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NCT05375760: 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

Terminated Phase 2 Results posted Last updated 23 October 2024
What this trial tests

Phase 2 trial testing AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061]) in Coronavirus Disease 2019 (COVID-19) in 251 participants. Terminated before completion.

Timeline
9 June 2022
Primary endpoint
4 October 2023
4 October 2023

Quick facts

Lead sponsorAstraZeneca
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposeprevention
Enrollment251
Start date9 June 2022
Primary completion4 October 2023
Estimated completion4 October 2023
Sites16 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

12 and older, any sex, with Coronavirus Disease 2019 (COVID-19). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

AEs, SAEs, and AESIs Primary · Safety data were recorded from the time of the first IMP administration throughout the study for an average safety follow up time of 48.85 weeks. This was shorter than the planned one of 105 weeks due to FDA's request to halt dosing.

To evaluate the safety and tolerability of AZD7442

Adverse Events
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M84
AZD7442: 1200 mg ONCE / 600mg Q6M66
Serious Adverse Events
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M13
AZD7442: 1200 mg ONCE / 600mg Q6M10
Adverse Events of Special Interest
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M9
AZD7442: 1200 mg ONCE / 600mg Q6M7
ADA in Serum Responses Primary · Serum ADA were assessed through the treatment period at the specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365, 456 days or early discontinuation visit after the first IMP administration.

To evaluate the immunogenicity of AZD7442

GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M1
AZD7442: 1200 mg ONCE / 600mg Q6M3
Serum AZD7442 Concentrations Secondary · Serum PK was assessed through the treatment period at the specific timepoints: day 1 post-dose (600mg Q6M arm only), 3, 11, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early discontinuation visit after the first IMP administration.

To evaluate the PK of AZD7442 in serum

Day 1, Post-dose
GroupValue95% CI
AZD7442: 1200 mg ONCE / 600mg Q6M285.8539± 176.0959
Day 3
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M30.0089± 83.7707
AZD7442: 1200 mg ONCE / 600mg Q6M165.1457± 196.9756
Day 11
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M45.5626± 53.9503
AZD7442: 1200 mg ONCE / 600mg Q6M123.2505± 160.5606
Day 29
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M40.0381± 48.7457
AZD7442: 1200 mg ONCE / 600mg Q6M105.8292± 76.5535
Day 92
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M27.9754± 48.9241
AZD7442: 1200 mg ONCE / 600mg Q6M63.0711± 76.0487
Day 121
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M42.1820± 53.2624
Day 183
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M23.8985± 58.4175
AZD7442: 1200 mg ONCE / 600mg Q6M26.4300± 85.1380
Day 212
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M36.5360± 54.5622
AZD7442: 1200 mg ONCE / 600mg Q6M60.5211± 44.6566
Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay) Secondary · SARSCoV-2 nAbs (Wild Type Assay) were assessed through the treatment period at these specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early termination visit after the first IMP administration.

To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442

Baseline Titer
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M203.5± 6.43
AZD7442: 1200 mg ONCE / 600mg Q6M198.9± 7.70
Day 29 Titer
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M1442.8± 1.88
AZD7442: 1200 mg ONCE / 600mg Q6M3497.1± 2.10
Day 92 Titer
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M1052.5± 2.22
AZD7442: 1200 mg ONCE / 600mg Q6M2268.6± 2.30
Day 121 Titer
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M1520.2± 1.97
Day 183 Titer
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M1209.8± 1.95
AZD7442: 1200 mg ONCE / 600mg Q6M1337.9± 2.10
Day 212 Titer
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M941.2± 2.08
AZD7442: 1200 mg ONCE / 600mg Q6M1436.1± 1.78
Day 274 Titer
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M488.5± 2.38
AZD7442: 1200 mg ONCE / 600mg Q6M864.7± 1.98
Day 365 Titer
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M482.1± 1.21
AZD7442: 1200 mg ONCE / 600mg Q6M578.9± 2.21
Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) Secondary · SARSCoV-2 nAbs (Pseudo Neutralization Assay) were assessed through the study at these specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early termination visit after the first IMP administration.

