90 days after
last dose of AD-214.

8. Male participants must refrain from sperm donation and female participants must
refrain from ova donation from the first dose of AD-214 and for 90 days after
last dose of AD-214.

9. WOCBP must have a negative serum pregnancy test at Screening and a negative urine
pregnancy test on Day -1. Females not of childbearing potential must be
surgically sterile or post-menopausal (defined as cessation of regular menstrual
periods for at least 12 months), confirmed by FSH level at Screening.

10. Must not regularly consume more than 10 standard alcoholic drinks in a week and
more than 4 standard alcoholic drinks in any one day for the duration of the
study, AND must for the duration of the study agree to:

- abstain from alcohol intake from 48 hours before each study drug
administration through to discharge from the CRU AND

- abstain from alcohol intake from 24 hours before each outpatient study
visit.

11. Must not be a regular smoker of > 5 cigarettes/e-cigarettes/cigars/pipes a day
AND must, for the duration of the study, agree to:

- smoke no more than 5 cigarettes/ e-cigarettes/cigars/pipes in any 1 day from
48 hours before first study drug administration until the EoS visit

- abstain from smoking 24 hours before each study drug administration through
to discharge from the CRU

- abstain from smoking from 24 hours before each outpatient study visit.

Part A: HVs only

12. Must be in good general health, in the opinion of the Investigator, with no
significant medical history, have no clinically significant abnormalities on
physical examination at Screening, and/or before administration of the initial
dose of study drug.

13. Must have clinical laboratory values within normal range in the opinion of the
Investigator. Repeat screening may be permitted if out of range values are deemed
NCS by the Investigator. Exercise induced elevated creatinine kinase levels may
be permitted if out of range values are deemed NCS by the Investigator.

Part B: Patients with ILD or CKD

14. Clinical and radiological features that are consistent with an established
diagnosis of any of the following diseases in which high expression of CXCR4 has
been implicated ;

- CKD due to LN, DN, and FSGS OR

- IPF OR fibrotic ILD associated with any of the following: CVD, Fibrotic
non-specific interstitial pneumonia (fNSIP), Chronic fibrosing
hypersensitivity pneumonitis (cHP)

15. Must be on a stable regimen of systemic medications for their ILD or CKD and
expected to continue on this regimen until completion of the final EoS visit.

Patients with ILD:

16. Most recent HRCT image (taken within 12 months of Screening) showing either UIP
pattern as per current ATS/ ERS/ JRS/ALAT guidelines in IPF patients, OR, for
patients with fibrotic ILD, a > 10% extent of fibrosing lung disease.

17. Predicted FVC = 50% on PFTs conducted within 3 months of Screening.

18. Predicted haemoglobin-corrected DLCO = 25% in PFTs conducted within 6 months of
Screening.

Patients with CKD:

19. Estimated glomerular filtration rate greater than or equal to 30 mL/min/1.73 m2

20. Proteinuria = 1 based on absolute amount in grams per day (g/d) as measured in 1
complete and valid 24-hour urine collection during Screening.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- All Study Parts:

1. Previously received AD-214

2. Received any IMP within 30 days or 5 half-lives prior to Screening, whichever is
longer.

3. Received an investigational vaccine, recombinant protein or monoclonal antibody
within 6 months, a live attenuated registered vaccine within 60 days, or a
registered vaccine within 30 days prior to the first dose of the IP.

4. Received blood or blood products within 1 month prior to Screening.

5. Blood donation or significant blood loss (> 280 mL) within 60 days prior to the
first dose of the IP.

6. Plasma donation within 7 days prior to the first dose of the IP.

7. A bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy,
or platelet disorder requiring special precautions) or significant bruising or
bleeding difficulties with blood draws.

8. Unable to provide a blood sample without undue trauma or distress or inadequate
venous access.

9. Recent (less than 6 weeks) significant wound (in the opinion of the PI), or
presence of an ongoing non-healing skin wound on Day -1.

