Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001265763
Ethics application status
Approved
Date submitted
7/09/2022
Date registered
23/09/2022
Date last updated
1/03/2024
Date data sharing statement initially provided
23/09/2022
Type of registration
Prospectively 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.
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] 307415 0
DNTH103-AU-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Complement Mediated diseases 326819 0
Condition category
Condition code
Inflammatory and Immune System 324036 324036 0 0
Autoimmune diseases
Blood 324037 324037 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will be conducted in two parts: Part A, the single ascending dose (SAD) portion, and Part B, the multiple ascending dose (MAD) portion. Participants in Part A and Part B will be distinct.

Part A: Up to approximately 72 participants are planned to be enrolled as follows:
• 56 healthy volunteers will be enrolled into seven SAD cohorts, five cohorts receiving study drug as an intravenous (IV) infusion and two receiving study drug as a subcutaneous (SC) injection. Each cohort will enroll 8 participants with 6 participants randomised to receive DNTH103 and 2 participants randomised to receive placebo. The first two subjects dosed in each cohort will be considered sentinel subjects, one each receiving active study drug and placebo.
• The study design allows for an intermediate-dose cohort between two previously studied IV and/or SC dose levels . Therefore, one additional IV cohort and one additional SC cohort may be enrolled, each with 8 participants (16 additional participants).

Part B: Up to approximately 24 participants are planned to be enrolled as follows:
• Up to 16 healthy volunteers will be enrolled into two MAD cohorts; one receiving low dose and one receiving high dose study drug SC. Each cohort will enroll 8 participants with 6 participants randomised to receive DNTH103 and 2 participants randomised to receive placebo.
• The study design allows for an additional cohort, with the dose level and route of administration to be reviewed with the Safety Review Committee (SRC). Therefore, a total of 1 additional cohort with 8 participants may be enrolled.

Part A cohorts:
Single dose DNTH103 or placebo administered on Day 1 (IV or SC) as follows:
• SAD IV1, 1 mg/kg
• SAD IV2, 3 mg/kg
• SAD IV3, 10 mg/kg
• SAD IV4, 30 mg/kg
• SAD IV5, 60 mg/kg
• SAD SC1, 300 mg
• SAD SC2, 600 mg
An additional two intermediate-dose cohorts may also be added (one IV and one SC cohort), with the dose level to be determined (TBD) based on data from the preceding cohorts.

Part B cohorts:
DNTH103 or placebo is scheduled to be administered at 2-week intervals on Day 1, Day 15 and Day 29 (total of three doses) as follows:
• MAD SC1, 300 mg
• MAD SC2, 600 mg

The time separation between Part A and Part B is not fixed. Part B will not commence until safety at the higher dose in Part A is determined through an SRC review.

An additional cohort may also be added, with the dose level and route of administration TBD based on data from the preceding cohorts.

Adherence to intervention will be undertaken via drug accountability.
Intervention code [1] 323897 0
Treatment: Drugs
Comparator / control treatment
Placebo (matching IV infusion or SC injection) and a sterile saline for IV injection, or excipient alone for SC injection.
Control group
Placebo

Outcomes
Primary outcome [1] 331826 0
To evaluate the safety and tolerability of DNTH103 when administered IV or SC as a single dose in healthy adult volunteers.

Safety endpoints include:
• Incidence, severity and relationship of treatment-emergent adverse events (TEAE)
• Incidence, severity and relationship of adverse events of special interest
• Change from baseline in vital signs
• Change from baseline in electrocardiogram (ECG) time intervals
• Change from baseline in clinical laboratory parameters
• Change from baseline in physical examination
Timepoint [1] 331826 0
• Incidence, severity and relationship of treatment-emergent adverse events (TEAE) and AEs of special interest graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (Version 5). Timepoint: Daily from Screening, Confinement (Day -1 to Day 2), Day 3 to Day 57 post-dose (End of Study / Early Termination Visit), Safety Follow Up (87 days post-first dose) & Final Safety Follow Up (determined when the participant’s CH50 level has met normalization criteria).

