Heart FailurePhase 1NCT04630067
Assessment of Safety, Tolerability, Immunogenicity, and Pharmacokinetics of AZD3427
A Phase 1 study testing AZD3427 in people with Heart Failure, run by AstraZeneca at 10 sites in United States.
Trial summary
This first-time-in-human (FTIH) study will be conducted to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of single doses of AZD3427 in healthy volunteers and multiple doses of AZD3427 in patients with heart failure (HF). Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Heart Failure
- What is being tested?
- AZD3427
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 105 participants
- Where
- 10 sitesUnited States
- Study dates
- 17 Nov 2020to 14 Sep 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Part A will include healthy men and non-pregnant, non-lactating females of non-childbearing potential with a body mass index (BMI) of 18-30 kg/m^2 and a weight of 55-100 kg. One cohort will require participants be of Japanese descent
- Part B will include men and non-pregnant, non-lactating females of non-childbearing potential
- Participants have a BMI of 18-40 kg/m^2 and a weight of 55-136 kg
- Participants with a diagnosis of stage C HF New York Heart Association (NYHA) Class I-III on stable medical therapy for at least 12 weeks
- Participants with diagnosis of HFrEF will be defined as those with EF ≤ 40% and HF with EF ≥ 41%
- Participants either with N-terminal prohormone of brain natriuretic peptide (NT-proBNP) > 125 pg/mL or BNP > 35 pg/mL (46)
Who cannot join
- Both Part A and Part B will exclude participants with any of the following:
- Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of study drug or planned surgical procedure before study completion
- History of vascular and left ventricular aneurysms or prior dissections
- Any history of joint hypermobility, Marfan's syndrome, or any connective tissue disorder
- Clinical signs and symptoms consistent with Coronavirus disease-19 or confirmed infection within the last 4 weeks
- History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity injection devices or to drugs with a similar chemical structure or class to AZD3427 or any component of AZD3427
Show all 37Show fewer
- In addition, Part A will exclude participants with any of the following:
- Alanine Aminotransferase (ALT) > Upper limit of normal (ULN)
- Aspartate Aminotransferase (AST) > ULN
- Total bilirubin > ULN (unless due to Gilbert's syndrome)
- Creatinine > ULN
- White blood cell (WBC) count < Lower limit of normal (LLN)
- Hemoglobin < LLN
- Prolonged QTcF > 450 m
- Shortened QTcF < 340 ms
- Family history of long QT syndrome
- PR (PQ) interval shortening < 120 ms (PR > 110 ms but < 120 ms is acceptable if there is no evidence of ventricular pre-excitation)
- PR (PQ) interval prolongation (> 240 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third-degree atrioventricular (AV) block, or AV dissociation
- Persistent or intermittent complete bundle branch block, incomplete bundle branch block, or intraventricular conduction delay with QRS > 110 ms. Participants with QRS > 110 ms but < 115 ms are acceptable if there is no evidence of eg, ventricular hypertrophy or pre-excitation
- In addition, Part B will exclude participants with any of the following:
- Atrial fibrillation or flutter occurring in the past year
- Clinically significant ventricular arrhythmias under treatment
- High-degree AV block II-III or sinus node dysfunction
- Implanted permanent pacemaker or implantable cardioverter defibrillator for which the participant is pacing-dependent
- Severe right-sided valvular heart disease; severe mitral regurgitation; moderate or severe mitral stenosis, severe aortic regurgitation and mild, moderate or severe aortic stenosis
- Other conditions where vasodilatory therapy may be contraindicated (hypertrophic obstructive cardiomyopathy, and restrictive cardiomyopathy)
- Congenital heart disease
- NYHA HF Class IV
- Occurrence in the last 6 months of acute coronary syndrome, percutaneous coronary intervention, cerebrovascular accident or transient ischemic attack, HF hospitalization; history or suspicion of cardiac amyloidosis
- ALT > 1.5 × ULN
- AST > 1.5 × ULN
- Total bilirubin > ULN (unless due to Gilbert's syndrome)
- Impaired renal function, defined as eGFR < 30 mL/min/1.73m^2 assessed by the Chronic Kidney Disease Epidemiology Collaboration equation
- WBC < LLN
- Hemoglobin < 10g/L
- PR (PQ) interval prolongation (> 220 ms)
- Participants with persistent BBB and QRS (ECG interval measured from the onset of the QRS complex to the J point) duration > 130 ms. Participants with intraventricular conduction delay and QRS duration < 130 ms
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Research Site
Brooklyn, Maryland, 21225
Research Site
Daytona Beach, Florida, 32117
Research Site
Detroit, Michigan, 48202
Research Site
Doral, Florida, 33166
Research Site
Glendale, California, 91206
Research Site
Hallandale, Florida, 33009
Research Site
Houston, Texas, 77030
Research Site
Jacksonville, Florida, 32216
Research Site
Little Rock, Arkansas, 72204
Research Site
Owensboro, Kentucky, 42303
About this study
Official title: A Phase Ia/b Randomized, Single-blinded, Placebo-controlled Study to Evaluate the Safety, Tolerability, Immunogenicity, and Pharmacokinetics of Single Ascending Doses of AZD3427 in Healthy Volunteers and Multiple Ascending Doses of AZD3427 in Patients With Heart Failure (HFrEF and HF With EF ≥ 41%)
This first-time-in-human (FTIH) study will be conducted to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of single doses of AZD3427 in healthy volunteers and multiple doses of AZD3427 in patients with heart failure (HF).