To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442

Baseline Titer
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M1613.3± 7.96
AZD7442: 1200 mg ONCE / 600mg Q6M1735.8± 8.35
Day 29 Titer
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M32170.5± 1.86
AZD7442: 1200 mg ONCE / 600mg Q6M111726.8± 1.75
Day 92 Titer
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M13940.9± 1.88
AZD7442: 1200 mg ONCE / 600mg Q6M38048.0± 1.73
Day 121 Titer
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M23177.5± 1.87
Day 183 Titer
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M12018.5± 1.75
AZD7442: 1200 mg ONCE / 600mg Q6M15554.6± 1.80
Day 212 Titer
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M19353.3± 1.72
AZD7442: 1200 mg ONCE / 600mg Q6M36519.3± 1.67
Day 274 Titer
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M12816.8± 1.93
AZD7442: 1200 mg ONCE / 600mg Q6M23583.5± 1.91
Day 365 Titer
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M5068.4± 1.55
AZD7442: 1200 mg ONCE / 600mg Q6M7155.4± 2.01
Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Wild-type Assay) Secondary · SARSCoV-2 nAbs (Wild Type Assay) were assessed through the treatment period at these specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early termination visit after the first IMP administration.

To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442

Day 29 fold rise
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M6.87± 4.765
AZD7442: 1200 mg ONCE / 600mg Q6M16.79± 6.429
Day 92 fold rise
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M4.32± 4.329
AZD7442: 1200 mg ONCE / 600mg Q6M10.53± 6.362
Day 121 fold rise
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M6.53± 4.928
Day 183 fold rise
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M5.29± 4.744
AZD7442: 1200 mg ONCE / 600mg Q6M5.43± 5.122
Day 212 fold rise
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M4.09± 5.554
AZD7442: 1200 mg ONCE / 600mg Q6M5.28± 6.243
Day 274 fold rise
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M1.96± 4.385
AZD7442: 1200 mg ONCE / 600mg Q6M3.08± 5.820
Day 365 fold rise
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M9.97± 1.093
AZD7442: 1200 mg ONCE / 600mg Q6M2.00± 5.343
Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) Secondary · SARSCoV-2 nAbs (Pseudo Neutralization Assay) were assessed through the study at these specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early termination visit after the first IMP administration.

To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442

Day 29 fold rise
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M18.02± 7.081
AZD7442: 1200 mg ONCE / 600mg Q6M58.84± 8.473
Day 92 fold rise
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M7.82± 7.270
AZD7442: 1200 mg ONCE / 600mg Q6M20.38± 8.068
Day 121 fold rise
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M13.13± 8.439
Day 183 fold rise
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M7.28± 6.954
AZD7442: 1200 mg ONCE / 600mg Q6M6.90± 7.185
Day 212 fold rise
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M10.28± 6.969
AZD7442: 1200 mg ONCE / 600mg Q6M14.44± 7.457
Day 274 fold rise
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M7.06± 6.133
AZD7442: 1200 mg ONCE / 600mg Q6M8.99± 8.271
Day 365 fold rise
GroupValue95% CI
AZD7442: 600mg ONCE / 300mg Q3M12.64± 1.251
AZD7442: 1200 mg ONCE / 600mg Q6M2.84± 8.353

Adverse events — posted to ClinicalTrials.gov

Time frame: Safety data were recorded from the time of the first IMP administration throughout the study for an average safety follow up time of 48.85 weeks. This was shorter than the planned one of 105 weeks due to FDA's request to halt dosing.. Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

AZD7442: 600mg ONCE / 300mg Q3M
Serious: 13/124 (10%)
Deaths: 0/124
AZD7442: 1200 mg ONCE / 600mg Q6M
Serious: 10/124 (8%)
Deaths: 1/124

Serious adverse events (34 terms)