• Change from baseline in vital signs - Blood pressure and heart rate is assessed using a sphygmomanometer and temperature by thermometer. Timepoints: Screening, Confinement (Day -1, Pre-dose vital signs assessments, on Day 1, should be performed within 1.5 hours prior to dosing. On Day 1, vital signs assessments, for participants receiving DNTH103 IV, are to be performed at the beginning of infusion, at the end of infusion (EOI), and at 1, 2, 4 and 8 hours (± 15 minutes) post-dose and Day 2, Day 3, Day 5, Day 8, Day 15, Day 29 and Day 57 post-dose (EOS/ET). On Day 1, vital signs assessments, for participants receiving DNTH103 SC, are to be performed directly after completion of injection(s) and at 1, 2, 4 and 8 hours (± 15 minutes) post-dose and Day 2, Day 3, Day 5, Day 8, Day 15, Day 29 and Day 57 post-dose (End of Study / Early Termination Visit)

• Change from baseline in electrocardiogram (ECG) parameters - All electrocardiograms (ECGs) will be in triplicate at Screening, Confinement (Day -1), for participants receiving DNTH103 IV, Post-dose ECG on Day 1 is to be performed 1 hour (± 15 minutes) after EOI and Day 3, Day 8 and Day 57 post-dose (End of Study / Early Termination Visit). For participants receiving DNTH103 SC, Post-dose ECG on Day 1 is to be performed 1 hour (± 15 minutes) after completion of injection(s), Day 3, Day 8 and Day 57 post-dose (End of Study / Early Termination Visit).

• Change from baseline in clinical laboratory parameters, including haematology, serum chemistry, coagulation and urinalysis - Blood and urine samples taken at Screening, Confinement (Day -1), Days 2 and 3 collected at 24 hours (Day 2) and 48 hours (Day 3) post- Day 1 dose, Day 8, Day 29 and Day 57 post-dose (End of Study / Early Termination Visit)

• Change from baseline in physical examination - Full physical examinations will include, at a minimum, assessment of the following: general appearance, head, ears, eyes, nose and throat, neck (including thyroid and lymph nodes), respiratory system, cardiovascular system, gastrointestinal system, renal system, neurological condition, musculoskeletal system, skin and any other focused assessments suggested by the presence of specific symptoms and will occur at Screening and Day 57 post-dose (End of Study / Early Termination Visit).

Symptom-directed physical examination only (focused assessments suggested by the presence of specific symptoms). Examination to be performed if deemed required by a medically qualified staff member, in the case of participant-reported specific symptoms. Pre-dose physical examination assessments should be performed on the scheduled day, at any time prior to dosing on Day -1, Day 1, Day 2, Day 3, Day 5, Day 8, Day 15 and Day 29 post-dose. All other physical examinations may be performed at any time on the scheduled day. Additional assessments may be performed at the discretion of the PI.
Primary outcome [2] 331969 0
To evaluate the safety and tolerability of DNTH103 when administered IV or SC as multiple doses in healthy adult volunteers.

Safety endpoints include:
• Incidence, severity and relationship of treatment-emergent adverse events (TEAE)
• Incidence, severity and relationship of adverse events of special interest
• Change from baseline in vital signs
• Change from baseline in electrocardiogram (ECG) time intervals
• Change from baseline in clinical laboratory parameters
• Change from baseline in physical examination
Timepoint [2] 331969 0
• Incidence, severity and relationship of treatment-emergent adverse events (TEAE) and AEs of special interest graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (Version 5). Timepoint: Daily from Screening, Confinement (Day -1 to Day 2), Day 3, Day 5, Day 8 post-first dose, Confinement (Day 14 to Day 15), Day 22 post-first dose, Confinement (Day 28 to Day 29), Day 31, 33, 36, 43, 57, 71 and Day 85 post-first dose (End of Study/Early Termination Visit) Safety Follow up (115 days post-first dose) & Final Safety Follow Up (determined when the participant’s CH50 level has met normalization criteria).