Read the detailed description
This is a multi-center single and multiple ascending dose study (SAD and MAD).
Part A (SAD) will include 7 cohorts (8 healthy volunteers in each cohort) and will randomize to AZD3427 or placebo, in a 6:2 ratio. One cohort will entirely include participants of Japanese descent.
Part B (MAD) will include 6 cohorts (8 heart failure patients in each cohort) and will randomize to AZD3427 or placebo in a 6:2 ratio. Of these, 3 cohorts will contain participants with heart failure with reduced ejection fraction [HFrEF] and the other 3 cohorts will comprise of participants with heart failure with HF with ejection fraction (EF) ≥ 41%. There will be a maximum screening period of 27 days. Participants in part A and B will undergo study drug administration on Day 1. In addition, participants in part B will return for 4 additional doses on Days 8, 15, 22, and 29. Participants will be followed for at least 50 days after the last dose of study drug.
- Conditions
- Heart Failure
- Being tested
- AZD3427, Placebo
- Keywords
- Heart failure with reduced ejection fraction, Heart failure with ejection fraction of ≥ 41%, AZD3427, First-time-in-human
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD3427Drug
Participants will receive SC or IV dose of AZD3427 as per the arm they are randomized.
PlaceboDrug
Participants will receive SC or IV dose of placebo matched to AZD3427 as per the arm they are randomized.
| Study group | Role | What they receive |
|---|---|---|
| AZD3427: Cohort 1a | Experimental | Participants will receive single SC dose A of AZD3427 on Day 1. Receives: Drug: AZD3427 |
| AZD3427: Cohort 2a | Experimental | Participants will receive single SC dose B of AZD3427 on Day 1. Receives: Drug: AZD3427 |
| AZD3427: Cohort 3a | Experimental | Participants will receive single SC dose C of AZD3427 on Day 1. Receives: Drug: AZD3427 |
| AZD3427: Cohort 4a | Experimental | Participants will receive single SC dose D of AZD3427 on Day 1. Receives: Drug: AZD3427 |
| AZD3427: Cohort 5a | Experimental | Participants will receive single IV dose E of AZD3427 on Day 1. Receives: Drug: AZD3427 |
| AZD3427: Cohort 6a | Experimental | Participants of Japanese descent will receive single SC dose anticipated equal to the highest dose of AZD3427 in the global cohorts on Day 1. Receives: Drug: AZD3427 |
| AZD3427: Cohort 7a | Experimental | Participants will receive single SC dose F of AZD3427 on Day 1 Receives: Drug: AZD3427 |
| Part A: Placebo | Placebo comparator | Participants will receive single SC or IV dose of placebo matched to AZD3427 on Day 1. Receives: Drug: Placebo |
| AZD3427: Cohort 1b | Experimental | Participants with HFrEF will receive SC dose A of AZD3427 on Days 1, 8, 15, 22, and 29. Receives: Drug: AZD3427 |
| AZD3427: Cohort 2b | Experimental | Participants with HF with EF ≥ 41% will receive SC dose A of AZD3427 on Days 1, 8, 15, 22, and 29. Receives: Drug: AZD3427 |
| AZD3427: Cohort 3b | Experimental | Participants with HFrEF will receive SC dose B of AZD3427 on Days 1, 8, 15, 22, and 29. Receives: Drug: AZD3427 |
| AZD3427: Cohort 4b | Experimental | Participants with HF with EF ≥ 41% will receive SC dose B of AZD3427 on Days 1, 8, 15, 22, and 29. Receives: Drug: AZD3427 |
| AZD3427: Cohort 5b | Experimental | Participants with HFrEF will receive SC dose C of AZD3427 on Days 1, 8, 15, 22, and 29. Receives: Drug: AZD3427 |
| AZD3427: Cohort 6b | Experimental | Participants with HF with EF ≥ 41% will receive SC dose C of AZD3427 on Days 1, 8, 15, 22, and 29. Receives: Drug: AZD3427 |
| Part B: Placebo | Placebo comparator | Participants with HFrEF or HF with EF ≥ 41% will receive SC dose of placebo matched to AZD3427 on Days 1, 8, 15, 22, and 29. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing Adverse Events and Serious Adverse Events
Assessment of the safety and tolerability of single and multiple ascending doses of AZD3427.
