Investigation of the Effects of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of Opemalirsen (AZD2373)

NCT07154901 | Recruiting Phase 1 FDA Drug

• 1 other identifier: D6800C00006
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

This study is being conducted to investigate the PK, safety, and tolerability of opemalirsen in participants with renal impairment, compared to participants with normal renal function.

Conditions

Renal Impairment

Keywords

Renal impairment; AZD2373; Pharmacokinetics; Severe; Mild; Moderate; Matched Healthy Controls; opemalirsen

Outcome Measures

Primary Outcomes (3)

• AUCinf

  Area under the concentration-time curve from zero to infinity

  Pre-dose to 3 weeks post dose

• AUClast

  Area under the concentration-time curve from zero to the last measurable concentration

  Pre-dose to 3 weeks post-dose

• Cmax

  Maximum observed plasma concentration

  Pre-dose to 3 weeks post-dose

Secondary Outcomes (8)

• Tmax

  Pre-dose to 3 weeks post-dose

• t1/2λz

  Pre-dose to 3 weeks post-dose

• CL/F

  Pre-dose to 3 weeks post-dose

• Vz/F

  Pre-dose to 3 weeks post-dose

• Fu

  Pre-dose to 3 weeks post-dose

Other Outcomes (1)

• Number of Participants with Abnormal AEs and SAEs

  Screening to Day 57

Study Arms (4)

Group 1

EXPERIMENTAL

Healthy participants will receive a single subcutaneous injection of AZD2373.

Drug: Opemalirsen (AZD2373)

Group 2

EXPERIMENTAL

Severe renal impairment participants will receive a single subcutaneous injection of AZD2373.

Drug: Opemalirsen (AZD2373)

Group 3

EXPERIMENTAL

Moderate renal impairment participants will receive a single subcutaneous injection of AZD2373

Drug: Opemalirsen (AZD2373)

Group 4

EXPERIMENTAL

Mild renal impairment participants will receive a single subcutaneous injection of AZD2373

Drug: Opemalirsen (AZD2373)

Interventions

Opemalirsen (AZD2373) DRUG

Single, subcutaneous injection of AZD2373

Group 1; Group 2; Group 3; Group 4

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Age
• Participant must be 18 to 80 years of age, inclusive, at the time of signing the informed consent. Type of Participant and Disease Characteristics For all participants, BSA-adjusted eGFR will be determined by the local laboratory, calculated based on serum creatinine using the CKD-EPI equation (see Section 4.1).
• Healthy matched control participants only (Group 1):
• Participant must be medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, or 12-lead ECGs, as deemed by the investigator at screening and Day -1.
• Have an eGFR of ≥ 90 mL/min determined at screening.
• Participants with renal impairment only (Group 2 and optional Groups 3 and 4):
• Diagnosis of chronic kidney disease with stable renal function in the 3 months prior to dosing, as determined by the investigator, based on medical history or eGFR, and not requiring dialysis. 5 Participants with renal impairment, as follows, based on CKD-EPI equation (BSA-adjusted eGFR) at screening:
• Group 2: have severe renal impairment (eGFR \< 30 mL/min), not requiring dialysis.
• Group 3 (optional): have moderate renal impairment (eGFR ≥ 30 to \< 60 mL/min)
• Group 4 (optional): have mild renal impairment (eGFR ≥ 60 to \< 90 mL/min) 6 Participants on angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta-blocker, diuretics, or on any other cardiorenal relevant treatment should be on a stable dose for at least 2 weeks prior to screening. Weight 7 Body weight of at least 50 kg and body mass index (BMI) within the range 18 to 40 kg/m2 (inclusive). Sex and Contraceptive/Barrier Requirements 8 Male and/or female, assigned at birth, inclusive of all gender identities. 9 Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• (a) Male participants must agree to the following contraception guidance for the duration of the study (from the time of study intervention administration) until 3 months after discharge: (i) Non-sterilised male participants should avoid fathering a child by either true abstinence or by using (together with their female partner/spouse) a highly effective contraception form of birth control in combination with a barrier method, starting from the time of study intervention administration until 3 months after discharge. Acceptable methods of preventing pregnancy include birth control pills, injections, implants, or patches, IUDs, tubal ligation/occlusion, and vasectomy. (ii) Male participants who have been sterilised are required to use one barrier method of contraception (condom) from the time of study intervention administration until after discharge. A barrier method is not necessary if the female partner is sterilised. (iii) Male participants should not donate sperm from the time of study intervention administration until 3 months after discharge. (b) Female participants: must not be pregnant and must have a negative pregnancy test at screening (all female participants) and check-in (WOCBP) and must not be lactating.
• Women of Childbearing Potential (WOCBP): A woman is considered of childbearing potential if she is capable of conceiving. While this is typically the case following menarche and up until she becomes post-menopausal, adolescents can ovulate prior to first menarche, and women with irregular menses may also be fertile. Women Not of Childbearing Potential (WNOCBP): Females not of childbearing potential are defined as females who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are post-menopausal. Females will be considered post-menopausal if they have been amenorrhoeic for 12 months prior to the planned date of dose administration without an alternative medical cause. The following age-specific requirements apply:
• Females \< 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone levels in the postmenopausal range.
• Females ≥ 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment. (i) Female participants should be stable on the chosen method of contraception for a minimum of 3 months before entering the study. (ii) Female participants of childbearing potential must use one highly effective form of birth control. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly. Females of childbearing potential who are sexually active with a non-sterilised male partner must agree to use one highly effective method of birth control, as defined below, throughout the study and until at least 3 months after discharge. Cessation of contraception after this point should be discussed with a responsible physician. Note: contraception is not required for female participants of non-childbearing potential.