• Change from baseline in vital signs - Blood pressure and heart rate is assessed using a sphygmomanometer and temperature by thermometer.
Timepoints: Screening, Confinement (Day -1, Day 1 Pre-dose and Post-dose at 1hr, 2hrs, 4hrs and 6hrs), then on Day 3, Day 5, Day 8 post-dose, Confinement (Day 14, Day 15 pre-dose and post-dose 1hr, 2hrs, 4hrs and 6hrs), Confinement (Day 28, Day 29 pre-dose and post-dose at 1hr, 2hrs, 4hrs and 6hrs,) Day 31, 33, 36, 43, 57, 71 and Day 85 post-first dose (End Of Study/Early Termination).

• Change from baseline in electrocardiogram (ECG) parameters - All electrocardiograms (ECGs) will be in triplicate at Screening, Confinement (Day -1, Day 1 Post-dose at 1hr), Confinement (Day 14, Day 15 Post-dose at 1hr), Confinement (Day 28, Day 29 Post-dose at 1 hr), Day 57 and Day 85 post-first dose (End Of Study/Early Termination).

• Change from baseline in clinical laboratory parameters, including haematology, serum chemistry, coagulation and urinalysis - Blood and urine samples taken at Screening, Confinement (Day -1), Day 3, Day 8 post-dose, Confinement (Day 14), Confinement (Day 28), Day 31, Day 36, Day 43, Day 57 and Day 85 post-first dose (End Of Study/Early Termination).

• Change from baseline in physical examination - Full physical examinations will include, at a minimum, assessment of the following: general appearance, head, ears, eyes, nose and throat, neck (including thyroid and lymph nodes), respiratory system, cardiovascular system, gastrointestinal system, renal system, neurological condition, musculoskeletal system, skin and any other focused assessments suggested by the presence of specific symptoms and will occur at Screening and Day 85 post-first dose (End Of Study/Early Termination).

Symptom-directed physical examination only (focused assessments suggested by the presence of specific symptoms) from Confinement (Day -1, Day 1), Day 3, Day 5, Day 8 post-dose, Confinement (Day 14, Day 15), Confinement (Day 28, Day 29), Days 31, 33, 36, 43, 57 and 71 post-first dose.
Secondary outcome [1] 411294 0
To evaluate the pharmacokinetics (PK) of DNTH103 when administered IV or SC as a single dose in healthy adult volunteers. Pharmacokinetic endpoints may include (but are not limited to), if feasible:
• Maximum concentration (Cmax)
• Time to maximum concentration (Tmax)
• Terminal elimination half-life (t½)
• Area under the concentration versus time curve from time zero to the last measurable time point post-dose (AUC0–t)
• Area under the concentration versus time curve from time zero to 14 days post-dose (AUC0–14)
• Area under the concentration versus time curve for the dosing interval (AUC0–tau) (Part B only)
• Area under the concentration versus time curve from time zero to infinity (AUC0–inf)
• Clearance (CL) or apparent CL (CL/F)
• Volume of distribution of central compartment (V1) or apparent volume of distribution (V/F)
• Absolute bioavailability (Fabs)
Timepoint [1] 411294 0
Plasma PK samples collected at the following timepoints:

Day 1 Pre-dose, End of Infusion IV (EOI) or 1 hr post-dose injection (SC), 5 hrs post-dose IV (EOI) or 6 hrs post-dose injection (SC), Day 2 23 hrs post-dose IV (EOI) or 24 hrs post-dose injection (SC), Day 3 47 hrs post-dose IV (EOI) or 48 hrs post-dose injection (SC), 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 [2] 411295 0
To evaluate the pharmacokinetics (PK) of DNTH103 when administered IV or SC as multiple doses in healthy adult volunteers. Pharmacokinetic endpoints may include (but are not limited to), if feasible:
• Maximum concentration (Cmax)
• Time to maximum concentration (Tmax)
• Terminal elimination half-life (t½)
• Area under the concentration versus time curve from time zero to the last measurable time point post-dose (AUC0–t)
• Area under the concentration versus time curve from time zero to 14 days post-dose (AUC0–14)
• Area under the concentration versus time curve for the dosing interval (AUC0–tau) (Part B only)
• Area under the concentration versus time curve from time zero to infinity (AUC0–inf)
• Clearance (CL) or apparent CL (CL/F)
• Volume of distribution of central compartment (V1) or apparent volume of distribution (V/F)
• Absolute bioavailability (Fabs)
Timepoint [2] 411295 0
Plasma PK samples collected at the following timepoints:

