Infections

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Neoplasms

Blood and Lymph Conditions

Symptoms and General Pathology

COVID-19

Hematologic Neoplasms

Pneumonia

Pneumonia, Viral

Communicable Diseases

Respiratory Tract Infections

Virus Diseases

Coronavirus Infections

Coronaviridae Infections

Nidovirales Infections

RNA Virus Infections

Lung Diseases

Respiratory Tract Diseases

Hematologic Diseases

Francesco Passamonti, MD

Covid-19 is associated with a mortality rate of 33-37% in patients with hematological malignancies.

At present, the anti-SARS-CoV-2 vaccination represents the most effective strategy for the prevention of Covid-19. Patients with malignancies were excluded from the trials leading to the approval of Comirnaty, Moderna, Vaxzevria and Janssen vaccines. The immunogenicity of these vaccines in immunocompromised patients or with hematological malignancies is an unmet clinical need.

The aim of the study is to evaluate the efficacy of vaccination in adult patients with hematological malignancies, who received vaccination according to Italian rules and were in treatment at the Hematology Unit of Varese, Italy Efficacy will be evaluated in terms of serological response, cellular-mediated immune response and prevention of Covid-19.

The duration of the study will be 24 months.

Covid-19 is associated with a mortality rate of 33-37% in patients with hematological malignancies (Passamonti et al, 2020; Garcia-Suarez et al, 2020). Currently, there is little information on the serological response following SARS-Cov-2 infection in this specific population.

At present, the anti-SARS-CoV-2 vaccination represents the most effective strategy for the prevention of Covid-19. The anti-SARS-CoV-2 vaccines currently approved by the European Medicines Agency (EMA) and the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA) are: the BNT162b2 SARS-Cov-2 (Pfizer-BioNTech, Comirnaty) vaccine, the mRNA-1273 SARS-Cov-2 (Moderna) vaccine, the ChAdOx1 nCoV-19 (Vaxzevria) vaccine, and the Ad26.COV2.S (Janssen) vaccine.

The double-dose regimen of Pfizer-BioNTech vaccine showed 95% efficacy at preventing Covid-19 (Polack et al, 2020), the double-dose regimen of Moderna vaccine showed 94.1% efficacy (Baden et al, 2021), the double-dose regimen of Vaxzevria vaccine showed 70.4% efficacy (Voysey et al, 2021), while the single-dose regimen of Janssen vaccine was found to be 66.1% effective (Sadoff et al, 2021).

The Italian national Covid-19 vaccination plan included patients with active malignancies in the second priority group, recognizing the importance of protecting this vulnerable population from SARS-Cov-2 infection. Since vaccine clinical trials excluded patients with malignancies and patients undergoing immunosuppressive therapies, the immunological response to anti-SARS-CoV-2 vaccines in these patients is currently unknown.

In this prospective, cohort, non-interventional study, our objective is to evaluate both the humoral and the cellular immune response to anti-SARS-CoV-2 vaccination in adults with hematological malignancies. For each patient the immune response will be evaluated after a minimum of 28 days from the completion of the vaccination regimen. Then, it will be reassessed after 6 and 12 months. In our center, the humoral immune response will be assessed by using the DiaSorin's LIAISON SARS-CoV-2 S1/S2 IgG test, which quantifies the level of anti-SARS-CoV-2 IgG antibodies that are active against the S1 and S2 subunits of the S protein. The cell-mediated immune response will be assessed on peripheral blood cells through a phenotypic and functional analysis by flow cytometry and through the ELISPOT test. Each patients will sign an informed consensus for the participation. The total duration of the study will be 24 months.

Immunogenicity of Covid-19 Vaccination for Patients With Hematological Malignancies

Prospective, Cohort, Non-interventional, Single-center Clinical Study of Immune Response Status to SARS-CoV-2 / Covid-19 Vaccination in Patients With Haematological Malignancies.

The percentage of patients with positive antibody titer (≥ 12 AU / mL) after at least 28 days from vaccination.

