Trial Outcomes & Findings for Study of BBIL's ROTAVAC® and ROTAVAC 5CM Vaccines in Zambia (NCT NCT03602053)

NCT ID: NCT03602053

Last Updated: 2020-12-19

Results Overview

GMC of serum anti-rotavirus IgA antibodies as measured by enzyme linked immunosorbent assay (ELISA) using WC3 (heterologous to vaccine strain) as the viral lysate. WC3 strain of rotavirus used in the ELISA assay was heterologous to the 116E strain contained in the vaccines ROTAVAC 5D® and ROTAVAC®.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 450 participants
• Primary outcome timeframe: 28 day after last dose of the study vaccine
• Results posted on: 2020-12-19

Participant Flow

Participant milestones

Measure	ROTAVAC 5D® ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® Rotarix® administered at 6 and 10 weeks of age.
Overall Study STARTED	150	150	150
Overall Study COMPLETED	131	132	139
Overall Study NOT COMPLETED	19	18	11

Reasons for withdrawal

Measure	ROTAVAC 5D® ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® Rotarix® administered at 6 and 10 weeks of age.
Overall Study Withdrawal by Subject	7	9	7
Overall Study Lost to Follow-up	5	6	0
Overall Study Protocol Violation	3	0	4
Overall Study Physician Decision	1	0	0
Overall Study migration	2	3	0
Overall Study Other	1	0	0

Baseline Characteristics

Study of BBIL's ROTAVAC® and ROTAVAC 5CM Vaccines in Zambia

Baseline characteristics by cohort

Measure	ROTAVAC 5D® n=150 Participants ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® n=150 Participants ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® n=150 Participants Rotarix® administered at 6 and 10 weeks of age.	Total n=450 Participants Total of all reporting groups
Age, Continuous	6.56 weeks STANDARD_DEVIATION 0.477 • n=5 Participants	6.50 weeks STANDARD_DEVIATION 0.473 • n=7 Participants	6.60 weeks STANDARD_DEVIATION 0.491 • n=5 Participants	6.55 weeks STANDARD_DEVIATION 0.475 • n=4 Participants
Sex: Female, Male Female	66 Participants n=5 Participants	77 Participants n=7 Participants	66 Participants n=5 Participants	209 Participants n=4 Participants
Sex: Female, Male Male	84 Participants n=5 Participants	73 Participants n=7 Participants	84 Participants n=5 Participants	241 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	150 Participants n=5 Participants	150 Participants n=7 Participants	150 Participants n=5 Participants	450 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment Zambia	150 participants n=5 Participants	150 participants n=7 Participants	150 participants n=5 Participants	450 participants n=4 Participants

PRIMARY outcome

Timeframe: 28 day after last dose of the study vaccine

Population: The analysis was performed on Per Protocol Population

GMC of serum anti-rotavirus IgA antibodies as measured by enzyme linked immunosorbent assay (ELISA) using WC3 (heterologous to vaccine strain) as the viral lysate. WC3 strain of rotavirus used in the ELISA assay was heterologous to the 116E strain contained in the vaccines ROTAVAC 5D® and ROTAVAC®.

Outcome measures

Measure	ROTAVAC 5D® n=128 Participants ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® n=124 Participants ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® Rotarix® administered at 6 and 10 weeks of age.
Geometric Mean Concentration Using WC3 as the Viral Lysate	18.1 U/ml Interval 13.7 to 24.0	14.0 U/ml Interval 10.4 to 18.8	—

SECONDARY outcome

Timeframe: within 30 minutes' post-vaccination.

Population: The analysis was performed on Safety Population

Percentage of participants reporting immediate adverse events after each vaccination

Outcome measures

Measure	ROTAVAC 5D® n=150 Participants ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® n=150 Participants ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® n=150 Participants Rotarix® administered at 6 and 10 weeks of age.
Immediate Adverse Events	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 7 day period after each vaccination.

