Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000352505
Ethics application status
Approved
Date submitted
13/03/2024
Date registered
27/03/2024
Date last updated
27/03/2024
Date data sharing statement initially provided
27/03/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase 1, Placebo-Controlled, Single/Multiple Ascending Dose Study of DNTH103 Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Intravenous and Subcutaneous Administration in Healthy Volunteers. (Part C)
Scientific title
A Phase 1, Placebo-Controlled, Single/Multiple Ascending Dose Study of DNTH103 Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Intravenous and Subcutaneous Administration in Healthy Volunteers.
Secondary ID [1] 311441 0
DNTH103-AU-001
Universal Trial Number (UTN)
Trial acronym
Linked study record
This record is a sub study of ACTRN12622001265763

Health condition
Health condition(s) or problem(s) studied:
Complement Mediated diseases 332729 0
Condition category
Condition code
Inflammatory and Immune System 329448 329448 0 0
Autoimmune diseases
Blood 329449 329449 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will be conducted in three parts. Part A and Part B have already been registered and this registration of Part C will be evaluating DNTH103 PK following administration of human normal immunoglobulin (Ig)G. Part C will be open label and will not be placebo controlled.

Up to a maximum of 8 participants will be enrolled in a single cohort (IV7) receiving DNTH103 at a single dose level as an intravenous (IV) infusion or a subcutaneous injection (SC) following administration of the Immunoglobulin G (IgG) ,Privigen® NZ (10% [100 g/L]), solution for IV infusion. No sentinel dosing is required.

Single dose DNTH103, administered on Day 1 after administration of Privigen NZ solution for IV infusion on Days -8 and -7

Initial Medication: Intravenous immunoglobulin (IVIg) G, Privigen (10% [100 g/L]) for infusion, at the following dose:
• IV7, 0.5 g/kg of body weight per day for 2 consecutive days (total dose: 1 g/kg)

Investigational Product: DNTH103 IV infusion, 1 week after Privigen NZ solution:
• IV7, 10 mg/kg

Investigational Product: DNTH103 SC injection, 1 week after Privigen NZ solution:
• IV7, 600 mg

Part C will be initiated after dosing and SRC review is completed for Part A cohort SAD IV4.

Adherence to intervention will be undertaken via drug accountability.
Intervention code [1] 327882 0
Treatment: Drugs
Comparator / control treatment
No Control Group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 337264 0
To evaluate the pharmacokinetics (PK) of DNTH103 when administered IV following administration of IgG, as a single dose in healthy adult volunteers.
Timepoint [1] 337264 0
Blood plasma samples to be collected Day 1 pre-dose, End of Infusion IV (EOI), 5 hrs post-dose IV (EOI), Day 2 23 hrs post-dose IV (EOI), Day 3 47 hrs post-dose IV (EOI), Day 5, Day 8, Day 15, Day 29, Day 57 post-dose (End of Study) and Early Termination, Monthly visits for up to 6 months post-dose, Final Safety Follow-up (determined when the participant’s CH50 level has met normalization criteria).
Primary outcome [2] 337600 0
To evaluate the PK of DNTH103 when administered SC following administration of IgG, as a single dose in healthy adult volunteers.
Timepoint [2] 337600 0
Blood plasma samples to be collected Day 1 pre-dose, 5 hrs post-dose, Day 2 23 hrs post-dose, Day 3 47 hrs post-dose, Day 5, Day 8, Day 15, Day 29, Day 57 post-dose (End of Study) and Early Termination, Monthly visits for up to 6 months post-dose, Final Safety Follow-up (determined when the participant’s CH50 level has met normalization criteria).
Secondary outcome [1] 431266 0
To evaluate the immunogenicity of DNTH103 when administered IV following administration of IgG as a single dose in healthy adult volunteers.
Timepoint [1] 431266 0
Blood plasma samples collected and measured as follows:
Day 1 Pre-dose
Day 29 post-dose
Day 57 post-dose (End of Study) and Early Termination
Final Safety Follow-up visit (determined when the participant’s CH50 level has met normalization criteria).
Secondary outcome [2] 431267 0
To evaluate the effect of DNTH103 on the classical complement pathway when administered IV following administration of IgG as a single dose in healthy adult volunteers.
Timepoint [2] 431267 0
Blood serum PD samples collected at the following timepoints:
Day 1 Pre-dose, End of Infusion IV (EOI), 5 hrs post-dose IV (EOI), Day 2 23 hrs post-dose IV (EOI), Day 3 47 hrs post-dose IV (EOI), Day 5, Day 8, Day 15, Day 29, Day 57 post-dose (End of Study) and Early Termination, Monthly visits for up to 6 months post -dose, Final Safety Follow-up (determined when the participant’s CH50 level has met normalization criteria).
Secondary outcome [3] 432471 0
To evaluate the immunogenicity of DNTH103 when administered SC following administration of IgG as a single dose in healthy adult volunteers.
Timepoint [3] 432471 0
Blood plasma samples collected and measured as follows:
Day 1 Pre-dose
Day 29 post-dose
Day 57 post-dose (End of Study) and Early Termination
Final Safety Follow-up visit (determined when the participant’s CH50 level has met normalization criteria).
Secondary outcome [4] 432472 0
To evaluate the effect of DNTH103 on the classical complement pathway when administered SC following administration of IgG as a single dose in healthy adult volunteers.
Timepoint [4] 432472 0
Blood serum PD samples collected at the following timepoints:
Day 1 pre-dose, 5 hrs post-dose, Day 2 23 hrs post-dose, Day 3 47 hrs post-dose, Day 5, Day 8, Day 15, Day 29, Day 57 post-dose (End of Study) and Early Termination, Monthly visits for up to 6 months post -dose, Final Safety Follow-up (determined when the participant’s CH50 level has met normalization criteria).

