Household Contacts
Conditions
Keywords
seroconversion, viral shedding, DNA vector shedding
Brief summary
This study will include male and female participants who live or work in the same household as a patient in one of the fordadistrogene movaparvovec interventional studies. Up to 5 participants from the same household may be enrolled. The objective is to estimate the likelihood of NAb seroconversion to AAV9 in household contacts of a patient in one of the interventional studies who is treated with fordadistrogene movaparvovec gene therapy.
Detailed description
This single center study will include approximately 50 to 250 participants and is designed to estimate the likelihood of NAb seroconversion to AAV9 because of exposure to shed viral vector material released by a DMD patient treated with fordadistrogene movaparvovec in an interventional study. Eligible participants will undergo a blood draw provided by a Home Health Care Vendor at three home visits. The total duration of participation in this study is about 4 months, including up to 48 days for the screening/baseline period and about 56 days after the DMD patient of the same household is dosed with the investigational gene therapy in the interventional study. To maintain the blind in the blinded interventional studies, all C3391007 study participants and investigators as well as the sponsor will remain blinded to the Cohort assignment of the interventional study patient until the interventional study becomes unblinded.
Interventions
OTHERBlood Draw
Blood Samples for NAb and ADA to AAV9
Sponsors
Pfizer
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
0 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Males or females who weigh at least 9 kg. * Anticipated to be living or working in the same household as a patient in one of the fordadistrogene movaparvovec interventional studies for at least 4 months. * Anticipated to have \> 10 hours of contact per week and expected to have direct contact with the interventional study patient. * The interventional patient is dosed in the interventional study.
Exclusion criteria
* Prior treatment with gene therapy utilizing AAV vectors of any serotype.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants (Previously Seronegative for Neutralizing Antibodies [NAbs] to AAV9) Who Developed NAb to AAV9 at Day 28 After the Interventional Study Patient Was Dosed | Day 28 after the interventional study participant was dosed | Development of NAb to AAV9 was defined by an increase of \>=6-fold above Baseline titer in participants with a detectable, but negative test (ie, titer \>=1 and \<4) for NAb to AAV9 at Baseline. If there was an undetectable titer at Baseline (ie, titer \<1), then development of NAb to AAV9 was defined by a NAb to AAV9 titer \>=6. |
| Number of Participants (Previously Seronegative for NAb to AAV9) Who Developed NAb to AAV9 at Day 56 After the Interventional Study Patient Was Dosed | Day 56 after the interventional study participant was dosed | Development of NAb to AAV9 was defined by an increase of \>=6-fold above Baseline titer in participants with a detectable, but negative test (ie, titer \>=1 and \<4) for NAb to AAV9 at Baseline. If there was an undetectable titer at Baseline (ie, titer \<1), then development of NAb to AAV9 was defined by a NAb to AAV9 titer \>=6. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants (Previously Seronegative for Anti-Drug Antibody [ADA] to AAV9) Who Developed ADA to AAV9 at Day 28 After the Interventional Study Patient Was Dosed | Day 28 after the interventional study participant was dosed | Development of ADA to AAV9 was defined by a titer ≥300 in participants with a negative test (ie, titer \<50) for ADA to AAV9 at Baseline. |
| Number of Participants (Previously Seronegative for Anti-Drug Antibody [ADA] to AAV9) Who Developed ADA to AAV9 at Day 56 After the Interventional Study Patient Was Dosed | Day 56 after the interventional study participant was dosed | Development of ADA to AAV9 was defined by a titer ≥300 in participants with a negative test (ie, titer \<50) for ADA to AAV9 at Baseline. |
Countries
United States
Participant flow
Pre-assignment details
This was a low-interventional study to assess development of neutralizing Antibodies (NAbs) to adeno associated virus serotype 9 (AAV9) in household contacts of Duchenne Muscular Dystrophy (DMD) Patients Treated with fordadistrogene movaparvovec.
