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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/NCT05876312




Registration number
NCT05876312
Ethics application status
Date submitted
17/05/2023
Date registered
25/05/2023
Date last updated
18/11/2023

Titles & IDs
Public title
Safety, Tolerability, PK and PD of ADX-038 in HV and Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients
Scientific title
A Phase 1, Randomized, Placebo-Controlled, Double Blind Single Ascending Dose Study in Healthy Volunteers Followed by Open Label Treatment in Patients With PNH to Evaluate the Safety, Tolerability, PK and PD of ADX-038
Secondary ID [1] 0 0
ADX-038-101
Universal Trial Number (UTN)
Trial acronym
PNH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paroxysmal Nocturnal Hemoglobinuria (PNH) 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ADX-038
Treatment: Drugs - Placebo

Experimental: PART A - Active ADX-038 administered to HV - For each cohort in Part A (SAD), 8 participants will be randomized in a 3:1 ratio; 6 participants to active (ADX-038): 2 participants to control (matched placebo). Randomization will be on Day 1. Initially, 2 sentinel participants (1 active and 1 placebo) will be randomized and dosed. The sentinel participants will be evaluated for safety. The investigator's assessment and the independent medical monitor will decide upon the randomization and dosing of the 6 remaining participants (5 active and 1 placebo) according to the randomization schedule.

Placebo Comparator: PART A- Placebo administered to HV - For each cohort in Part A (SAD), 8 participants will be randomized in a 3:1 ratio; 6 participants to active (ADX-038): 2 participants to control (matched placebo). Randomization will be on Day 1. Initially, 2 sentinel participants (1 active and 1 placebo) will be randomized and dosed. The sentinel participants will be evaluated for safety. The investigator's assessment and the independent medical monitor will decide upon the randomization and dosing of the 6 remaining participants (5 active and 1 placebo) according to the randomization schedule.

Experimental: PART B - ADX-038 administered to PNH participants - This will be initiated at the dose level determined by the Safety Review Committee from SAD in HVs. The treatment of HAE participants is an open-label study.


Treatment: Drugs: ADX-038
siRNA duplex oligonucleotide

Treatment: Drugs: Placebo
Saline
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety in Healthy Volunteers
Timepoint [1] 0 0
365 days
Primary outcome [2] 0 0
Safety in Healthy Volunteers
Timepoint [2] 0 0
365 days
Primary outcome [3] 0 0
Safety in Paroxysmal Nocturnal Hemoglobinuria
Timepoint [3] 0 0
365 days
Primary outcome [4] 0 0
Safety in Paroxysmal Nocturnal Hemoglobinuria
Timepoint [4] 0 0
365 days
Secondary outcome [1] 0 0
Pharmacokinetics in Healthy Volunteers
Timepoint [1] 0 0
8 days
Secondary outcome [2] 0 0
Pharmacokinetics in Paroxysmal Nocturnal Hemoglobinuria
Timepoint [2] 0 0
8 days
Secondary outcome [3] 0 0
Pharmacokinetics in Healthy Volunteers
Timepoint [3] 0 0
8 days
Secondary outcome [4] 0 0
Pharmacokinetics in Paroxysmal Nocturnal Hemoglobinuria
Timepoint [4] 0 0
8 days
Secondary outcome [5] 0 0
Pharmacokinetics in Healthy Volunteers
Timepoint [5] 0 0
8 days
Secondary outcome [6] 0 0
Pharmacokinetics in Paroxysmal Nocturnal Hemoglobinuria
Timepoint [6] 0 0
8 days
Secondary outcome [7] 0 0
Pharmacokinetics in Healthy Volunteers
Timepoint [7] 0 0
8 days
Secondary outcome [8] 0 0
Pharmacokinetics in Paroxysmal Nocturnal Hemoglobinuria
Timepoint [8] 0 0
8 days
Secondary outcome [9] 0 0
Pharmacokinetics in Healthy Volunteers
Timepoint [9] 0 0
8 days
Secondary outcome [10] 0 0
Pharmacokinetics in Paroxysmal Nocturnal Hemoglobinuria
Timepoint [10] 0 0
8 days
Secondary outcome [11] 0 0
Pharmacokinetics in Healthy Volunteers
Timepoint [11] 0 0
8 days
Secondary outcome [12] 0 0
Pharmacokinetics in Paroxysmal Nocturnal Hemoglobinuria
Timepoint [12] 0 0
8 days
Secondary outcome [13] 0 0
Pharmacokinetics in Healthy Volunteers
Timepoint [13] 0 0
8 days
Secondary outcome [14] 0 0
Pharmacokinetics in Paroxysmal Nocturnal Hemoglobinuria
Timepoint [14] 0 0
8 days
Secondary outcome [15] 0 0
Pharmacokinetics in Healthy Volunteers
Timepoint [15] 0 0
8 days
Secondary outcome [16] 0 0
Pharmacokinetics in Paroxysmal Nocturnal Hemoglobinuria
Timepoint [16] 0 0
8 days
Secondary outcome [17] 0 0
Pharmacodynamics in Healthy Volunteers
Timepoint [17] 0 0
365 days
Secondary outcome [18] 0 0
Pharmacodynamics in Paroxysmal Nocturnal Hemoglobinuria
Timepoint [18] 0 0
365 days
Secondary outcome [19] 0 0
Pharmacodynamics in Healthy Volunteers
Timepoint [19] 0 0
365 days
Secondary outcome [20] 0 0
Pharmacodynamics in Paroxysmal Nocturnal Hemoglobinuria
Timepoint [20] 0 0
365 days
Secondary outcome [21] 0 0
Pharmacodynamics in Paroxysmal Nocturnal Hemoglobinuria
Timepoint [21] 0 0
365 days
Secondary outcome [22] 0 0
Pharmacodynamics in Paroxysmal Nocturnal Hemoglobinuria
Timepoint [22] 0 0
365 days