You may not qualify if:

• Medical Conditions
• All participants:
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the investigator, at screening or Day -1, or history of hypersensitivity to drugs with a similar chemical structure or class to opemalirsen.
• History of any major surgical procedure within 30 days prior to study intervention.
• Judgement by the investigator that the participant should not participate in the study if they have any ongoing or recent (ie, during the screening period) minor medical complaints that may interfere with the interpretation of study data or if they are considered unlikely to comply with study procedures, restrictions, and requirements.
• Liver disease (non-alcoholic and alcoholic steatohepatitis; drug-induced, viral, or autoimmune hepatitis; primary biliary cirrhosis; primary sclerosing cholangitis; hemochromatosis; alpha-1 antitrypsin deficiency; Wilson's disease) including positive results for hepatitis B surface antigen, hepatitis B core antibody or hepatitis C virus antibody.
• History of cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy, or variceal bleeding.
• QTcF \> 470 ms in participants without bundle branch block and \> 480 ms in participants with bundle branch block.
• Any of the following out of range laboratory values:
• ALT or AST \> 1.5 × ULN
• INR \> 1.2, unless related to therapeutic anticoagulation
• APTT ≥ 1.3 × normal, unless related to therapeutic anticoagulation
• HbA1c ≥ 10%
• Positive test for human immunodeficiency virus at screening.
• Known history of drug or alcohol abuse within 1 year of screening.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Research Site

Miami, Florida, 33172, United States

RECRUITING

Research Site

Orlando, Florida, 32808, United States

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be assigned to the following groups based on BSA-adjusted eGFR at screening using the creatinine-based CKD-EPI (2021) race-free estimation of eGFR: * Part 1: * Group 1: Participants with normal renal function (eGFR ≥ 90 mL/min; n = 8 to 20 participants) * Group 2: Participants with severe renal impairment not on dialysis (eGFR \< 30 mL/min; n = 8 to 10 participants) * Part 2 (Optional): * Group 3: Participants with moderate renal impairment (eGFR ≥ 30 mL/min to \< 60 mL/min; n = 8 to 10 participants) * Group 4: Participants with mild renal impairment (eGFR ≥ 60 mL/min to \< 90 mL/min; n = 8 to 10 participants)

Study Record Dates

• First Submitted: July 28, 2025
• First Posted: September 4, 2025
• Study Start: August 18, 2025
• Primary Completion (Estimated): June 15, 2026
• Study Completion (Estimated): June 15, 2026
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• 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 deidentified 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.

Locations

US (2)