The percentage of patients with positive antibody titer (≥ 12 AU / mL) after at least 28 days from vaccination in myeloid, lymphoid and plasma cell dyscrasias sub-categorized by status of disease, status and type of treatment.

The percentage of patients with positive antibody titer (≥ 12 AU / mL) after at least 28 days from vaccination described by vaccine brand (currently Comirnaty, Moderna, Vaxzevria, Janssen).

The distribution and median of the antibody titer at least 28 days after vaccination.

The difference between the antibody titer at 28 days and at 6 and 12 months after vaccination.

The percentage of patients who generated immune cells with IFN-gamma cytokine response after at least 28 days, 6 and 12 months after vaccination.

The percentage of patients with any among: 1) positive molecular swab by RT-PCR, 2) documented symptomatic Covid-19 disease; 3) hospitalization for Covid-19; 4) documented severe Covid-19 disease; 5) death from Covid-19 despite vaccination.

Ospedale di Circolo - Fondazione Macchi

Principal Investigator

Skin and Connective Tissue Diseases

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Vaccines

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants will receive up to 9 doses of mRNA-4157 (every 21 days). Participants may continue on pembrolizumab (every 21 days) until disease recurrence, unacceptable toxicity, or they undergo up to 18 total cycles (approximately 1 year of treatment), whichever is sooner.

Participants will receive pembrolizumab (every 21 days) until disease recurrence, unacceptable toxicity, or they undergo up to 18 total cycles (approximately 1 year of treatment), whichever is sooner.

mRNA-4157

Moderna Clinical Trials Support Center

Montaser Shaheen

Kevin Kim, MD

Mark Faries, MD

Karl Lewis, MD

Sarah Weiss, MD

Geoffrey Gibney, MD

Sajeve Thomas

Jason Luke

Ryan Sullivan, MD

Elizabeth Buckbinder

Leonel Hernandez Aya, MD

Andrew Pecora, MD

Jeffrey Weber, MD

Mathew Taylor

Meredith McKean, MD

Charles Cowey, MD

Tarek Meniawy

The purpose of this study is to assess whether postoperative adjuvant therapy with mRNA-4157 and pembrolizumab improves recurrence free survival (RFS) compared to pembrolizumab alone in participants with complete resection of cutaneous melanoma and a high risk of recurrence.

An Efficacy Study of Adjuvant Treatment With the Personalized Cancer Vaccine mRNA-4157 and Pembrolizumab in Participants With High-Risk Melanoma (KEYNOTE-942)

A Phase 2 Randomized Study of Adjuvant Immunotherapy With the Personalized Cancer Vaccine mRNA-4157 and Pembrolizumab Versus Pembrolizumab Alone After Complete Resection of High-Risk Melanoma (KEYNOTE- 942)

RFS is defined as the time between the date of first dose of pembrolizumab and the date of recurrence (local, regional, or distant metastasis), new primary melanoma, or death (whatever the cause), whichever occurs first.

DMFS is defined as the time between the date of first dose of pembrolizumab and the date of the first distant metastasis or the date of death (whatever the cause), whichever occurs first.

Merck Sharp & Dohme LLC

ModernaTX, Inc.

Participants will receive mRNA-4157 via an intramuscular (IM) injection on Day 1 of each 21-day cycle for up to 9 cycles.

Participants will receive mRNA-4157 via an IM injection on Day 1 of each 21-day cycle for up to 9 cycles and pembrolizumab via IV infusion on Day 1 of each 21-day cycle until progression, unacceptable toxicity, or up to 35 cycles (approximately 2 years of treatment), whichever is sooner.

Participants will receive mRNA-4157 via an IM injection on Day 1 of each 21-day cycle and a SoC treatment every 2 weeks (Q2W) on Day 1 of each 21-day cycle starting from Cycle 5 of mRNA-4157 for up to 12 cycles.

