SABRE: A Single-arm Prospective Study Measuring Safety and Tolerability of SARS-CoV-2 Neutralising Antibodies in High-risk Populations

NCT05393999 | Withdrawn Phase 2 DMC

• 2 other identifiers: 21HH67472021-003033-10
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The SABRE study is a single-arm prospective study measuring safety, tolerability and pharmacokinetics of two SARS-CoV-2 neutralising antibodies (BMS-986414 and BMS-986413) amongst high-risk special populations of vaccine non-responders. The aim is to test the hypothesis that for individuals who fail to mount a measurable immune response to a routinely offered SARS-CoV-2 prophylactic vaccine or for those who are not able to receive such a vaccine (for example those receiving a bone marrow transplant or starting chemotherapy treatment), the receipt of subcutaneous injection of two long-acting neutralising antibodies BMS-986414 and BMS-986413 will confer durable high titres and subsequent immunological protection against SARS-CoV-2 infection.120 eligible participants will be enrolled and followed up for 48 weeks after the one-time dosing visit. Primary inclusion criteria are patients age 18 years and older and either 1) have received two doses of a routine NHS standard of care SARS-Cov-2 vaccine and do not have detectable serum SARS-CoV-2 anti-spike antibodies in routine NHS assays more than two weeks post-vaccination, or do not have protective levels of antibody or 2) be ineligible to receive a SARS-CoV-2 prophylactic vaccine. This could be because they need to commence immediate systemic chemotherapy or receive bone marrow and therefore the requirement to initiate profound immune suppression. Primary objectives are to determine the safety, tolerability and detectable SARS-CoV-2 antibody by specific PPD assay in serum at 12 weeks after enrolment.

Conditions

SARS-CoV2 Infection; SARS-CoV-2 Acute Respiratory Disease; Myeloma; Leukemia; Lymphoma; Immune Thrombocytopenia; Thrombotic Thrombocytopenic Purpura (TTP)

Outcome Measures

Primary Outcomes (4)

• Experience at least one Adverse Event of Interest (AEI).

  Number and proportion of participants who experience at least one AEI. The total number of AEIs (where multiple events per individual are counted) will also be reported.

  Week 12

• Experience at least one Serious Adverse Event (SAE).

  Number and proportion of participants who experience at least one SAE. The total number of SAEs (where multiple events per individual are counted) will also be reported.

  Week 12

• Antibody level of BMS-986414 in plasma/serum, measured using the PK assay.

  This will be summarised using the mean, alongside an appropriate measure of variability, anticipated to be 95% confidence interval.

  Week 12

• Antibody level of BMS-986413 in plasma/serum, measured using the PK assay.

  This will be summarised using the mean, alongside an appropriate measure of variability, anticipated to be 95% confidence interval.

  Week 12

Secondary Outcomes (8)

• Proportion achieving antibody levels of BMS-986414 in plasma/serum [measured using the PK assay] above the target PK threshold (2 ug/mL).

  Weeks 1, 4, 8, 12, 24

• Proportion achieving antibody levels of BMS-986413 in plasma/serum [measured using the PK assay] above the target PK threshold (2 ug/mL).

  Weeks 1, 4, 8, 12, 24

• Antibody levels of BMS-986414 in plasma/serum measured using the PK assay.

  Weeks 1, 4, 8, 24

• Antibody levels of BMS-986413 in plasma/serum at measured using the PK assay.

  Weeks 1, 4, 8, 24

• Antibody levels of BMS-986414 in plasma/serum measured by NHS assay.

  Weeks 1, 4, 8 12, 18, 24, 32, 40, 48

Study Arms (1)

BMS-986414 and BMS-986413

EXPERIMENTAL

1. Broadly neutralising antibody:BMS-986414 This long-acting antibody will be prescribed to all participants and given as one subcutaneous injection of 200 mg. 2. Broadly neutralising antibody: BMS-986413 This long-acting antibody will be prescribed to all participants and given as one subcutaneous injection of 200 mg

Biological: BMS-986414; Biological: BMS-986413

Interventions

BMS-986414 BIOLOGICAL

Broadly neutralising antibodies BMS-986414

Also known as: C135-LS

BMS-986414 and BMS-986413

BMS-986413 BIOLOGICAL

Broadly neutralising antibodies BMS-986413

Also known as: C144-LS

BMS-986414 and BMS-986413

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥18 years old at screening;
• Able to give informed written consent including consent to long-term follow-up;
• Willing and able to comply with visit schedule and provide blood sampling;
• Have received at least two doses of a routine NHS standard of care SARS-Cov-2 vaccine and do not have detectable serum SARS-CoV-2 anti-spike antibodies in routine NHS assays \> two weeks post 2nd vaccination, including:
• Solid organ transplant recipients;
• People with specific haematological diseases;
• People undergoing active chemotherapy, having immunotherapy or other continuing antibody or targeted therapy that affect immune system;
• People with cancers of the blood or bone marrow such as leukaemia, lymphoma or myeloma who are at any stage of treatment;
• People who have had bone marrow or stem cell transplants in the last 6 months or who are still taking immunosuppression drugs;
• People who are receiving long-term immune suppression therapy for ny other condition
• Be ineligible to receive a SARS-CoV-2 prophylactic vaccine for any of the following reasons:
• The need to commence immediate systemic chemotherapy;
• The need to receive a bone-marrow and therefore the requirement to initiate profound immune suppression
• Have an estimated life expectancy of \> 12 weeks;
• Females capable of becoming pregnant\* must agree to use hormonal contraception, intrauterine device, intrauterine hormone-releasing system, or to complete abstinence\*\* from at least four weeks before the first antibody injection and for 20 months after the last antibody injection

You may not qualify if:

• Current SARS-CoV-2 infection confirmed by SARS-CoV-2 RT-PCR positive result from nasopharyngeal swab within the past 10 days and up to 24 hours prior to enrolment;
• Participation in any other clinical trial of an experimental agent or any non-interventional study where additional blood draws are required; participation in observational studies is permitted. Patients in survival follow up of another clinical trial of an investigational medicinal product (CTIMP) study may be considered if more than 5 half lives have passed since last CTIMP treatment and with permission of the medical monitor for the other study;
• History of anaphylaxis or severe adverse reaction to antibody injections, or hypersensitivity to neutralising antibodies or to any constituent products or excipients thereof;
• Treatment with intravenous immunoglobulin (IVIG) or other investigational treatments planned during the duration of the trial;
• Clinically significant abnormal blood test results at screening including:
• Moderate to severe hepatic impairment as defined by Child-Pugh classification;
• ALT \>5 x ULN;
• INR \>1.5
• Pregnancy or breastfeeding

Sponsors & Collaborators

• Imperial College Healthcare NHS Trust: lead
• Imperial College London: collaborator
• University of Oxford: collaborator
• Oxford University Hospitals NHS Trust: collaborator

Study Sites (1)

Imperial College Heathcare NHS Trust

London, United Kingdom

Location

MeSH Terms

Conditions

COVID-19; Neoplasms, Plasma Cell; Leukemia; Lymphoma; Purpura, Thrombocytopenic, Idiopathic; Purpura, Thrombotic Thrombocytopenic

Interventions

ogalvibart; crexavibart

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Thrombophilia

Study Officials

• Lucy Cook

  Imperial College NHS Trust London

  PRINCIPAL INVESTIGATOR

• Andy Peniket

  Oxford University Hospitals NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2021
• First Posted: May 27, 2022
• Study Start: November 29, 2021
• Primary Completion: March 4, 2022
• Study Completion: March 4, 2022
• Last Updated: April 24, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)