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Trial details imported from ClinicalTrials.gov

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




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

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
Assessment method [1] 0 0
The incidence of adverse events (AE), serious adverse events (SAE), DLT, and AE leading to study drug discontinuation
Timepoint [1] 0 0
approximately up to 2 months
Primary outcome [2] 0 0
Evaluating safety and tolerability through physical exams
Assessment method [2] 0 0
The incidence of clinically significant physical examination (PE) findings
Timepoint [2] 0 0
approximately up to 2 months
Primary outcome [3] 0 0
Changes in 12-lead electrocardiograms (ECG)
Assessment method [3] 0 0
Absolute QTc \> 500 msec and/or QTc change of \> 60 msec from baseline will be evaluated
Timepoint [3] 0 0
approximately up to 2 months
Secondary outcome [1] 0 0
Urine pharmacokinetics (PK) of belcesiran
Assessment method [1] 0 0
Maximum observed concentration (Cmax)
Timepoint [1] 0 0
up to Day 3
Secondary outcome [2] 0 0
Plasma pharmacokinetics (PK) of belcesiran
Assessment method [2] 0 0
Maximum observed concentration (Cmax)
Timepoint [2] 0 0
up to 57 days
Secondary outcome [3] 0 0
Plasma pharmacokinetics (PK) of belcesiran
Assessment method [3] 0 0
Area under the curve (AUC)
Timepoint [3] 0 0
up to 57 days
Secondary outcome [4] 0 0
Urine pharmacokinetics (PK) of belcesiran
Assessment method [4] 0 0
Area under the curve (AUC)
Timepoint [4] 0 0
up to Day 3
Secondary outcome [5] 0 0
Urine pharmacokinetics (PK) of belcesiran
Assessment method [5] 0 0
Minimum observed concentration (Cmin)
Timepoint [5] 0 0
up to Day 3
Secondary outcome [6] 0 0
Plasma pharmacokinetics (PK) of belcesiran
Assessment method [6] 0 0
Minimum observed concentration (Cmin)
Timepoint [6] 0 0
up to 57 days
Secondary outcome [7] 0 0
Plasma pharmacokinetics (PK) of belcesiran
Assessment method [7] 0 0
Time to maximum concentration (Tmax)
Timepoint [7] 0 0
up to 57 days
Secondary outcome [8] 0 0
Urine pharmacokinetics (PK) of belcesiran
Assessment method [8] 0 0
Time to maximum concentration (Tmax)
Timepoint [8] 0 0
up to Day 3
Secondary outcome [9] 0 0
Urine pharmacokinetics (PK) of belcesiran
Assessment method [9] 0 0
Terminal elimination half-life (t1/2)
Timepoint [9] 0 0
up to Day 3
Secondary outcome [10] 0 0
Plama pharmacokinetics (PK) of belcesiran
Assessment method [10] 0 0
Terminal elimination half-life (t1/2)
Timepoint [10] 0 0
up to 57 days
Secondary outcome [11] 0 0
Change in protein concentration
Assessment method [11] 0 0
Changes in A1AT protein concentrations
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
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT04174118