Versions Compared

Key

  • This line was added.
  • This line was removed.
  • Formatting was changed.
RequestNotes

Status

From the Rare Disease TAUG

From Stefan Konermann.

Rare Diseases Therapeutic Area User Guide, section 9.1, In Vivo Gene Therapy (Spinal Muscular Atrophy).

Email from Stephen on 2023-09-01.


Status
colourGreen
titleResolved
  From the Rare Disease TAUG

  • Added to the SDTMIG v4.0.

Status
colourYellow
titlein progress
From Stefan Konermann.


This example shows a Sars-CoV-2 vaccine study where the mechanism of delivery for the study vaccine antigenic component is based off of, and enabled by the viral vector technology. In this specific use-case, the transgene encoding the full-length, membrane-bound severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is incorporated into a recombinant, replication-incompetent Human Adenovirus Type 26 (Ad26) Vector . The Sars-CoV-2 spike protein expressed by the transgene is the antigenic component of this vaccine. The "Ad26.COV2.S" study vaccine is then administered to patients. Neutralizing anti-vector antibodies (i.e. anti-Ad26 vector antibody) are closely monitored at baseline and post-study vaccine exposure visits. This is because the occurrence of the anti-vector antibodies could significantly hinder the Ad26 vector's ability to deliver the Sars-CoV-2 spike protein transgene to target cells, and consequently, either inhibits the planned vaccine therapy, or diminishes the efficacy of the study vaccine after administration.

...

The example below shows a use-case of undesired, unwanted cellular immune responses toward a protein therapeutic delivered through the viral vector technology. In this case, T-cell responses to both the viral vector and the therapeutic peptide (which is translated from the transgene delivered by the viral vector), are measured before and after study treatment. The T cell responses to both the vector and the theraptucis peptide are considered as "undesired/unwanted", which are indicated by the ISCAT = VECTOR-INDUCED IMMUNOGENICITY, and ISCAT = ANTIDRUG T CELL-MEDIATED IMMUNOGENICITY.

Additionally, both anti-drug antibodies (ADA) and anti-drug T cell-mediated immunogenicity are considered as "anti-drug immunogenicity".

Dataset wrap
Nameis
Rowcaps

Rows 1-2:

Show the measurement of interferon gamma (ISMSCBCE) cytokine-secreting T cells (ISTEST) at baseline in response to stimulation by the viral vector and the therapeutic peptide (translated from the transgene delivered by the vector) in ISCNDAGT, respectively, prior to study treatment.

Rows 3-4:

Show the measurement of interferon gamma (ISMSCBCE) cytokine-secreting T cells (ISTEST) at visit 1 in response to stimulation by the viral vector and the therapeutic peptide (translated from the transgene delivered by the vector) in ISCNDAGT, respectively, after study treatment.

Dataset2

Row

STUDYID

DOMAIN

USUBJID

ISSEQ

ISREFID

ISTESTCD

ISTEST

ISMSCBCE

ISTSTCNDISCNDAGTISCATISSCAT

ISORRES

ISORRESU

ISSTRESC

ISSTRESN

ISSTRESU

ISSPEC

ISMETHOD

VISITNUMVISIT

ISDTC

1

RSV1230

IS

RSV1230-011

1

13998

CYKSCTCL

Cytokine-secreting T Cells

INTERFERON GAMMAWITH STIMULATING AGENTHUMAN ADENOVIRUS TYPE 26 VECTORVECTOR-INDUCED IMMUNOGENICITYCELLULAR IMMUNITY

5.1

SFC/10^6 PBMC

5.1

5.1

SFC/10^6 PBMC

PERIPHERAL BLOOD MONONUCLEAR CELL

ELISPOT

1BASELINE

2017-05-27

2

RSV1230

IS

RSV1230-011

2

13998

CYKSCTCL

Cytokine-secreting T Cells

INTERFERON GAMMAWITH STIMULATING AGENT

THERAPEUTIC PEPTIDE

ANTIDRUG T CELL-MEDIATED IMMUNOGENICITY

CELLULAR IMMUNITY

7.05

SFC/10^6 PBMC

7.05

7.05

SFC/10^6 PBMC

PERIPHERAL BLOOD MONONUCLEAR CELL

ELISPOT

1BASELINE

2017-05-27

3

RSV1230

IS

RSV1230-011

3

13998

CYKSCTCL

Cytokine-secreting T Cells

INTERFERON GAMMAWITH STIMULATING AGENTHUMAN ADENOVIRUS TYPE 26 VECTORVECTOR-INDUCED IMMUNOGENICITYCELLULAR IMMUNITY

157.8

SFC/10^6 PBMC

157.8

157.8

SFC/10^6 PBMC

PERIPHERAL BLOOD MONONUCLEAR CELL

ELISPOT

2VISIT 1

2017-08-27

4RSV1230ISRSV1230-011413998CYKSCTCLCytokine-secreting T CellsINTERFERON GAMMAWITH STIMULATING AGENTTHERAPEUTIC PEPTIDE

ANTIDRUG T CELL-MEDIATED IMMUNOGENICITY

CELLULAR IMMUNITY295.5

SFC/10^6 PBMC

295.5295.5

SFC/10^6 PBMC

PERIPHERAL BLOOD MONONUCLEAR CELL

ELISPOT2VISIT 12017-08-27