Participants by arm
| Arm | Count |
|---|---|
| Participants With Potential Fordadistrogene Movaparvovec Exposure People working or living in the same household of patients who were enrolled in an interventional study of fordadistrogene movaparvovec (including study C3391003 \[NCT04281485\] and C3391002 \[not listed on ClinicalTrials.gov\]) were enrolled. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Participants With Potential Fordadistrogene Movaparvovec Exposure |
|---|---|
| Age, Continuous | 41.0 Years STANDARD_DEVIATION 9.35 |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 7 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Number of Participants (Previously Seronegative for NAb to AAV9) Who Developed NAb to AAV9 at Day 56 After the Interventional Study Patient Was Dosed
Development of NAb to AAV9 was defined by an increase of \>=6-fold above Baseline titer in participants with a detectable, but negative test (ie, titer \>=1 and \<4) for NAb to AAV9 at Baseline. If there was an undetectable titer at Baseline (ie, titer \<1), then development of NAb to AAV9 was defined by a NAb to AAV9 titer \>=6.
Time frame: Day 56 after the interventional study participant was dosed
Population: Number of participants analyzed signifies number of participants evaluable for the outcome measure: Participants with a NAb titer undetectable (ie, titer \<1) or detectable, but negative test (ie, titer \>=1 and \<4) at Baseline were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Potential Fordadistrogene Movaparvovec Exposure | Number of Participants (Previously Seronegative for NAb to AAV9) Who Developed NAb to AAV9 at Day 56 After the Interventional Study Patient Was Dosed | 0 Participants |
Primary
Number of Participants (Previously Seronegative for Neutralizing Antibodies [NAbs] to AAV9) Who Developed NAb to AAV9 at Day 28 After the Interventional Study Patient Was Dosed
Development of NAb to AAV9 was defined by an increase of \>=6-fold above Baseline titer in participants with a detectable, but negative test (ie, titer \>=1 and \<4) for NAb to AAV9 at Baseline. If there was an undetectable titer at Baseline (ie, titer \<1), then development of NAb to AAV9 was defined by a NAb to AAV9 titer \>=6.
Time frame: Day 28 after the interventional study participant was dosed
Population: Number of participants analyzed signifies number of participants evaluable for the outcome measure: Participants with a NAb titer undetectable (ie, titer \<1) or detectable, but negative test (ie, titer \>=1 and \<4) at Baseline were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Potential Fordadistrogene Movaparvovec Exposure | Number of Participants (Previously Seronegative for Neutralizing Antibodies [NAbs] to AAV9) Who Developed NAb to AAV9 at Day 28 After the Interventional Study Patient Was Dosed | 0 Participants |
Secondary
Number of Participants (Previously Seronegative for Anti-Drug Antibody [ADA] to AAV9) Who Developed ADA to AAV9 at Day 28 After the Interventional Study Patient Was Dosed
Development of ADA to AAV9 was defined by a titer ≥300 in participants with a negative test (ie, titer \<50) for ADA to AAV9 at Baseline.
Time frame: Day 28 after the interventional study participant was dosed
Population: Number of participants analyzed signifies number of participants evaluable for the outcome measure: Participants with an ADA titer negative at Baseline were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Potential Fordadistrogene Movaparvovec Exposure | Number of Participants (Previously Seronegative for Anti-Drug Antibody [ADA] to AAV9) Who Developed ADA to AAV9 at Day 28 After the Interventional Study Patient Was Dosed | 0 Participants |
Secondary
Number of Participants (Previously Seronegative for Anti-Drug Antibody [ADA] to AAV9) Who Developed ADA to AAV9 at Day 56 After the Interventional Study Patient Was Dosed
Development of ADA to AAV9 was defined by a titer ≥300 in participants with a negative test (ie, titer \<50) for ADA to AAV9 at Baseline.
Time frame: Day 56 after the interventional study participant was dosed
Population: Number of participants analyzed signifies number of participants evaluable for the outcome measure: Participants with an ADA titer negative at Baseline were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Potential Fordadistrogene Movaparvovec Exposure | Number of Participants (Previously Seronegative for Anti-Drug Antibody [ADA] to AAV9) Who Developed ADA to AAV9 at Day 56 After the Interventional Study Patient Was Dosed | 0 Participants |