Population: The analysis was performed on Safety Population

Percentage of participants reporting solicited post-vaccination reactogenicity (fever, diarrhea, vomiting, decreased appetite, irritability, decreased activity level)

Outcome measures

Measure	ROTAVAC 5D® n=146 Participants ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® n=144 Participants ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® n=146 Participants Rotarix® administered at 6 and 10 weeks of age.
Solicited Adverse Events Diarrhea	15 Participants	11 Participants	8 Participants
Solicited Adverse Events Vomiting	14 Participants	14 Participants	15 Participants
Solicited Adverse Events Decreased appetite	53 Participants	44 Participants	44 Participants
Solicited Adverse Events Decreased activity level	62 Participants	66 Participants	55 Participants
Solicited Adverse Events Irritability	105 Participants	109 Participants	101 Participants
Solicited Adverse Events Any Solicited AEs	138 Participants	136 Participants	129 Participants
Solicited Adverse Events Fever	110 Participants	109 Participants	100 Participants

SECONDARY outcome

Timeframe: From first vaccination through 4 weeks after the last vaccination.

Population: The analysis was performed on Safety Population

Percentage of participants reporting unsolicited AEs at a rate >5%.

Outcome measures

Measure	ROTAVAC 5D® n=137 Participants ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® n=139 Participants ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® n=142 Participants Rotarix® administered at 6 and 10 weeks of age.
Unsolicited Adverse Events Any Unsolicited AEs	93 Participants	95 Participants	81 Participants
Unsolicited Adverse Events Conjunctivitis	10 Participants	10 Participants	6 Participants
Unsolicited Adverse Events Rhinitis	21 Participants	12 Participants	10 Participants
Unsolicited Adverse Events Upper respiratory tract infection	52 Participants	46 Participants	39 Participants
Unsolicited Adverse Events Diarrhoea	18 Participants	17 Participants	11 Participants

SECONDARY outcome

Timeframe: From first vaccination through 4 weeks after the last vaccination of each study participant. Immunogenicity

Population: The analysis was performed on Safety Population

Percentage of participants reporting SAEs

Outcome measures

Measure	ROTAVAC 5D® n=137 Participants ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® n=139 Participants ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® n=142 Participants Rotarix® administered at 6 and 10 weeks of age.
Serious Adverse Events Any SAEs	2 Participants	1 Participants	3 Participants
Serious Adverse Events Diarrhoea	1 Participants	0 Participants	0 Participants
Serious Adverse Events Bronchiolitis	1 Participants	0 Participants	2 Participants
Serious Adverse Events Sepsis	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 28 days after last dose of study vaccine.

Population: The analysis was performed on Per Protocol Population

Seroconversion is defined as a post-vaccination serum anti-rotavirus IgA antibody concentration of at least 20 U/mL if a baseline concentration is < 20 U/mL or a post-vaccination serum anti-rotavirus IgA antibody concentration of ≥ 2-fold baseline level if a baseline concentration is ≥ 20 U/mL.

WC3 strain of rotavirus used in the ELISA assay was heterologous to the 116E strain contained in the vaccines ROTAVAC® and ROTAVAC 5D®.

Outcome measures

Measure	ROTAVAC 5D® n=128 Participants ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® n=124 Participants ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® n=136 Participants Rotarix® administered at 6 and 10 weeks of age.
Seroconversion Rate in Each of the Three Arms as Measured by ELISA Using WC3 as the Viral Lysate	52 Participants	41 Participants	50 Participants

SECONDARY outcome

Timeframe: 28 days after last dose of study vaccine

Population: Analysis was performed on the Total Vaccinated Cohort.

Seropositivity is defined as serum anti-rotavirus IgA antibody concentration ≥ 20 U/mL. WC3 strain of rotavirus used in the ELISA assay was heterologous to the 116E strain contained in the vaccines ROTAVAC® and ROTAVAC 5D®.