Participants will receive mRNA-4157 via IM injection on Day 1 of each 21-day cycle for up to 9 cycles and pembrolizumab via IV infusion on Day 1 of each 21-day cycle until progression, unacceptable toxicity, or up to 35 cycles (approximately 2 years of treatment), whichever is sooner.

Participants will receive mRNA-4157 via IM injection on Day 1 of each 21-day cycle for up to 9 cycles and pembrolizumab via IV infusion on Day 1 of each 21-day cycle until progression, unacceptable toxicity, or up to 18 cycles (approximately 1 year of treatment), whichever is sooner.

Participants will receive mRNA-4157 via IM injection on Day 1 of each 21-day cycle, pembrolizumab every 6 weeks (Q6W) via IV infusion, and SoC chemotherapy every 3 weeks (Q3W) for up to 4 cycles during the perioperative and adjuvant phases.

Participants will receive mRNA-4157 via IM injection on Day 1 of each 21-day cycle, pembrolizumab Q6W via IV infusion, and SoC chemotherapy Q3W for up to 4 cycles during the perioperative and adjuvant phases.

Participants will receive mRNA-4157 via IM injection on Day 1 of each 21-day cycle, pembrolizumab Q3W via IV infusion, and SoC chemotherapy Q2W or Q3W for up to 4 cycles during the perioperative and adjuvant phases.

SoC Treatment

The purpose of this study is to assess the safety, tolerability, and immunogenicity of mRNA-4157 alone and in combination in participants with solid tumors.

This is a multi-part, dose-escalation study of mRNA-4157 monotherapy in participants with resected solid tumors (Part A), mRNA-4157 monotherapy lead-in and then in combination with standard of care (SoC) adjuvant chemotherapy followed by mRNA-4157 monotherapy in participants with resected pancreatic ductal adenocarcinoma (PDAC) (Part A2), mRNA-4157 in combination with pembrolizumab in participants with both unresectable (locally advanced or metastatic) solid tumors (Parts B and C) and adjuvant resected cutaneous melanoma (Part D), and mRNA-4157 in combination with pembrolizumab and SoC chemotherapy in peri-operative setting in participants with non-squamous non-small cell lung cancer (NSCLC) (Part E1), squamous cell NSCLC (Part E2), and gastric/ gastroesophageal (GEJ) cancer (Part E3). Parts A and B will include a dose escalation phase of the study to identify doses of mRNA-4157 for the expansion phase of the study. Doses of mRNA-4157 will be administered to participants in a dose escalation regimen. Participants in Parts A2, B, C, D, E1, E2 and E3 dose expansion phase will receive mRNA-4157 at a recommended dose for expansion.

Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone and in Combination in Participants With Solid Tumors

A Phase 1, Open-Label, Multicenter Study to Assess the Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone and in Combination in Participants With Solid Tumors

ORR is defined as the proportion of participants whose best overall response is complete response (CR) or partial response (PR).

DoR is defined as time from first tumor response (partial or complete) until either radiological disease progression, clinical/symptomatic disease progression or death (whichever is sooner).

PFS is defined as time between the date of first dose of pembrolizumab and the date of either radiological disease progression, clinical/symptomatic disease progression or death (whichever is sooner).

OS is defined as time between the date of the first dose of study drug and the date of death due to any cause.

RFS is defined as the time between the date of first dose of mRNA-4157 and the date of one of the following events: radiological disease relapse, clinical/symptomatic disease progression as assessed by the investigator or death due to any cause.

Presence or absence of ctDNA prior to start of treatment as well as across longitudinal study timepoints, and association with RFS.

EFS is defined as the time from date of the first dose of study drug to the first of the following events: radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local, regional, or distant recurrence, or death due to any cause and will be determined either by biopsy assessed by local pathologist or by investigator-assessed imaging using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

EFS, based on RECIST 1.1, is defined as the time from date of the first dose of study drug to the first of the following events: radiographic disease progression per RECIST 1.1; local, regional or distant recurrence as assessed by computed tomography scan or biopsy if indicated (for participants who are disease free after surgery); clinical progression as evidenced by peritoneal carcinomatosis confirmed by preoperative laparoscopy or laparotomy (for participants who are confirmed to be free of peritoneal involvement by laparoscopy at screening); or death due to any cause.