Measured: Part A: Day 1 until Day 50 or Early termination visit (E/T); Part B: Day 1 until Day 78 or E/T
Secondary outcomes (8)
Maximum Observed Serum (peak) Drug Concentration (Cmax) of AZD3427
Evaluation of the PK of single and multiple ascending doses of AZD3427.
Measured: Part A: Day 1 (pre-dose, and 10 minutes [only for cohort 5a], 4hrs and 12hrs post-dose, and days 2, 3, 5, 8, 15, 29, and Day 50 or E/T ; Part B: Day 1 (Pre-dose and post-dose), days 8, 15, 22, and 29 (pre-dose); and days 2, 3, 32, 57, 71 and 78 or E/T
Area Under the Serum Concentration-time Curve from Zero to the Last Quantifiable Concentration (AUClast)
Evaluation of the PK of single and multiple ascending doses of AZD3427.
Measured: Part A: Day 1 (pre-dose, and 10 minutes [only for cohort 5a], 4hrs and 12hrs post-dose, and days 2, 3, 5, 8, 15, 29, and Day 50 or E/T ; Part B: Day 1 (Pre-dose and post-dose), days 8, 15, 22, and 29 (pre-dose); and days 2, 3, 32, 57, 71 and 78 or E/T
Area Under Serum Concentration-time Curve From Zero to Infinity (AUCinf)
Evaluation of the PK of single and multiple ascending doses of AZD3427.
Measured: Part A: Day 1 (pre-dose, and 10 minutes [only for cohort 5a], 4hrs and 12hrs post-dose, and days 2, 3, 5, 8, 15, 29, and Day 50 or E/T ; Part B: Day 1 (Pre-dose and post-dose), days 8, 15, 22, and 29 (pre-dose); and days 2, 3, 32, 57, 71 and 78 or E/T
Area Under the Serum Concentration-time Curve from Zero to 168 Hours Post-dose Administration (AUC0-168)
Evaluation of the PK of single and multiple ascending doses of AZD3427.
Measured: Part A: Day 1 (pre-dose, and 10 minutes [only for cohort 5a], 4hrs and 12hrs post-dose, and days 2, 3, 5, 8, 15, 29, and Day 50 or E/T ; Part B: Day 1 (Pre-dose and post-dose), days 8, 15, 22, and 29 (pre-dose); and days 2, 3, 32, 57, 71 and 78 or E/T
Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (tmax)
Evaluation of the PK of single and multiple ascending doses of AZD3427.
Measured: Part A: Day 1 (pre-dose, and 10 minutes [only for cohort 5a], 4hrs and 12hrs post-dose, and days 2, 3, 5, 8, 15, 29, and Day 50 or E/T ; Part B: Day 1 (Pre-dose and post-dose), days 8, 15, 22, and 29 (pre-dose); and days 2, 3, 32, 57, 71 and 78 or E/T
Half-life Associated with Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz)
Evaluation of the PK of single and multiple ascending doses of AZD3427.
Measured: Part A: Day 1 (pre-dose, and 10 minutes [only for cohort 5a], 4hrs and 12hrs post-dose, and days 2, 3, 5, 8, 15, 29, and Day 50 or E/T ; Part B: Day 1 (Pre-dose and post-dose), days 8, 15, 22, and 29 (pre-dose); and days 2, 3, 32, 57, 71 and 78 or E/T
Number of Participants Testing Positive for the Presence of Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb) to AZD3427
Evaluation of the immunogenicity of single and multiple ascending doses of AZD3427.
