NCT04630067

Brief 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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
105

participants targeted

Target at P75+ for phase_1 heart-failure

Timeline
Completed

Started Nov 2020

Geographic Reach
1 country

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 27, 2020

Completed
20 days until next milestone

First Posted

Study publicly available on registry

November 16, 2020

Completed
1 day until next milestone

Study Start

First participant enrolled

November 17, 2020

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 14, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 14, 2022

Completed
Last Updated

October 20, 2022

Status Verified

October 1, 2022

Enrollment Period

1.8 years

First QC Date

October 27, 2020

Last Update Submit

October 19, 2022

Conditions

Heart Failure

Keywords

Heart failure with reduced ejection fractionHeart failure with ejection fraction of ≥ 41%AZD3427First-time-in-human

Outcome Measures

Primary Outcomes (1)

  • Number of Participants Experiencing Adverse Events and Serious Adverse Events

    Assessment of the safety and tolerability of single and multiple ascending doses of AZD3427.

    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

    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)

    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)

    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)

    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)

    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

  • +3 more secondary outcomes

Study Arms (15)

AZD3427: Cohort 1a

EXPERIMENTAL

Participants will receive single SC dose A of AZD3427 on Day 1.

Drug: AZD3427

AZD3427: Cohort 2a

EXPERIMENTAL

Participants will receive single SC dose B of AZD3427 on Day 1.

Drug: AZD3427

AZD3427: Cohort 3a

EXPERIMENTAL

Participants will receive single SC dose C of AZD3427 on Day 1.

Drug: AZD3427

AZD3427: Cohort 4a

EXPERIMENTAL

Participants will receive single SC dose D of AZD3427 on Day 1.

Drug: AZD3427

AZD3427: Cohort 5a

EXPERIMENTAL

Participants will receive single IV dose E of AZD3427 on Day 1.

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.

Drug: AZD3427

AZD3427: Cohort 7a

EXPERIMENTAL

Participants will receive single SC dose F of AZD3427 on Day 1

Drug: AZD3427

Part A: Placebo

PLACEBO COMPARATOR

Participants will receive single SC or IV dose of placebo matched to AZD3427 on Day 1.

Drug: Placebo

AZD3427: Cohort 1b

EXPERIMENTAL

Participants with HFrEF will receive SC dose A of AZD3427 on Days 1, 8, 15, 22, and 29.

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.

Drug: AZD3427

AZD3427: Cohort 3b

EXPERIMENTAL

Participants with HFrEF will receive SC dose B of AZD3427 on Days 1, 8, 15, 22, and 29.

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.

Drug: AZD3427

AZD3427: Cohort 5b

EXPERIMENTAL

Participants with HFrEF will receive SC dose C of AZD3427 on Days 1, 8, 15, 22, and 29.

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.

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.

Drug: Placebo

Interventions

AZD3427DRUG

Participants will receive SC or IV dose of AZD3427 as per the arm they are randomized.

AZD3427: Cohort 1aAZD3427: Cohort 1bAZD3427: Cohort 2aAZD3427: Cohort 2bAZD3427: Cohort 3aAZD3427: Cohort 3bAZD3427: Cohort 4aAZD3427: Cohort 4bAZD3427: Cohort 5aAZD3427: Cohort 5bAZD3427: Cohort 6aAZD3427: Cohort 6bAZD3427: Cohort 7a
PlaceboDRUG

Participants will receive SC or IV dose of placebo matched to AZD3427 as per the arm they are randomized.

Part A: PlaceboPart B: Placebo

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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
  • 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
  • +22 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Research Site

Little Rock, Arkansas, 72204, United States

Location

Research Site

Glendale, California, 91206, United States

Location

Research Site

Daytona Beach, Florida, 32117, United States

Location

Research Site

Doral, Florida, 33166, United States

Location

Research Site

Hallandale, Florida, 33009, United States

Location

Research Site

Jacksonville, Florida, 32216, United States

Location

Research Site

Owensboro, Kentucky, 42303, United States

Location

Research Site

Brooklyn, Maryland, 21225, United States

Location

Research Site

Detroit, Michigan, 48202, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Related Publications (1)

  • 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.

    PMID: 39056338DERIVED

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular Diseases

Study Officials

  • Ronald Goldwater, MD

    Parexel Early Phase Clinical Unit (Baltimore), Harbor Hospital, 3001 S. Hanover St., Baltimore, MD 21225, United States of America (USA)

    PRINCIPAL INVESTIGATOR

  • David Lanfear, MD

    Henry Ford Hospital, USA, MI

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 27, 2020

First Posted

November 16, 2020

Study Start

November 17, 2020

Primary Completion

September 14, 2022

Study Completion

September 14, 2022

Last Updated

October 20, 2022

Record last verified: 2022-10

Data Sharing

IPD Sharing
Will share

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.

Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
More information

Locations

US(10)