10. Positive test for HIV, HBsAg, or anti-HCV at Screening.

11. A psychiatric condition that precludes compliance with the protocol in the
opinion of the Investigator; past or present psychoses; past or present bipolar
disorder; disorder requiring lithium; or within 5 years prior to Screening, a
history of suicide plan.

12. Clinical signs of active infection and/or a temperature of > 37.7°C at the time
of Screening. Study entry may be deferred at the discretion of the PI.

13. Fever in the past 7 days within Screening or Day 1 AND symptoms reflective of an
active respiratory tract infection (in the opinion of the Investigator).

14. QTcF > 450 msec for females and > 470 msec for males, or QTcF > 480 msec in
participants with Bundle Branch Block.

15. Active malignancy and/or history of malignancy in the past 5 years, with the
exception of non-melanoma skin cancer, or low grade cervical intraepithelial
neoplasia.

16. A history of severe allergic, anaphylactic, or other hypersensitive reactions to
AD-214 excipients, a history of drug or other allergy including severe allergic
reaction that in the opinion of the Investigator or Sponsor MM contraindicates
their participation.

17. Surgery within the past 3 months prior to the first study drug administration
determined by the PI to be clinically relevant.

18. History or presence of alcohol abuse (defined as an average weekly intake of > 10
units. One unit is equivalent to 10 g of alcohol and the following can be used as
a guide: a half-pint [~240 mL] of beer, 1 glass [125 mL] of wine or 1 [30 mL]
measure of spirits) or drug abuse (including recreational marijuana use) within
the 2 years prior to the first study drug administration, and unwillingness to be
totally abstinent during the dosing period.

19. Positive alcohol breath test or urine drugs of abuse screen at Screening or Day
-1

20. Inability to adhere to smoking and alcohol restrictions for the duration of the
study.

21. Pregnant or lactating.

Part A: HVs:

22. Any clinically significant abnormality at Screening determined by medical
history, physical examination, biochemistry, haematology, coagulation,
urinalysis, and 12-lead ECG.

23. History of recurrent infections, with the exception of urinary tract infections.

24. Serious (as per the discretion of the PI or Investigator) local infection or
systemic infection requiring antibiotic or anti-viral treatment within 3 months
from Screening.

25. Extensive chronic obstructive pulmonary disease including emphysema and chronic
bronchitis as judged by the PI or Investigator.

26. A history of or current chronic medical condition (eg, hypertension, asthma,
diabetes, or cardiac disease) or any other medical, social, or psychiatric
condition, significant co-morbidities, or any finding during Screening, 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.

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

28. Any acute illness within 30 days prior to Day 1.

Part B:

All Patients

29. Alanine aminotransferase (ALT) > 2 × ULN and total bilirubin > 1.5 × ULN.

30. Use of anticoagulants or antiplatelet agents (excluding aspirin).

31. Severe/significant arterial hypertension, heart failure or coronary heart
disease.

32. Significant hypoxia, requiring > 2 L/min oxygen chronically to maintain a resting
oxygen saturation > 89%.

Patients with ILD

33. Poor exercise tolerance with 6MWD < 150 metres.

34. Extensive emphysema on HRCT as defined by being greater in extent than the
accompanying fibrotic lung disease.

35. Evidence of physiologically significant obstructive airways disease as evident
from

- FEV1/FVC ratio < 0.7 OR

- Bronchodilator response defined by an increase of = 12% and an increase of =
200 mL in the FEV1 after bronchodilator

36. Other explanation for lung fibrosis, including but not limited to radiation,
sarcoidosis, bronchiolitis obliterans organising pneumonia, HIV, viral hepatitis.

Patients with CKD

37. Post-transplant patients

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/07/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/02/2024
Sample size
Target
Accrual to date
Final
8
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AdAlta Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase I, double-blind, placebo-controlled study to evaluate the safety,
tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of a 10 mg/kg
dose of AD-214 when administered to healthy volunteers (HVs) (Part A) or patients with
interstitial lung disease (ILD) or chronic kidney disease (CKD) (Part B). The study will be
performed in Australia at up to two clinical sites.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05914909
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Emir Redzepagic, Dr
Address 0 0
CMAX Clinical Research Pty Ltd
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries