ENDURE: A Randomized, Open-label, Dose-ranging Study in Adults and Pediatric Individuals ≥ 12 Years of Age to Assess the Safety, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AZD7442, for Pre-exposure Prophylaxis of COVID-19

Sponsor

AstraZeneca (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05375760

Collaborator

(none)

200

Enrollment

Locations

Arms

25.5

Anticipated Duration (Months)

12.5

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Phase II Randomized, Open-label, Multicenter, Dose-ranging Study in Adults and Pediatric Individuals ≥ 12 years of Age to Assess the Safety, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AZD7442, a Combination Product of Two Monoclonal Antibodies (Tixagevimab and Cilgavimab), for Pre-exposure Prophylaxis of COVID-19

Condition or Disease	Intervention/Treatment	Phase
Coronavirus Disease 2019 (COVID-19)	Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061]) Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061])	Phase 2

Detailed Description

AZD7442, a combination of 2 monoclonal antibodies (tixagevimab [investigational name, AZD8895] and cilgavimab [investigational name, AZD1061]), is being developed for the prophylaxis and treatment of coronavirus disease 2019 (COVID-19).

This Phase II dose-ranging study will investigate the safety, immunogenicity, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of AZD7442 repeat dosing regimens for preexposure prophylaxis of COVID-19 in adults and pediatric individuals (≥ 12 years of age weighing at least 40 kg), who are moderately to severely immunocompromised.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

A Phase II Randomized, Open-label, Multicenter, Dose-ranging Study in Adults and Pediatric Individuals ≥ 12 Years of Age to Assess the Safety, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AZD7442, a Combination Product of Two Monoclonal Antibodies (Tixagevimab and Cilgavimab), for Pre-exposure Prophylaxis of COVID-19

Actual Study Start Date :

Jun 9, 2022

Anticipated Primary Completion Date :

Nov 15, 2023

Anticipated Study Completion Date :

Jul 24, 2024

Arms and Interventions

Arm	Intervention/Treatment
Other: Arm A 600 mg AZD7442 following 300 mg AZD7442 every 3 months (5 doses totally)	Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061]) Arm A - Day 1: 600 mg AZD7442 administered sequentially as a 3 mL IM injection containing 300 mg tixagevimab (AZD8895) and a 3 mL IM injection containing 300 mg cilgavimab (AZD1061), one injection in each gluteal region. Arm A - Days 92, 183, 274, 365: 300 mg AZD7442 administered sequentially as a 1.5 mL IM injection containing 150 mg tixagevimab (AZD8895) and a 1.5 mL IM injection containing 150 mg cilgavimab (AZD1061), one injection in each gluteal region.
Other: Arm B 1200mg AZD7442 following 600 mg AZD7442 every 6 months (3 doses totally)	Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061]) Arm B - Day 1: 1200 mg AZD7442 (600 mg tixagevimab [AZD8895] and 600 mg cilgavimab [AZD1061]) administered by IV infusion. Arm B - Days 183, 365: 600 mg AZD7442 administered sequentially as a 3 mL IM injection containing 300 mg tixagevimab (AZD8895) and a 3 mL IM injection containing 300 mg cilgavimab (AZD1061), one injection in each gluteal region.

Arm

Intervention/Treatment

Other: Arm A

600 mg AZD7442 following 300 mg AZD7442 every 3 months (5 doses totally)

Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061])

Arm A - Day 1: 600 mg AZD7442 administered sequentially as a 3 mL IM injection containing 300 mg tixagevimab (AZD8895) and a 3 mL IM injection containing 300 mg cilgavimab (AZD1061), one injection in each gluteal region. Arm A - Days 92, 183, 274, 365: 300 mg AZD7442 administered sequentially as a 1.5 mL IM injection containing 150 mg tixagevimab (AZD8895) and a 1.5 mL IM injection containing 150 mg cilgavimab (AZD1061), one injection in each gluteal region.

Other: Arm B

1200mg AZD7442 following 600 mg AZD7442 every 6 months (3 doses totally)

Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061])

Arm B - Day 1: 1200 mg AZD7442 (600 mg tixagevimab [AZD8895] and 600 mg cilgavimab [AZD1061]) administered by IV infusion. Arm B - Days 183, 365: 600 mg AZD7442 administered sequentially as a 3 mL IM injection containing 300 mg tixagevimab (AZD8895) and a 3 mL IM injection containing 300 mg cilgavimab (AZD1061), one injection in each gluteal region.

Outcome Measures

Primary Outcome Measures

Adverse Events [2 years]
To evaluate the safety and tolerability of AZD7442
Serious Adverse Events [2 years]
To evaluate the safety and tolerability of AZD7442
Adverse Events of Special Interest [2 years]
To evaluate the safety and tolerability of AZD7442
Incidence of ADA in serum [15 months]
To evaluate the immunogenicity of AZD7442

Secondary Outcome Measures

Serum AZD7442 concentrations [15 months]
To evaluate the PK of AZD7442 in serum
Changes from baseline in GMTs and GMFRs values in SARS-CoV-2 nAbs [15 months]
To determine anti-SARS-CoV-2 nAb levels in serum after administration of AZD7442

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. For pediatric participants: informed assent is to be provided by the participant; informed consent must be provided by the participant's legal guardian
Ensure that participants who are considered by the Investigator clinically unable to consent at screening and who are entered into the study by the consent of a legally acceptable representative show evidence of assent, as applicable in accordance with local regulations.
Participant must be an adult (≥ 18 years of age) or pediatric individual (≥ 12 to < 18 years of age weighing ≥ 40 kg) at the time of signing the ICF or assent (for pediatric participants).

Exclusion Criteria:

Any clinical signs and symptoms consistent with COVID-19, eg, fever, dry cough, dyspnea, sore throat, fatigue for ≥ 5 days or confirmed COVID-19 infection by appropriate laboratory test within 28 days prior to screening.
History or current hospitalization for worsening disease during the one month prior to screening, with no change in condition at the time of study enrollment as judged by the Investigator.
Current need for hospitalization or immediate medical attention in a clinic or emergency room service in the clinical opinion of the Investigator.
Previous hypersensitivity, infusion-related reaction, or severe adverse reaction following administration of a mAb.
Known history of allergy to any component of the IMP formulation.
History of clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IV infusions or venepuncture.
Any other significant disease, disorder, or finding that may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study, or impair interpretation of the study data
Any co-morbidity requiring surgery within 7 days prior to study entry, or that is considered life-threatening in the opinion of the Investigator within 30 days prior to study entry.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35215
2	Research Site	Little Rock	Arkansas	United States	72205
3	Research Site	Modesto	California	United States	95350
4	Research Site	Westminster	California	United States	92683
5	Research Site	Wheat Ridge	Colorado	United States	80033
6	Research Site	Hollywood	Florida	United States	33024
7	Research Site	Miami	Florida	United States	33125
8	Research Site	Wesley Chapel	Florida	United States	33545
9	Research Site	West Palm Beach	Florida	United States	33409
10	Research Site	Saint Louis	Missouri	United States	63141
11	Research Site	Endicott	New York	United States	13760
12	Research Site	Austin	Texas	United States	78745
13	Research Site	El Paso	Texas	United States	79925
14	Research Site	Annandale	Virginia	United States	22003
15	Research Site	Leeds		United Kingdom	LS9 7TF
16	Research Site	Manchester		United Kingdom	M8 5RB

Sponsors and Collaborators

AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

AstraZeneca

ClinicalTrials.gov Identifier:

NCT05375760

Other Study ID Numbers:

D8850C00010
2022-001014-20

First Posted:

May 17, 2022

Last Update Posted:

Jul 20, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by AstraZeneca

ENDURE

Additional relevant MeSH terms:

COVID-19

Study Results

No Results Posted as of Jul 20, 2022