Heart and Blood Diseases

Immune System Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Lymphoma

Leukemia

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Lymphosarcoma

100 mcg (0.5 mL) mRNA-1273 injection (IM) on days 1 and 29; with option for subsequent booster dose(s), 100 mcg (0.5 mL) mRNA-1273 injection (IM) no less than 4 weeks after day 29

100 micrograms (0.5 mL) mRNA-1273 injection on D1

A rapid response, proprietary messenger RNA (mRNA)-based vaccine platform. 100 mcg administered IM on Day 1 and 29 for vaccine naive cohorts or on Day 1 for vaccine booster cohorts. Participants may receive up to 3 booster injections on study

mRNA-1273

Elad Sharon, M.D.

Background:

COVID-19 is a viral infection. It has spread rapidly across the globe. It has overwhelmed health systems. Researchers are concerned that it may undo years of progress in the reduction of cancer-specific death. They want to test a vaccine that might protect people with cancer from COVID-19.

Objective:

To test the safety and efficacy of a vaccine using mRNA-1273 that may protect people with cancer from COVID-19.

Eligibility:

Adults ages 18 and older who have a solid tumor or blood cancer and who may benefit from a

vaccine that might prepare their immune system for fighting and preventing infection from COVID-19. Patients with solid tumors must be receiving treatment with an immunotherapy agent

Design:

Participants will be screened with a medical history, medicine review, and physical exam. They will have blood tests. They will have a pregnancy test if needed.

Participants will get 2 doses of the mRNA-1273 vaccine if they have not been vaccinated already. It will be injected into a muscle in the arm on Days 1 and 29. They will be followed for 12 months after the second dose.

Participants will have study visits at the Clinical Center on Days 1, 29, 36,57, 209, and 394. Some visits will last about 4-6 hours. Patients will be able to get up to 3 doses of mRNA-1273 as a booster on trial if they have already completed a primary series of a vaccine. Participants who have already received a booster dose of vaccine will be able to enroll to receive additional boosters. It will be injected into a muscle in the arm on Day 1. Participants will be followed for 12 months after their last booster injection. Participants who receive booster doses will have study visits at the Clinical Center on Days 1, 29, 57, 180 and 360.

Participants will give blood and saliva samples for research.

Participation will last about 16 months.

Design of the Study:

This is an open-label, multicenter clinical trial designed to evaluate the safety, reactogenicity and primary immunogenicity of the mRNA-1273 vaccine administered in 2 doses, 28 days apart, in participants who have hematological malignancy and are immunosuppressed due to their disease and/or treatment or receiving a PD-1/PDL-1 inhibitor for treatment of a solid tumor can be associated with appropriately high rates of development of neutralizing antibodies of mRNA-1273. The trial will also evaluate the safety, reactogenicity and immunogenicity after administration of additional booster doses of the vaccine.

Study Phase:\<TAB\>2

Study Population:\<TAB\>

For the vaccine-na(SqrRoot) ve cohorts, up to 80 participants will be enrolled.

* 20 participants with solid tumor malignancies who have initiated PD1/PDL1 inhibitor therapy as part of standard of care and are deemed to have a stable regimen without the need for any immunosuppressive therapy or corticosteroids.
* 60 participants with leukemia, lymphoma, multiple myeloma and participants post-allogeneic stem cell transplant will be enrolled based on their perceived risk of immunosuppression.

For the previously-vaccinated (also known as "booster") cohorts, up to 140 participants will be enrolled for booster injections. All participants on the vaccine-na(SqrRoot) ve cohorts will have the option of receiving boosters; however, they will not count towards the maximum accrual goal for each of the booster groups. Note: All participants will be eligible to receive up to three (3) booster doses of vaccine on study.