ReactionSystemAZD7442: 600mg ONCE / 300m…AZD7442: 1200 mg ONCE / 60…
PneumoniaInfections and infestations
Pneumonia bacterialInfections and infestations
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Abscess limbInfections and infestations
Covid-19Infections and infestations
DiverticulitisInfections and infestations
Escherichia pyelonephritisInfections and infestations
Escherichia sepsisInfections and infestations
Escherichia urinary tract infectionInfections and infestations
Gastroenteritis norovirusInfections and infestations
Acute myocardial infarctionCardiac disorders
Pulmonary sepsisInfections and infestations
SepsisInfections and infestations
Urinary tract infectionInfections and infestations
Urinary tract infection bacterialInfections and infestations
Angina pectorisCardiac disorders
Gastrointestinal anastomotic stenosisInjury, poisoning and procedural complications
Subdural haematomaInjury, poisoning and procedural complications
Angina unstableCardiac disorders
HypokalaemiaMetabolism and nutrition disorders
Anal squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to spineNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndromeNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Pituitary tumour benignNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (59 terms — click to expand)

ReactionSystemAZD7442: 600mg ONCE / 300m…AZD7442: 1200 mg ONCE / 60…
Covid-19Infections and infestations
NasopharyngitisInfections and infestations
HeadacheNervous system disorders
Urinary tract infectionInfections and infestations
DizzinessNervous system disorders
FatigueGeneral disorders
Viral upper respiratory tract infectionInfections and infestations
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
BronchitisInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
MyalgiaMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
Injection site pruritusGeneral disorders
AnaemiaBlood and lymphatic system disorders
Herpes zosterInfections and infestations
Respiratory tract infection viralInfections and infestations
FallInjury, poisoning and procedural complications
Blood thrombin increasedInvestigations
Diabetes mellitusMetabolism and nutrition disorders
Rheumatoid arthritisMusculoskeletal and connective tissue disorders
Acute kidney injuryRenal and urinary disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Respiratory tract congestionRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
ChillsGeneral disorders
Injection site painGeneral disorders
PainGeneral disorders
PyrexiaGeneral disorders
Seasonal allergyImmune system disorders
CystitisInfections and infestations
DiverticulitisInfections and infestations
PneumoniaInfections and infestations
Skin lacerationInjury, poisoning and procedural complications

Most-reported serious reactions: Pneumonia, Pneumonia bacterial, Acute respiratory failure, Anaemia, Abscess limb, Covid-19, Diverticulitis, Escherichia pyelonephritis.

Data from ClinicalTrials.gov NCT05375760 adverse events section.

Sponsor's own description

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

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. A Critical Analysis of the Use of Cilgavimab plus Tixagevimab Monoclonal Antibody Cocktail (Evusheld™) for COVID-19 Prophylaxis and Treatment.
    Focosi D, Casadevall A. · · 2022 · cited 52× · PMID 36146805 · DOI 10.3390/v14091999
  2. Tixagevimab/Cilgavimab in SARS-CoV-2 Prophylaxis and Therapy: A Comprehensive Review of Clinical Experience.
    Akinosoglou K, Rigopoulos EA, Kaiafa G, Daios S, et al · · 2022 · cited 23× · PMID 36680160 · DOI 10.3390/v15010118
  3. Accelerating therapeutics development during a pandemic: population pharmacokinetics of the long-acting antibody combination AZD7442 (tixagevimab/cilgavimab) in the prophylaxis and treatment of COVID-19.
    Clegg LE, Stepanov O, Schmidt H, Tang W, et al · · 2024 · cited 14× · PMID 38534112 · DOI 10.1128/aac.01587-23
  4. Impact of Sars-CoV-2 Prophylaxis with Tixagevimab-Cilgavimab in High-Risk Patients with B-Cell Malignancies: A Single-Center Retrospective Study.
    Assanto GM, Totaro M, Poggiali R, Delli Paoli A, et al · · 2023 · cited 1× · PMID 38028390 · DOI 10.4084/mjhid.2023.061
  5. P-1969. Safety, Immunogenicity, and Pharmacokinetics of Repeat Dosing with AZD7442 (Tixagevimab/Cilgavimab): Final Analysis of the ENDURE Phase 2, Dose-Ranging Study in Immunocompromised Participants
    · 2025

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