Measured: Part A: Day 1 (pre-dose), Days 15, 29, and 50 or E/T; Part B: Days 1, 15, 29 (Pre-dose), Days 57 and 78 or E/T
Evaluation of Positive Anti-drug Antibodies Titer
Evaluation of the immunogenicity of single and multiple ascending doses of AZD3427.
Measured: Part A: Day 1 (pre-dose), Days 15, 29, and 50 or E/T; Part B: Days 1, 15, 29 (Pre-dose), Days 57 and 78 or E/T
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2020
- Study start17 Nov 2020
- Primary completion14 Sep 2022
- Study completion14 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ronald Goldwater, MD, Principal investigator, Parexel Early Phase Clinical Unit (Baltimore), Harbor Hospital, 3001 S. Hanover St., Baltimore, MD 21225, United States of America (USA)David Lanfear, MD, Principal investigator, Henry Ford Hospital, USA, MI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04630067
- Sponsor's protocol ID
- D8330C00001
- Status last verified
- Oct 2022
- First submitted
- 27 Oct 2020
- Last updated
- 20 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Publications
Connolly K, George R, Omar S, Matsson E, Astrand M, Althage M, Pettersen D, Mohamed E, Fang K, Lima JAC, Kujacic M, Odesjo H, Turton M, Johannesson P, Gabrielsen A, Ufnal M. Novel Relaxin Receptor RXFP1 Agonist AZD3427 in the Treatment of Heart Failure: A Phase 1a/b, First-in-Human, Randomized, Single-Blind, Placebo-Controlled Study. J Am Heart Assoc. 2024 Aug 6;13(15):e034067. doi: 10.1161/JAHA.123.034067. Epub 2024 Jul 26.
PubMed 39056338
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ia/b Randomized, Single-blinded, Placebo-controlled Study to Evaluate the Safety, Tolerability, Immunogenicity, and Pharmacokinetics of Single Ascending Doses of AZD3427 in Healthy Volunteers and Multiple Ascending Doses of AZD3427 in Patients With Heart Failure (HFrEF and HF With EF ≥ 41%)
- ClinicalTrials.gov ID
- NCT04630067
- Acronym / sponsor ID
- D8330C00001
- Conditions
- Heart Failure
- Keywords
- Heart failure with reduced ejection fraction, Heart failure with ejection fraction of ≥ 41%, AZD3427, First-time-in-human
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 17 Nov 2020 (actual)
- Primary completion
- 14 Sep 2022 (actual)
- Study completion
- 14 Sep 2022 (actual)
- First posted
- 16 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This first-time-in-human (FTIH) study will be conducted to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of single doses of AZD3427 in healthy volunteers and multiple doses of AZD3427 in patients with heart failure (HF).
Detailed description
This is a multi-center single and multiple ascending dose study (SAD and MAD).
Part A (SAD) will include 7 cohorts (8 healthy volunteers in each cohort) and will randomize to AZD3427 or placebo, in a 6:2 ratio. One cohort will entirely include participants of Japanese descent.