Day 1 Pre-dose, End of Infusion (EOI) Post-dose, 6 hrs post-dose, Day 3, Day 5, Day 8 post-dose, Day 15 Pre-dose, Day 29 Pre-dose, End of Infusion (EOI) 6 hrs post-dose, Day 31, Day 33, Day 36, Day 43, Day 57, Day 71, Day 85 post-first dose (End of Study) and Early Termination, Monthly visits for 6 months post-first dose, Final Safety Follow-up (determined when the participant’s CH50 level has met normalization criteria).
Secondary outcome [3] 411296 0
To evaluate the immunogenicity of DNTH103 when administered IV or SC as a single dose in healthy adult volunteers.

Immunogenicity endpoints include:
• Incidence of anti-drug antibody (ADA) to DNTH103
Timepoint [3] 411296 0
Anti-Drug Antibody measurement timepoints are 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] 411297 0
To evaluate the immunogenicity of DNTH103 when administered IV or SC as multiple doses in healthy adult volunteers.

Immunogenicity endpoints include:
• Incidence of anti-drug antibody (ADA) to DNTH103
Timepoint [4] 411297 0
Anti-Drug Antibody measurement timepoints are as follows:

Day 1 Pre-first dose
Day 29 Pre-third dose
Day 57 post-first dose
Day 85 post-first 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 [5] 411298 0
To evaluate the effect of DNTH103 on the classical complement pathway when administered IV or SC as a single dose in healthy adult volunteers. Pharmacodynamic endpoints include:
• Complement system classical pathway (CP) inhibition measures in serum ex vivo by the WIESLAB® assay
• CH50 (complement haemolysis 50%) in serum ex vivo
Timepoint [5] 411298 0
Serum PD (Pharmacodynamic) samples collected at the following timepoints:

Day 1 Pre-dose, End of Infusion IV (EOI) or 1 hr post-dose injection (SC), 5 hrs post-dose IV (EOI) or 6 hrs post-dose injection (SC), Day 2 23 hrs post-dose IV (EOI) or 24 hrs post-dose injection (SC), Day 3 47 hrs post-dose IV (EOI) or 48 hrs post-dose injection (SC), 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 [6] 411769 0
To evaluate the effect of DNTH103 on the classical complement pathway when administered IV or SC as multiple doses in healthy adult volunteers Pharmacodynamic endpoints include:
• Complement system classical pathway (CP) inhibition measures in serum ex vivo by the WIESLAB® assay
• CH50 (complement haemolysis 50%) in serum ex vivo
Timepoint [6] 411769 0
Serum PD (Pharmacodynamic) samples collected at the following timepoints:

Day 1 Pre-dose, End of Infusion (EOI) Post-dose, 6 hrs post-dose, Day 3, Day 5, Day 8, Day 15 Pre-dose, Day 29 Pre-dose, End of Infusion (EOI) 6 hrs post-dose, Day 31, Day 33, Day 36, Day 43, Day 57, Day 71, Day 85 post-first dose (End of Study) and Early Termination, Monthly visits for up to 6 months post-first 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 3 consecutive 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
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment will be maintained during this study. Sealed participant-specific code break envelopes will be produced by the unblinded statistician(s) and will be retained at the clinical facility in a secure, accessible location.

The sponsor, the PI, and clinical study personnel responsible for the determining study participant eligibility will be blinded to which group the participant will be assigned to.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The allocation to DNTH103 or placebo will be performed using a block randomisation algorithm and will be documented in the study randomisation schedule.
Randomisation numbers assigned will be in accordance with the randomisation schedule. The randomisation schedules will be maintained under controlled access. As the study is double-blinded, sealed participant-specific code break envelopes will be produced by the unblinded statistician(s) and will be retained at the clinical facility in a secure, accessible location.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
This study is a double-blind study. Those blinded to study drug assignment include the Investigator, site staff (other than pharmacists), Sponsor, the PI, clinical study personnel participating in participants’ care or clinical evaluations, and the study participants.
Those unblinded to study drug assignment include the statisticians preparing the randomisation and code break envelopes, the pharmacist preparing individual doses of study drug and the dedicated clinical supply manager.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
This is a first in human study for DNTH103. As such, no formal sample size calculations have been performed. The number of participants in each treatment arm is considered sufficient to achieve the objectives of the study.