* 20 participants with solid tumor malignancies who have initiated PD1/PDL1 inhibitor therapy as part of standard of care and are deemed to have a stable regimen without the need for any immunosuppressive therapy or corticosteroids.
* 20 participants with chronic lymphocytic leukemia who are not currently on any therapies
* 20 participants with chronic lymphocytic leukemia who are on BTK inhibitor therapy alone
* 30 participants with any CAR T Cell therapy for a hematologic malignancy
* 20 participants post-allogeneic stem cell transplant
* 20 participants with other hematologic malignancies
* Up to 10 participants with any solid tumor who are not otherwise eligible for any of the other cohorts

Number of Sites: 2

Description of Study Product or Intervention:

mRNA-1273 Injection (Drug Product) is an LNP dispersion containing a single mRNA sequence (Drug Substance) that encodes the SARS-CoV-2 S glycoprotein stabilized in the prefusion conformation. The mRNA-1273 Drug Substance is combined with a mixture of 4 lipids common to the Moderna s mRNA vaccine platform: SM-102 (a custom-manufactured, ionizable lipid) and 3 commercially available lipids, cholesterol, DSPC, and PEG2000-DMG (https://doi.org/10.1038/s41587-020- 00807-1). mRNA-1273 Injection is provided as a sterile solution for injection, white to off white dispersion in appearance.

Presentation: mRNA-1273 Injection is provided as a sterile solution for injection at a concentration of 0.2 mg/mL in 20 mM trometamol (Tris) buffer containing 87 mg/mL sucrose and 4.3 mM acetate, at pH 7.5. mRNA-1273 Injection is presented in 10R USP Type I borosilicate glass vials with PLASCAP vial seal containing a 20 mm FluroTec-coated plug stopper and has a 6.3 mL nominal fill volume. This vial may be used for more than one participant.

mRNA-1273 Injection must be stored frozen at -15 degrees C to -25 degrees C until thawed for use and then stored refrigerated at 2 degrees C to 8 degrees C for up to 30 days (once thawed it must not be refrozen)

Each dose of 100 mcg (0.5 mL) will be administered via IM injection into the deltoid muscle on Days 1 and 29 (+/- 3 days) for the vaccine-na(SqrRoot) ve cohorts. Up to 3 additional ( booster ) doses of the vaccine may also be administered.

Study Objectives:

Primary:

* To evaluate the safety and reactogenicity of the mRNA- 1273 vaccine administered in 2 doses, 28 days apart, in participants who have a hematological malignancy and are immunosuppressed due to their disease and/or treatment, or receiving a PD-1/PDL-1 inhibitor for treatment of a solid tumor for patients who are vaccine-na(SqrRoot) ve
* To evaluate the safety and reactogenicity of booster doses of mRNA-1273 vaccine administered to participants who have previously received an mRNA or alternative vaccine regimen
* To evaluate the safety and reactogenicity of booster doses of mRNA-1273 administered to participants with CLL who are either off treatment or are engaging in a 3-week BTK inhibitor interruption to enhance vaccine immunogenicity
* To assess the immunogenicity of mRNA-1273 in participants with cancer, as assessed by the titer or level of specific binding antibody (bAb)

Secondary:

* To evaluate the immunogenicity of the mRNA-1273 vaccine administered in 2 doses 28 days apart, as assessed by the titer or level of neutralizing antibody (nAb) in the vaccine-na(SqrRoot) ve cohorts
* To evaluate the immunogenicity of booster doses of mRNA-1273 vaccine administered to participants who have previously been vaccinated against SARS-CoV2 with any prior vaccine regimen. as assessed by the titer or level of neutralizing antibody (nAb)

Exploratory:

* To assess immune responses against the SARS-CoV-2 nucleocapsid and spike proteins
* To evaluate salivary measurement of IgG antibodies against the SARS-CoV-2 nucleocapsid and spike (S) proteins

Duration of Individual Participant Participation:

The duration for each individual participation is approximately 14 months (from first contact to last visit).