Eligibility
Key inclusion criteria
Inclusion Criteria

1. Male and female adults 18 to 65 years old 2. Serum LDH levels are at least 1.25-fold
above the ULN at screening 3. Mean hemoglobin (Hb) <12 g/dL 4. A history of red blood cell
(RBC) transfusion due to PNH within at least 3 months of screening 5. Body mass index (BMI)
between 18 and 30 kg/m2 3. Contraception use by men or women should be consistent with
local regulations regarding the methods of contraception for those participating in
clinical studies 4. Willing and able to provide informed consent and comply with all study
visits and procedures 5. Neisseria meningitis vaccination 6. Pneumococcus vaccination 7.
Hemophilus influenzae vaccination
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria

1. Known or suspected hereditary or acquired complement deficiency

2. History of clinically significant arterial or venous thrombosis, or current history of
a clinically significant prothrombotic risk

3. History of hematopoietic stem cell transplantation

4. History of meningococcal infection

5. Any significant medical history

6. Active malignancy and/or history of malignancy in the past 5 years

7. Any active viral, bacterial, parasitic, or fungal infection or acute illness,
inclusive of cold/flu, herpes zoster, or COVID-19, within 30 days prior to the first
study drug administration

8. Any evidence of sero-positive autoimmune connective tissue diseases

9. Any evidence of active inflammatory conditions (including inflammatory bowel disease
or cryoglobulinemia)

10. History of previous or current tuberculosis infection

11. Prior splenectomy

12. Major surgery or significant traumatic injury occurring within 3 months prior to
signature of the PICF.

13. Have any other conditions that, in the opinion of the Investigator or Sponsor, would
make the participant unsuitable for inclusion

14. Liver impairment, history of liver disease, Gilbert's syndrome, or abnormal liver
function tests at screening and/or admission.

19. Positive serology tests for human immunodeficiency virus hepatitis B surface antigen or
hepatitis C virus 20. Use of any prescription, vaccines, supplements/vitamins, or over-the
counter medication 21. Treatment with another investigational product within 30 days 22.
Known any clinically significant allergic reactions 23. Known hypersensitivity to any of
the study drug ingredients or penicillin. 24. History or presence of alcohol 25. Blood
donation 26. Pregnancy 27. May have a higher risk to be exposed to infected individuals,
for example active healthcare employees.

Criteria (Part B) Inclusion Criteria 28. Male and female adults 18-65 years old 29.
Confirmed diagnosis of PNH based on documented clone size of PNH blood cells by flow
cytometry.

30. Serum LDH levels are at least 1.25-fold above the ULN for non-treated participants 31.
Liver function test values are less than 2x ULN 32. Mean hemoglobin (Hb) <12 g/dL. 33. A
history of red blood cell transfusion within at least 3 months 34. Body mass index (BMI)
between 18 and 30 kg/m2, inclusive, at screening. 35. Contraception use by men or women
should be consistent with local regulations regarding the methods of contraception for
those participating in clinical studies.

36. Willing and able to provide informed consent and comply with all study visits and
procedures 37. Neisseria meningitis vaccination 38. Pneumococcus vaccination 39. Hemophilus
influenzae vaccination

Exclusion Criteria 40. Known or suspected hereditary or acquired complement deficiency 41.
History of clinically significant arterial or venous thrombosis 42. History of
hematopoietic stem cell transplantation 43. History of meningococcal infection 44. Any
significant medical history 45. Active malignancy and/or history of malignancy in the past
5 years 46. Any active viral, bacterial, parasitic, or fungal infection or acute illness
47. Any evidence of sero-positive autoimmune connective tissue diseases 48. Any evidence of
active inflammatory conditions 49. History of previous or current tuberculosis infection
50. Prior splenectomy 51. Major surgery or significant traumatic injury occurring within 3
months 52. Have any other conditions that, in the opinion of the Investigator or Sponsor,
would make the participant unsuitable for inclusion 53. Liver impairment, history of liver
disease, Gilbert's syndrome, or abnormal liver function tests 54. Inadequate organ function
55. Supine systolic blood pressure <90 or >160 mmHg, supine diastolic blood pressure <50 or
>95 mmHg, pulse rate <45 or >100 beats per minute (bpm), or elevated body temperature
(>37.5 ºC) prior to dosing.

56. Positive serology tests for human immunodeficiency virus hepatitis B surface antigen or
hepatitis C virus 57. Willing to continue after enrollment with their current treatment
with a complement inhibitor.

58. Use of vaccines, or changes in any prescription, supplements/vitamins, or over-the
counter medication 59. Treatment with another investigational product or biologic agent
within 30 days 60. History or presence of alcohol abuse 61. Pregnancy

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
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/07/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2025
Actual
Sample size
Target
53
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Nucleus Network Brisbane - Brisbane
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [3] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
4006 - Brisbane
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
3052 - Parkville

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ADARx Pharmaceuticals, Inc.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
ADARx Australia Pty Ltd
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The first-in-human Phase 1 study described herein will evaluate the safety, tolerability,
pharmacokinetics (PK) and pharmacodynamics (PD) of ADX-038 in both healthy volunteers (HV)
and in patients with paroxysmal nocturnal hemoglobinuria (PNH).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05876312
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Richard Friend, MD
Address 0 0
Country 0 0
Phone 0 0
+61 403 415 925
Fax 0 0
Email 0 0
r.friend@nucleusnetwork.com.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05876312