Analysis Populations

Safety Population
The safety population will consist of all randomised participants who received any amount of study drug. Participants will be analysed according to actual treatment received.

Pharmacokinetic Population
The PK population will include all randomised participants who received treatment where there is at least one post-dose measurement of serum PK concentration data. Participants will be analysed according to treatment received.

The PK population will be used for the summaries of all PK data.

Pharmacodynamic Population
The PD population will include all randomised participants who receive any amount of study treatment, who have at least 1 evaluable post-dose PD parameter and will be analysed based on the actual treatment received.

The PD population will be used for the summaries of all PD data.

Immunogenicity Population
The immunogenicity population will include all randomised participants who receive any
amount of study treatment, who have at least 1 evaluable post-dose immunogenicity parameter, and will be analysed based on the actual treatment received.

The immunogenicity population will be used for the summaries of all immunogenicity data.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
17/11/2022
Actual
19/11/2022
Date of last participant enrolment
Anticipated
31/03/2024
Actual
Date of last data collection
Anticipated
15/09/2024
Actual
Sample size
Target
96
Accrual to date
65
Final
Recruitment outside Australia
Country [1] 24889 0
New Zealand
State/province [1] 24889 0
Christchurch

Funding & Sponsors
Funding source category [1] 311691 0
Commercial sector/Industry
Name [1] 311691 0
Dianthus Therapeutics, Inc.
Country [1] 311691 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Dianthus Therapeutics, Inc.
Address
203 Crescent Street Building 17,
Suite 102B
Waltham MA 02453
Country
United States of America
Secondary sponsor category [1] 313146 0
Commercial sector/Industry
Name [1] 313146 0
Avance Clinical Pty Ltd
Address [1] 313146 0
213 Glynburn Rd, Firle, SA 5070 Australia
Country [1] 313146 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311144 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 311144 0
Ministry of Health
133 Molesworth Street
Wellington 6011
Ethics committee country [1] 311144 0
New Zealand
Date submitted for ethics approval [1] 311144 0
30/08/2022
Approval date [1] 311144 0
29/09/2022
Ethics approval number [1] 311144 0
2022 FULL 13249

Summary
Brief summary
DNTH103 is being developed as a potential treatment for autoimmune and inflammatory diseases. This Phase I study will investigate the effects of DNTH103 in healthy participants when given as a single (ascending /SAD) dose subcutaneously (SC) or intravenously (IV)
or multiple (ascending/MAD) SC doses. This is a first-in-human, randomised, placebo-controlled, ascending dose study.
Trial website
Trial related presentations / publications
Public notes
Study Enrolment Inclusion Criteria:
10. Must be fully immunized for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV 2, COVID-19) based on the country-specific definitions in place at the time of Screening, and have a negative COVID-19 polymerase chain reaction (PCR) test within 7 days prior to each study drug administration.

Contacts
Principal investigator
Name 120098 0
Dr Christian Schwabe
Address 120098 0
New Zealand Clinical Research (NZCR), Ground Floor 3, Ferncroft St, Grafton, Auckland 1010, New Zealand
Country 120098 0
New Zealand
Phone 120098 0
+64 21 461766
Fax 120098 0
Email 120098 0
Christian.Schwabe@nzcr.co.nz
Contact person for public queries
Name 120099 0
Dr Christian Schwabe
Address 120099 0
NZCR, Ground Floor 3, Ferncroft St, Grafton, Auckland 1010, New Zealand
Country 120099 0
New Zealand
Phone 120099 0
+64 21 461766
Fax 120099 0
Email 120099 0
Christian.Schwabe@nzcr.co.nz
Contact person for scientific queries
Name 120100 0
Dr Christian Schwabe
Address 120100 0
NZCR, Ground Floor 3, Ferncroft St, Grafton, Auckland 1010, New Zealand
Country 120100 0
New Zealand
Phone 120100 0
+64 21 461766
Fax 120100 0
Email 120100 0
Christian.Schwabe@nzcr.co.nz

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


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.