Outcome measures

Measure	ROTAVAC 5D® n=128 Participants ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® n=124 Participants ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® n=136 Participants Rotarix® administered at 6 and 10 weeks of age.
Seropositivity Rate in Each of the Three Vaccine Arms as Measured by ELISA Using WC3 as the Viral Lysate	54 Participants	42 Participants	52 Participants

SECONDARY outcome

Timeframe: 28 days after last dose of study vaccine

Population: The analysis was performed on Per Protocol Population

Seroresponse will be assessed as a four-fold, three-fold and two- fold rise in antibody concentration from baseline. Seroresponse will be assessed as a four-fold, three-fold and two-fold rise in antibody concentration from baseline. WC3 strain of rotavirus used in the ELISA assay was heterologous to the 116E strain contained in the vaccines ROTAVAC® and ROTAVAC 5D®.

Outcome measures

Measure	ROTAVAC 5D® n=128 Participants ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® n=124 Participants ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® n=136 Participants Rotarix® administered at 6 and 10 weeks of age.
Seroresponse Rate in Each of the Three Vaccine Arms as Measured by ELISA Using WC3 as the Viral Lysate Seroresponse rate- Two-fold rise	79 Participants	65 Participants	74 Participants
Seroresponse Rate in Each of the Three Vaccine Arms as Measured by ELISA Using WC3 as the Viral Lysate Seroresponse rate- Three-fold rise	71 Participants	55 Participants	66 Participants
Seroresponse Rate in Each of the Three Vaccine Arms as Measured by ELISA Using WC3 as the Viral Lysate Seroresponse rate- Four-fold rise	61 Participants	49 Participants	58 Participants

SECONDARY outcome

Timeframe: At 28 days after last dose of study vaccine in reference to baseline.

Population: The analysis was performed on Per Protocol Population

GMFR in each of the ROTAVAC 5D®, ROTAVAC® and Rotarix® vaccine arms. WC3 strain of rotavirus used in the ELISA assay was heterologous to the 116E strain contained in the vaccines ROTAVAC® and ROTAVAC 5D®.

Outcome measures

Measure	ROTAVAC 5D® n=128 Participants ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® n=124 Participants ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® n=136 Participants Rotarix® administered at 6 and 10 weeks of age.
Geometric Mean Fold Rise (GMFR) in Each of the Three Vaccine Arms as Measured by ELISA Using WC3 as the Viral Lysate	4.6 Fold rise Interval 3.5 to 6.1	3.6 Fold rise Interval 2.7 to 4.9	3.8 Fold rise Interval 2.9 to 4.9

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after the last dose of a study vaccine.

Population: The analysis was performed on Per Protocol Population

GMCs of serum anti-rotavirus IgA antibodies in each of the three vaccine arms. 89-12 strain of Rotavirus used in the ELISA assay was homologous to Rotarix® and was heterologous to the strain contained in ROTAVAC® and ROTAVAC 5D®.

Outcome measures

Measure	ROTAVAC 5D® n=50 Participants ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® n=50 Participants ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® n=50 Participants Rotarix® administered at 6 and 10 weeks of age.
Geometric Mean Concentrations Using Strain 89-12 as the Viral Lysate	20.6 Au/ml Interval 12.4 to 34.1	19.2 Au/ml Interval 11.0 to 33.5	38.0 Au/ml Interval 20.5 to 70.6

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days after the last dose of a study vaccine.

Population: The analysis was performed on Per Protocol Population

Seroconversion rate in three vaccine arms. 89-12 strain of Rotavirus used in the ELISA assay was homologous to Rotarix® and was heterologous to the strain contained in ROTAVAC® and ROTAVAC 5D®.

Outcome measures

Measure	ROTAVAC 5D® n=50 Participants ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® n=50 Participants ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® n=50 Participants Rotarix® administered at 6 and 10 weeks of age.
Seroconversion Using Strain 89-12 as the Viral Lysate	24 Participants	18 Participants	26 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: at baseline and 28 days after last dose of study vaccine

Population: The analysis was performed on Per Protocol Population

Seropositivity rate in three vaccine arms. 89-12 strain of Rotavirus used in the ELISA assay was homologous to Rotarix® and was heterologous to the strain contained in ROTAVAC® and ROTAVAC 5D®.