Eligibility
Key inclusion criteria
1. Adult males and females, 18 to 65 years of age (inclusive) at Screening.
2. Body mass index less than or equal to 32 kg/m2, with a body weight (to 1 decimal place) greater than or equal to 45 kg and less than or equal to 100 kg at Screening.
3. Be non-smokers (including tobacco, e-cigarettes and marijuana) for at least 3 months prior to first study drug administration and have a negative test for cotinine at the Screening visit and at check-in on Day -1.
Note: Subjects who smoke no more than 2 cigarettes or equivalent per week may be included in the study but must be willing to abstain from smoking 7 days prior to admission and during the confinement period. Subjects must have a negative test for nicotine prior to check-in on Day -1.
4. Medically healthy without clinically significant abnormalities (in the opinion of the Investigator) at the Screening visit and after check-in on Day -1, prior to dose administration on Day 1, including:
a. Physical examination without any clinically significant findings.
b. Systolic blood pressure in the range of 90 to 150 mmHg (inclusive) and diastolic blood pressure in the range of 50 to 90 mmHg (inclusive) after 5 minutes rest in a semi-supine position.
c. Heart rate (HR) in the range of 40 to 90 bpm (inclusive) after 5 minutes rest in a semi- supine position.
d. Body temperature (tympanic) in the range 35.5°C to 37.7°C (inclusive).
e. No clinically significant findings in serum chemistry, haematology, coagulation and urinalysis tests as per PI.
f. Triplicate 12-lead ECG performed with no clinically significant abnormalities.
5. Female volunteers must:
a. Be of nonchildbearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before Screening) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause, and a follicle-stimulating hormone (FSH)level >40 IU/L at the Screening visit), or
b. If of childbearing potential, must agree not to donate ova, not to attempt to become pregnant and, if engaging in sexual intercourse with a male partner, must agree to use an acceptable method of contraception from signing the consent form until at least 90 days after the last dose of the study drug.
6. Male volunteers must agree not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use an acceptable method of contraception from signing the consent form until at least 90 days after the last dose of study drug.
7. Previously immunized against encapsulated bacterial pathogens as per country-specific guidelines (Neisseria meningitis, Haemophilus influenza, and Streptococcus pneumonia within past 5 years) or willing and able to be vaccinated during the Screening Period and at least 14 days prior to study drug administration on Day 1.
8. Haematocrit (HCT) and /Haemoglobin (Hb) levels within normal limits for age and sex at Screening and on Day -1, prior to dose administration.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or major surgery within 3 months prior to screening determined by the PI to be clinically significant.
2. History of autoimmune disease or positive autoantibody test result at Screening.
3. History of active malignancy within 5 years prior to Screening, except basal cell carcinoma of the skin, curatively resected squamous cell carcinoma of the skin, cervical carcinoma in situ curatively treated or low-grade prostate adenocarcinoma for which appropriate management is observation alone.
4. Liver test results during Screening or at check-in day (Day 1) that are elevated more than 1.5-fold above the ULN for gamma glutamyl transferase, bilirubin (total), aspartate aminotransferase (AST) or alanine aminotransferase (ALT), unless a diagnosis of Gilbert syndrome. For history of Gilbert syndrome, the limit is extended to 2-fold above the ULN.
The above assessment may be repeated once, if abnormal values were recorded in the first instance, at the discretion of the PI.
5. Positive test results for human immunodeficiency virus (HIV-1 or HIV-2) antibody/antigen, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the Screening visit. Healthy volunteers who have no evidence of cirrhosis, have completed a curative intent regimen for HCV, and deemed by a gastroenterologist to have no active HCV will not be excluded.
6. Estimated creatinine clearance (CrCl) < 60 mL/min during Screening or at check-in day (Day -1) using the Cockcroft-Gault formula or serum creatinine more than 1.5-fold above the ULN.
7. History of substance abuse or alcohol abuse (defined as more than 10 standard drinks per week or regularly consuming more than 4 standard drinks on any one day; within 12 weeks prior to the Screening visit.
8. Positive drugs of abuse or alcohol breath test results at the Screening visit or at check-in (Day -1).
9. Use of any prescription or over-the-counter medication (including herbal products, vitamins, health supplements, diet aids, and hormone supplements) within 2 weeks or 5 half-lives of the medication(whichever is longer) prior to the first study drug administration, except use of contraceptives, occasional use of paracetamol (doses of 500 mg up to every 6 hours or 2 g per day maximum for no more than 3consecutive days) or where in the opinion of the Investigator, particular use would not interfere with the volunteer’s ability to participate in the trial.
10. Demonstrated clinically significant (required intervention, e.g., emergency room visit, epinephrine administration) allergic reactions (e.g., food, drug, or atopic reactions, asthmatic episodes) which, in the opinion of the Investigator, would interfere with the volunteer’s ability to participate in the trial.
11. Administration of any live, attenuated vaccines within 30 days and all other vaccinations within 14 days prior to study drug administration.
12. For women of childbearing potential (WOCBP), a positive serum pregnancy test at the Screening visit or a positive urine pregnancy test (with confirmatory serum pregnancy test) at check-in (Day -1).
13. Females who are breastfeeding or planning to breast feed at any time during the study.
14. Donation of blood or plasma within 30 days prior to first study drug administration, or loss of whole blood of more than 500 mL within 30 days prior to first study drug administration, or receipt of a blood transfusion within 1 year of first study drug administration.
15. Participation in another clinical trial of an investigational drug within 60 days or 5 half-lives of the investigational agent (whichever is longer) prior to the first study drug administration.
16. Any other condition, including mental illness or prior therapy that in the opinion of the Investigator would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
12/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
8
Accrual to date
3
Final
Recruitment outside Australia
Country [1] 26128 0
New Zealand
State/province [1] 26128 0
Christchurch

