Safety, reactogenicity, and immunogenicity of a 2-dose Ebola vaccine regimen of Ad26.ZEBOV followed by MVA-BN-Filo in healthy adult pregnant women: study protocol for a phase 3 open-label randomized controlled trial

Karita, Etienne; Nyombayire, Julien; Ingabire, Rosine; Mazzei, Amelia; Sharkey, Tyronza; Mukamuyango, Jeannine; Allen, Susan; Tichacek, Amanda; Parker, Rachel; Priddy, Frances; Sayinzoga, Felix; Nsanzimana, Sabin; Robinson, Cynthia; Katwere, Michael; Anumendem, Dickson; Leyssen, Maarten; Schaefer, Malinda; Wall, Kristin M.

doi:10.1186/s13063-022-06360-3

Trials

Table 2 Schedule of activities—women in group A

From: Safety, reactogenicity, and immunogenicity of a 2-dose Ebola vaccine regimen of Ad26.ZEBOV followed by MVA-BN-Filo in healthy adult pregnant women: study protocol for a phase 3 open-label randomized controlled trial

Visit #	1	2	3	4	5	6	7 ^a	8	9	10	11^a	EE
Visit timing^p		Dose 1	Dose 1 + 7 days	Dose 1 + 28 days	Dose 2	Dose 2 + 7 days	Dose 2 + 21 days	Dose 2 + 28 days	Pregnancy completion/ termination	PP 1 + 42	Dose 1 + 365 days	Early Exit
Visit day and window	− 28 to 1	D1	D8 ± 3 days	D29 ± 7 days	D57 − 14 days, + 28 days	D64 ± 3 days	D78 ± 3 days	D85 ± 7 days	PP 1 ^b + 2 days	PP 43 ^c ± 14 days	Dose 1 + 365 ± 28 days
Visit type	Screening	DOSE 1 group A	Safety	Safety	DOSE 2 group A	Safety	Immuno	Safety	Safety and immuno	Safety	Safety and immuno	Early exit
Assessment of understanding	•
Written informed consent (ICF) ^d	•
Inclusion/exclusion criteria	•	•
Demographics ^e	•
Medical and obstetric history ^f; pre-pregnancy and pre-study meds	•
Physical examination ^f	•				•					•		•
Obstetric exam ^f	•	•			•				•			•^o
Targeted physical exam ^f		•	•	•		•	•	•			•
Vital signs ^f incl. body temperature	•		•	•		•	•	•	•	•	•	•
Urine pregnancy test ^g	•
Hematology, chemistry ^g	•
Urine dipstick/urinalysis ^g	•	•		•	•			•
Syphilis, HIV, hepatitis B and C, malaria screening^g	•
Obstetric ultrasound ^h	•	•^h						•				•^o
Biometric scan	•	•	•	•	•	•	•	•	•	•	•	•
Contact information	•	•	•	•	•	•	•	•	•	•	•	•
Randomization		•
Pre-vaccination symptoms ⁱ
Vaccination		•			•
30 min post-vaccination observation ^j		•			•
Solicited AE collection ^k		•	•		•	•
Unsolicited AE collection ^k		•	•	•	•	•	•	•
Distribution of participant diary, rulers and thermometers ^k		•			•
Participant diary review by site staff			•			•
Adverse maternal, fetal outcomes		•	•	•	•	•	•	•	•	•
SAE recording		•	•	•	•	•	•	•	•	•	•	•
Concomitant medications ^l	•	•	•	•	•	•	•	•	•	•	•	•
Delivery history ^m									•
Post pregnancy physical examination ^m									•
Laboratory assessmentsⁿ									•
Acceptability questionnaire									•	•		•
Group A immunology subset supplemental procedures (N = 150)	1	2	3	4	5	6	7	8	9	10	11
Humoral immunogenicity sample (serum)							•		•
Cord blood sample									•		•
Breast milk sample (N = 50)										•

pre-dose; pre- and post-dose
^aVisits 7 and 11 for group A immunology subset participants only
^bPP 1 refers to the day of pregnancy completion/termination. Visit 9 (PP 1) should occur on the day of pregnancy completion/termination or within 2 days
^cVisit 10 (PP 43) scheduled to occur at routine 6 week post-partum visit. For women from group A not part of the immunogenicity subset, this visit will be the end of the trial
^dMust be signed before first study-related activity
^eMaternal demographic information to be collected at screening includes date of birth, race/ethnicity, education level, geographical location/residence, occupation, household size (number of persons living in the same home), and international travel history
^fInformation to be collected for medical and obstetric history, physical exams, and vital signs is specified in the protocol
^gUrine dipstick for protein and glucose will be performed at these visits. If results 1 + or greater, then additional work-up for pre-eclampsia or gestational diabetes may be warranted
^hUltrasound not required at visit 2 if screening (visit 1) ultrasound completed within past 10 days and no other indication for ultrasound
ⁱInvestigator must check for acute illness or body temperature ≥ 38.0 °C at the time of vaccination. In such cases, the participant may be vaccinated at later time point
^jParticipants will be closely observed for a minimum of 30 min post-vaccination
^kIn all women of group A, solicited AEs (reactogenicity) and unsolicited AEs will be assessed 7 days post each dose and 28 post each dose respectively
^lIncludes any medical treatment/medications given to the mother during delivery (e.g., antibiotic prophylaxis)-specifying names of medications administered
^mInformation to be collected for delivery history and post-pregnancy examination is specified in the protocol
ⁿAny routine laboratory assessment performed at time of delivery and other laboratory tests as medically indicated
^oNot required if participant is not pregnant
^pIn case pregnancy completion/termination in a group A pregnant woman occurs prior to receipt of dose 2, visits 9 and 10 should be performed: visit 10 being relative to visit 9 (2 day window). Visit 5 (dose 2 vaccination with a window of – 14 days, + 28 days) should in this case be performed after visit 9, with visits 6 and 8 being relative to actual dose 2 receipt (visit 5). All of these visits should be captured in RedCap cloud in addition to source documentation. Reactogenicity data (diary completion) should still be performed following dose 2 for group A women that have a pregnancy completion/termination prior to receipt of dose 2

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ISSN: 1745-6215

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