Outcome measures

Measure	ROTAVAC 5D® n=50 Participants ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® n=50 Participants ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® n=50 Participants Rotarix® administered at 6 and 10 weeks of age.
Seropositivity Using Strain 89-12 as the Viral Lysate	25 Participants	18 Participants	27 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: at 28 days after last dose of study vaccine in reference to baseline.

Population: The analysis was performed on Per Protocol Population

GMFR in the three vaccine arms. 89-12 strain of Rotavirus used in the ELISA assay was homologous to Rotarix® and was heterologous to the strain contained in ROTAVAC® and ROTAVAC 5D®.

Outcome measures

Measure	ROTAVAC 5D® n=50 Participants ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® n=50 Participants ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® n=50 Participants Rotarix® administered at 6 and 10 weeks of age.
Geometric Mean Fold Rise (GMFR) Using Strain 89-12 as the Viral Lysate	4.8 Fold rise Interval 3.0 to 7.8	4.9 Fold rise Interval 2.8 to 8.7	8.8 Fold rise Interval 4.7 to 16.4

Adverse Events

ROTAVAC 5D®

Serious events: 2 serious events

Other events: 93 other events

Deaths: 0 deaths

ROTAVAC®

Serious events: 1 serious events

Other events: 95 other events

Deaths: 0 deaths

Rotarix®

Serious events: 3 serious events

Other events: 81 other events

Deaths: 0 deaths

Serious adverse events

Measure	ROTAVAC 5D® n=137 participants at risk ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® n=139 participants at risk ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® n=142 participants at risk Rotarix® administered at 6 and 10 weeks of age.
Gastrointestinal disorders Diarrhoea	0.73% 1/137 • Number of events 1 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.	0.00% 0/139 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.	0.00% 0/142 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.
Infections and infestations Bronchiolitis	0.73% 1/137 • Number of events 1 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.	0.00% 0/139 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.	1.4% 2/142 • Number of events 2 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.
Infections and infestations Sepsis	0.00% 0/137 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.	0.72% 1/139 • Number of events 1 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.	0.70% 1/142 • Number of events 1 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.

Other adverse events

Measure	ROTAVAC 5D® n=137 participants at risk ROTAVAC 5D® administered at 6, 10 and 14 weeks of age.	ROTAVAC® n=139 participants at risk ROTAVAC® administered at 6, 10 and 14 weeks of age.	Rotarix® n=142 participants at risk Rotarix® administered at 6 and 10 weeks of age.
Infections and infestations Conjuntivities	7.3% 10/137 • Number of events 10 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.	7.2% 10/139 • Number of events 10 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.	4.2% 6/142 • Number of events 6 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.
Infections and infestations Rhinitis	15.3% 21/137 • Number of events 22 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.	8.6% 12/139 • Number of events 12 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.	7.0% 10/142 • Number of events 10 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.
Infections and infestations Respiratory Tract Infection	16.1% 22/137 • Number of events 23 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.	18.7% 26/139 • Number of events 27 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.	10.6% 15/142 • Number of events 16 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.
Infections and infestations Upper Respiratory Tract Infection	38.0% 52/137 • Number of events 71 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.	33.1% 46/139 • Number of events 56 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.	27.5% 39/142 • Number of events 43 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.
Infections and infestations Diarrhoea	13.1% 18/137 • Number of events 18 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.	12.2% 17/139 • Number of events 18 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.	7.7% 11/142 • Number of events 11 • Immediate Adverse Event within 30 mins post vaccination. Solicited adverse events for 7 days post vaccination. Unsolicited Adverse events for 28 days after each vaccination. Serious Adverse Events.

Additional Information

Dr Niraj Rathi, MD; Senior Medical Officer

PATH

Phone: +91 11 4064 0000

Email: nrathi@path.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place