Part B (MAD) will include 6 cohorts (8 heart failure patients in each cohort) and will randomize to AZD3427 or placebo in a 6:2 ratio. Of these, 3 cohorts will contain participants with heart failure with reduced ejection fraction [HFrEF] and the other 3 cohorts will comprise of participants with heart failure with HF with ejection fraction (EF) ≥ 41%. There will be a maximum screening period of 27 days. Participants in part A and B will undergo study drug administration on Day 1. In addition, participants in part B will return for 4 additional doses on Days 8, 15, 22, and 29. Participants will be followed for at least 50 days after the last dose of study drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 15
| Arm | Type | Receives |
|---|---|---|
| AZD3427: Cohort 1a | Experimental | Drug: AZD3427Participants will receive single SC dose A of AZD3427 on Day 1. |
| AZD3427: Cohort 2a | Experimental | Drug: AZD3427Participants will receive single SC dose B of AZD3427 on Day 1. |
| AZD3427: Cohort 3a | Experimental | Drug: AZD3427Participants will receive single SC dose C of AZD3427 on Day 1. |
| AZD3427: Cohort 4a | Experimental | Drug: AZD3427Participants will receive single SC dose D of AZD3427 on Day 1. |
| AZD3427: Cohort 5a | Experimental | Drug: AZD3427Participants will receive single IV dose E of AZD3427 on Day 1. |
| AZD3427: Cohort 6a | Experimental | Drug: AZD3427Participants of Japanese descent will receive single SC dose anticipated equal to the highest dose of AZD3427 in the global cohorts on Day 1. |
| AZD3427: Cohort 7a | Experimental | Drug: AZD3427Participants will receive single SC dose F of AZD3427 on Day 1 |
| Part A: Placebo | Placebo comparator | Drug: PlaceboParticipants will receive single SC or IV dose of placebo matched to AZD3427 on Day 1. |
| AZD3427: Cohort 1b | Experimental | Drug: AZD3427Participants with HFrEF will receive SC dose A of AZD3427 on Days 1, 8, 15, 22, and 29. |
| AZD3427: Cohort 2b | Experimental | Drug: AZD3427Participants with HF with EF ≥ 41% will receive SC dose A of AZD3427 on Days 1, 8, 15, 22, and 29. |
| AZD3427: Cohort 3b | Experimental | Drug: AZD3427Participants with HFrEF will receive SC dose B of AZD3427 on Days 1, 8, 15, 22, and 29. |
| AZD3427: Cohort 4b | Experimental | Drug: AZD3427Participants with HF with EF ≥ 41% will receive SC dose B of AZD3427 on Days 1, 8, 15, 22, and 29. |
| AZD3427: Cohort 5b | Experimental | Drug: AZD3427Participants with HFrEF will receive SC dose C of AZD3427 on Days 1, 8, 15, 22, and 29. |
| AZD3427: Cohort 6b | Experimental | Drug: AZD3427Participants with HF with EF ≥ 41% will receive SC dose C of AZD3427 on Days 1, 8, 15, 22, and 29. |
| Part B: Placebo | Placebo comparator | Drug: PlaceboParticipants with HFrEF or HF with EF ≥ 41% will receive SC dose of placebo matched to AZD3427 on Days 1, 8, 15, 22, and 29. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Part A will include healthy men and non-pregnant, non-lactating females of non-childbearing potential with a body mass index (BMI) of 18-30 kg/m^2 and a weight of 55-100 kg. One cohort will require participants be of Japanese descent
- Part B will include men and non-pregnant, non-lactating females of non-childbearing potential
- Participants have a BMI of 18-40 kg/m^2 and a weight of 55-136 kg
- Participants with a diagnosis of stage C HF New York Heart Association (NYHA) Class I-III on stable medical therapy for at least 12 weeks
- Participants with diagnosis of HFrEF will be defined as those with EF ≤ 40% and HF with EF ≥ 41%
Key exclusion criteria (37 listed)
- Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of study drug or planned surgical procedure before study completion
- History of vascular and left ventricular aneurysms or prior dissections
- Any history of joint hypermobility, Marfan's syndrome, or any connective tissue disorder
- Clinical signs and symptoms consistent with Coronavirus disease-19 or confirmed infection within the last 4 weeks
- History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity injection devices or to drugs with a similar chemical structure or class to AZD3427 or any component of AZD3427
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD3427Participants will receive SC or IV dose of AZD3427 as per the arm they are randomized. | Drug | AZD3427: Cohort 1a, AZD3427: Cohort 1b, AZD3427: Cohort 2a, AZD3427: Cohort 2b, AZD3427: Cohort 3a, AZD3427: Cohort 3b, AZD3427: Cohort 4a, AZD3427: Cohort 4b, AZD3427: Cohort 5a, AZD3427: Cohort 5b, AZD3427: Cohort 6a, AZD3427: Cohort 6b, AZD3427: Cohort 7a |
| PlaceboParticipants will receive SC or IV dose of placebo matched to AZD3427 as per the arm they are randomized. | Drug | Part A: Placebo, Part B: Placebo |
Primary outcome
Number of Participants Experiencing Adverse Events and Serious Adverse Events
Time frame: Part A: Day 1 until Day 50 or Early termination visit (E/T); Part B: Day 1 until Day 78 or E/T
Assessment of the safety and tolerability of single and multiple ascending doses of AZD3427.
