Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04174118




Registration number
NCT04174118
Ethics application status
Date submitted
6/11/2019
Date registered
22/11/2019
Date last updated
28/03/2024

Titles & IDs
Public title
Study of DCR-A1AT in Healthy Adult Volunteers
Scientific title
A Phase 1 Single Ascending Dose, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered Belcesiran in Healthy Adult Volunteers
Secondary ID [1] 0 0
DCR-A1AT-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alpha 1-Antitrypsin Deficiency 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases

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

Experimental: belcesiran - Healthy volunteers will be administered a single dose of belcesiran.

Placebo Comparator: Placebo - Healthy volunteers will be administered a single dose of matching placebo.


Treatment: Drugs: belcesiran
belcesiran will be administered subcutaneously (SC) at dose levels planned.

Treatment: Drugs: Placebo
Sterile normal saline (0.9% NaCL) matching volume of belcesiran doses will be administered subcutaneously (SC).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability
Timepoint [1] 0 0
approximately up to 2 months
Primary outcome [2] 0 0
Evaluating safety and tolerability through physical exams
Timepoint [2] 0 0
approximately up to 2 months
Primary outcome [3] 0 0
Changes in 12-lead electrocardiograms (ECG)
Timepoint [3] 0 0
approximately up to 2 months
Secondary outcome [1] 0 0
Urine pharmacokinetics (PK) of belcesiran
Timepoint [1] 0 0
up to Day 3
Secondary outcome [2] 0 0
Plasma pharmacokinetics (PK) of belcesiran
Timepoint [2] 0 0
up to 57 days
Secondary outcome [3] 0 0
Plasma pharmacokinetics (PK) of belcesiran
Timepoint [3] 0 0
up to 57 days
Secondary outcome [4] 0 0
Urine pharmacokinetics (PK) of belcesiran
Timepoint [4] 0 0
up to Day 3
Secondary outcome [5] 0 0
Urine pharmacokinetics (PK) of belcesiran
Timepoint [5] 0 0
up to Day 3
Secondary outcome [6] 0 0
Plasma pharmacokinetics (PK) of belcesiran
Timepoint [6] 0 0
up to 57 days
Secondary outcome [7] 0 0
Plasma pharmacokinetics (PK) of belcesiran
Timepoint [7] 0 0
up to 57 days
Secondary outcome [8] 0 0
Urine pharmacokinetics (PK) of belcesiran
Timepoint [8] 0 0
up to Day 3
Secondary outcome [9] 0 0
Urine pharmacokinetics (PK) of belcesiran
Timepoint [9] 0 0
up to Day 3
Secondary outcome [10] 0 0
Plama pharmacokinetics (PK) of belcesiran
Timepoint [10] 0 0
up to 57 days
Secondary outcome [11] 0 0
Change in protein concentration
Timepoint [11] 0 0
up to day 57

Eligibility
Key inclusion criteria
- Male or Female aged 18 to 55 years, inclusive. Female participants must be either
surgically sterile or postmenopausal. No women of childbearing potential are eligible
for enrollment.

- Overtly Healthy, as determined by the investigator.

- Serum A1AT protein concentration >100 mg/dL

- Adequate forced expiratory volume in one second (FEV1) and adequate FEV1/forced vital
capacity (FVC) ratio

- Non-smokers with a <2 pack-year history and smoking cessation for at least 6 months
with a negative urinary cotinine test a screening
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Presence of any condition or comorbidities that would interfere with study compliance
or data interpretation or potentially affect participant safety

- Clinically significant abnormal laboratory tests

- Received an experimental drug within past 4 months

- Prior to use of RNAi drug or oligonucleotide-based therapy

- Known human immunodeficiency virus (HIV), hepatitis C virus (HCV), or Hepatitis B
(HBV)

- Serum creatinine or estimated glomerular filtration rate (eGFR) outside normal
reference ranges.

Study design
Purpose of the study
Other
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 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
24/10/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/03/2023
Sample size
Target
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Auckland
Country [2] 0 0
Sweden
State/province [2] 0 0
Uppsala

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a research study to test an experimental study drug (belcesiran, also known as
DCR-A1AT). This drug is being tested to see if it helps people with a rare condition known as
Alpha-1 Antitrypsin Deficiency, or A1ATD. Prior to initiation of this study belcesiran had
not yet been tested in humans. All study participants will be randomly assigned to either
receive the study drug or a placebo. This will allow for the sponsor to compare the effects
of the study drug with that of the placebo. A placebo looks like the study drug but does not
contain any of the study drug.

The main purpose of the first part of the study is to evaluate the safety profile of the
study drug in people who do not have A1ATD. This part of the study will also help find the
dose of the study drug that has an acceptable safety profile for testing.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04174118
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Thomas Bowman, MD
Address 0 0
Dicerna Pharmaceuticals
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