Study Duration:

Study duration is anticipated to be 16 months (from start of screening to last Participant/last visit).

A Trial of the Safety and Immunogenicity of the COVID-19 Vaccine (mRNA-1273) in Participants With Hematologic Malignancies and Various Regimens of Immunosuppression, and in Participants With Solid Tumors on PD1/PDL1 Inhibitor Therapy, Including Boost...

A Trial of the Safety and Immunogenicity of the COVID-19 Vaccine (mRNA-1273) in Participants With Hematologic Malignancies and Various Regimens of Immunosuppression, and in Participants With Solid Tumors on PD1/PDL1 Inhibitor Therapy, Including Booster Doses of Vaccine

.All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

-Solicited local and systemic Adverse Reactions (ARs) through 7 days after each injection. -Unsolicited AEs through 28 days after each injection. -SAEs throughout the entire study period. - Vital sign measurements and physical examination findings.

-Solicited local and systemic Adverse Reactions (ARs) through 7 days after injection. -Unsolicited AEs through 28 days after injection. - SAEs throughout the entire study period. - Vital sign measurements and physical examination findings

- Titer or level of specific binding antibody (bAb), in participants who have a hematological malignancy and are immunosuppressed due to their disease and/or treatment or receiving a PD-1/PDL-1 inhibitor for treatment of a solid tumor - Titer or level of SARS-CoV-2-specific binding antibody (bAb) measured by ELISA on Day 1, Day 29, Day 36, Day 57, Day 209, and Day 394.

For Vaccine Naive Arm: Day 1, Day 29, Day 36, Day 57, Day 209, and Day 394 and for Booster Arm: Day 1, Day 29, Day 57, Day 180, and Day 360: -Titer or Level of SARS-CoV-2-specific neutralizing antibody (nAb) -Seroconversion due to vaccination as measured by an increase of SARS-CoV-2-specific nAb titer or level defined as -For subjects with no detectable antibody titer (\< LOD) at baseline: post-vaccination titer = LLOQ -For subjects with a positive baseline titer (\> LOD): post-vaccination titer = 4 times the LLOQ -For subjects with a baseline titer = LLOQ: post-vaccination titer = a 4-fold rise compared with baseline titer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Immunogenicity of Covid-19 Vaccination for Patients With Hematological Malignancies	NCT04878822	Immunogenicity Hematological M... Covid-19 Vaccine Respons...		18 Years -	Ospedale di Circolo - Fondazione Macchi
An Efficacy Study of Adjuvant Treatment With the Personalized Cancer Vaccine mRNA-4157 and Pembrolizumab in Participants With High-Risk Melanoma (KEYNOTE-942)	NCT03897881	Melanoma	mRNA-4157 Pembrolizumab	18 Years -	ModernaTX, Inc.
Immunogenicity of Covid-19 Vaccination for Patients With Hematological Malignancies	NCT04878822	Immunogenicity Hematological M... Covid-19 Vaccine Respons...		18 Years -	Ospedale di Circolo - Fondazione Macchi
Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone and in Combination in Participants With Solid Tumors	NCT03313778	Solid Tumors	mRNA-4157 Pembrolizumab SoC Treatment	18 Years -	ModernaTX, Inc.
A Trial of the Safety and Immunogenicity of the COVID-19 Vaccine (mRNA-1273) in Participants With Hematologic Malignancies and Various Regimens of Immunosuppression, and in Participants With Solid Tumors on PD1/PDL1 Inhibitor Therapy, Including Boost...	NCT04847050	Solid Tumor Mal... Hematologic Mal... Leukemia Lymphoma Multiple Myelom...	mRNA-1273	18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for moderna

Every month we try and update this database with for moderna cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for moderna

Every month we try and update this database with for moderna cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for moderna cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.