8 secondary outcomes
Maximum Observed Serum (peak) Drug Concentration (Cmax) of AZD3427
Time frame: Part A: Day 1 (pre-dose, and 10 minutes [only for cohort 5a], 4hrs and 12hrs post-dose, and days 2, 3, 5, 8, 15, 29, and Day 50 or E/T ; Part B: Day 1 (Pre-dose and post-dose), days 8, 15, 22, and 29 (pre-dose); and days 2, 3, 32, 57, 71 and 78 or E/T
Area Under the Serum Concentration-time Curve from Zero to the Last Quantifiable Concentration (AUClast)
Time frame: Part A: Day 1 (pre-dose, and 10 minutes [only for cohort 5a], 4hrs and 12hrs post-dose, and days 2, 3, 5, 8, 15, 29, and Day 50 or E/T ; Part B: Day 1 (Pre-dose and post-dose), days 8, 15, 22, and 29 (pre-dose); and days 2, 3, 32, 57, 71 and 78 or E/T
Area Under Serum Concentration-time Curve From Zero to Infinity (AUCinf)
Time frame: Part A: Day 1 (pre-dose, and 10 minutes [only for cohort 5a], 4hrs and 12hrs post-dose, and days 2, 3, 5, 8, 15, 29, and Day 50 or E/T ; Part B: Day 1 (Pre-dose and post-dose), days 8, 15, 22, and 29 (pre-dose); and days 2, 3, 32, 57, 71 and 78 or E/T
Area Under the Serum Concentration-time Curve from Zero to 168 Hours Post-dose Administration (AUC0-168)
Time frame: Part A: Day 1 (pre-dose, and 10 minutes [only for cohort 5a], 4hrs and 12hrs post-dose, and days 2, 3, 5, 8, 15, 29, and Day 50 or E/T ; Part B: Day 1 (Pre-dose and post-dose), days 8, 15, 22, and 29 (pre-dose); and days 2, 3, 32, 57, 71 and 78 or E/T
Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (tmax)
Time frame: Part A: Day 1 (pre-dose, and 10 minutes [only for cohort 5a], 4hrs and 12hrs post-dose, and days 2, 3, 5, 8, 15, 29, and Day 50 or E/T ; Part B: Day 1 (Pre-dose and post-dose), days 8, 15, 22, and 29 (pre-dose); and days 2, 3, 32, 57, 71 and 78 or E/T
Half-life Associated with Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz)
Time frame: Part A: Day 1 (pre-dose, and 10 minutes [only for cohort 5a], 4hrs and 12hrs post-dose, and days 2, 3, 5, 8, 15, 29, and Day 50 or E/T ; Part B: Day 1 (Pre-dose and post-dose), days 8, 15, 22, and 29 (pre-dose); and days 2, 3, 32, 57, 71 and 78 or E/T
Number of Participants Testing Positive for the Presence of Anti-drug Antibodies (ADA) and Neutralizing Antibodies (NAb) to AZD3427
Time frame: Part A: Day 1 (pre-dose), Days 15, 29, and 50 or E/T; Part B: Days 1, 15, 29 (Pre-dose), Days 57 and 78 or E/T
Evaluation of Positive Anti-drug Antibodies Titer
Time frame: Part A: Day 1 (pre-dose), Days 15, 29, and 50 or E/T; Part B: Days 1, 15, 29 (Pre-dose), Days 57 and 78 or E/T
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2022.
- Derived from this study: PubMed 39056338Connolly K, George R, Omar S, Matsson E, Astrand M, Althage M, Pettersen D, Mohamed E, Fang K, Lima JAC, Kujacic M, Odesjo H, Turton M, Johannesson P, Gabrielsen A, Ufnal M. Novel Relaxin Receptor RXFP1 Agonist AZD3427 in the Treatment of Heart Failure: A Phase 1a/b, First-in-Human, Randomized, Single-Blind, Placebo-Controlled Study. J Am Heart Assoc. 2024 Aug 6;13(15):e034067. doi: 10.1161/JAHA.123.034067. Epub 2024 Jul 26.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ronald Goldwater, MD principal investigator
Parexel Early Phase Clinical Unit (Baltimore), Harbor Hospital, 3001 S. Hanover St., Baltimore, MD 21225, United States of America (USA)
David Lanfear, MD principal investigator
Henry Ford Hospital, USA, MI
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD3427 in people with Heart Failure, run by AstraZeneca at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Experiencing Adverse Events and Serious Adverse Events (time frame: Part A: Day 1 until Day 50 or Early termination visit (E/T); Part B: Day 1 until Day 78 or E/T). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04630067, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2022.