Funding & Sponsors
Funding source category [1] 315718 0
Commercial sector/Industry
Name [1] 315718 0
Dianthus Therapeutics, Inc.
Country [1] 315718 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Dianthus Therapeutics, Inc.
Address
Country
United States of America
Secondary sponsor category [1] 317824 0
Commercial sector/Industry
Name [1] 317824 0
Avance Clinical Pty Ltd
Address [1] 317824 0
Country [1] 317824 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314582 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 314582 0
Ethics committee country [1] 314582 0
New Zealand
Date submitted for ethics approval [1] 314582 0
30/08/2022
Approval date [1] 314582 0
29/09/2022
Ethics approval number [1] 314582 0
2022 FULL 13249

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 132082 0
Dr Christian Schwabe
Address 132082 0
New Zealand Clinical Research (NZCR), Ground Floor 3, Ferncroft St, Grafton, Auckland 1010, New Zealand
Country 132082 0
New Zealand
Phone 132082 0
+64 21 461766
Fax 132082 0
Email 132082 0
[email protected]
Contact person for public queries
Name 132083 0
Christian Schwabe
Address 132083 0
New Zealand Clinical Research (NZCR), Ground Floor 3, Ferncroft St, Grafton, Auckland 1010, New Zealand
Country 132083 0
New Zealand
Phone 132083 0
+64 21 461766
Fax 132083 0
Email 132083 0
[email protected]
Contact person for scientific queries
Name 132084 0
Christian Schwabe
Address 132084 0
New Zealand Clinical Research (NZCR), Ground Floor 3, Ferncroft St, Grafton, Auckland 1010, New Zealand
Country 132084 0
New Zealand
Phone 132084 0
+64 21 461766
Fax 132084 0
Email 132084 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.