A Phase 3 interventional study of Live Japanese encephalitis vaccine SA 14-14-2 (LJEV) and Measles Vaccine (MV) in Encephalitis, Japanese B, sponsored by PATH. Completed at 1 site in Philippines. Open to participants aged 8 Months to 11 Months, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-03-10.
Sponsored by PATH · Phase 3, Interventional, and Prevention
This study will determine whether it is safe and effective to administer Japanese encephalitis (JE) live attenuated SA 14-14-2 vaccine at the same time as measles vaccine. If it is found to be safe, it will pave the way for use in routine vaccination programs. The hypothesis is that children who receive JE live attenuated SA 14-14-2 vaccine and measles vaccine at the same time are protected against these diseases at the same level as those who receive the vaccines at different intervals.
Japanese encephalitis is the leading cause of viral neurological disease and disability in Asia. The severity of sequelae, together with the volume of cases, make JE the most important cause of viral encephalitis in the world. Approximately 3 billion people-including 700 million children-live in Asian areas at risk for JE. JE most commonly infects children between the ages of 1 and 15 years, and can also infect adults in areas where the virus is newly introduced. More than 50,000 cases are reported annually and cause an estimated 10,000 to 15,000 deaths. This figure is believed to represent only a small proportion of the disease burden that actually exists.
An effective vaccine has existed since 1941, but has not reached the poorest countries in Asia. During the 60 years that the vaccine has been available, JE has infected an estimated 10.5 million children, resulting in more than 3 million deaths and more than 4 million children living with long-term disabilities. Control of this disease has been limited due to poor disease surveillance, a limited and unstable vaccine supply, lack of guidance and programmatic support for immunization, and limited advocacy.
A successful vaccine should be safe, efficacious, affordable, administered in a single dose, and easily incorporated into the routine Expanded Programmes on Immunization (EPI) programs. This study will help ensure the safety of SA 14-14-2 simultaneously administered with measles vaccine, paving the way for its use in routine EPI programs. If this candidate becomes widely available, it will drastically increase the feasibility of routine JE immunization in Asia, reducing the devastating death and disability caused by this disease. In addition to impacting low-income countries, the vaccine will allow countries that purchase vaccine-such as Thailand, Vietnam, Sri Lanka, and India-to recover health care dollars, improve their present programs, and address other unmet health care needs.
77 studies on the registry are indexed under Encephalitis, Japanese; 4 are open to participants now.
This study's enrollment of 600 is above the median of 278 across 69 interventional studies indexed under Encephalitis, Japanese.
Browse Encephalitis, Japanese studies →PATH is the lead sponsor of 111 studies on the registry; 7 are open to participants now.
Of its 10 completed or terminated interventional studies of FDA-regulated products, 10 (100%) have results posted.
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Exclusion Criteria:
Received one dose of Live Japanese encephalitis vaccine SA 14-14-2 (LJEV) at 8 months of age, and one dose of measles vaccine (MV) one month later.
Biological: Live Japanese encephalitis vaccine SA 14-14-2 (LJEV) · Biological: Measles Vaccine (MV)
Received one dose of Live Japanese encephalitis vaccine SA 14-14-2 (LJEV) concurrently with one dose of measles vaccine (MV) at 9 months of age.
Biological: Live Japanese encephalitis vaccine SA 14-14-2 (LJEV) · Biological: Measles Vaccine (MV)
Received one dose of measles vaccine (MV) at 9 months of age, followed by one dose of Live Japanese encephalitis vaccine SA 14-14-2 (LJEV) one month later.
Biological: Live Japanese encephalitis vaccine SA 14-14-2 (LJEV) · Biological: Measles Vaccine (MV)
Live Japanese encephalitis vaccine SA 14-14-2 (LJEV) is lyophilized powder that looks like a milky-white crisp cake. After reconstitution, it turns into a transparent orange red liquid. Its container is a vial. It is stored and transported between 2°C to 8°C and protected from light. Each single human dose is 0.5 ml containing not less than 5.4 log particle flux unit (PFU) of live Japanese Encephalitis (JE) virus. The 0.5ml injection is delivered subcutaneously via auto-disable syringe. Lot number 200411129-3 manufactured by Chengdu Institute of Biological Products (CDIBP), Chengdu, China.
The Serum Institute of India (SII) measles vaccine provided routinely in the Expanded Program on Immunization (EPI) of the Philippines was the measles vaccine provided to the study participants. The vaccine met the requirements of the World Health Organization (WHO). SII measles vaccine contained live attenuated (freeze-dried) Edmonston-Zagreb strain measles virus propagated on human diploid cells (HDC). Each single human dose when reconstituted in a volume of 0.5 ml contains no less than 1000 Cell culture infectious dose 50% (CCID50) of live virus particles. SII measles vaccine is presented as a yellowish-white dry cake. The vaccine should be reconstituted with the diluent supplied (sterile water for injection). A sterile disposable syringe and needle are supplied separately. The 0.5ml injection is delivered subcutaneously via auto-disable syringe. Lot number 2979.
Percentage of Participants With Seroprotection for Measles 4 Weeks After Vaccination
Seroprotection after measles vaccination was defined as a measles antibody titer ≥ 120 mIU/mL. Measles immunoglobulin G (IgG) antibody was determined using the Enzygnost® Anti-Measles Virus/IgG enzyme-linked immunosorbent assay(ELISA) assay from Siemens, Marburg, Germany.
Time frame: Day 0 (before vaccination) and Day 28 (4 weeks after measles vaccination)
Percentage of Participants With Seroprotection for Japanese Encephalitis 4 Weeks After Vaccination
Seroprotection after LJEV was defined as at least 1:10 dilution as recommended by the World Health Organization (WHO). JE antibody titers were determined by a plaque reduction neutralization test (PRNT).
Time frame: Day 0 (before vaccination) and Day 28 (4 weeks after LJEV vaccination)
Geometric Mean Concentration (GMC) of Measles Antibodies After Vaccination
Measured using the Enzygnost® Anti-Measles Virus/IgG ELISA assay from Siemens, Marburg, Germany.
Time frame: Day 0 (before vaccination) and Day 28 (4 weeks after measles vaccination)
Geometric Mean Titer (GMT) of Japanese Encephalitis Antibodies After Vaccination
Assayed by plaque reduction neutralization test (PRNT).
Time frame: Day 0 (before vaccination) and Day 28 (4 weeks after LJEV vaccination)
Number of Participants Experiencing Local and Systemic Reactogenicity After Receiving Live Attenuated Japanese Encephalitis Vaccine (LJEV)
Local reactions included erythema, pain, swelling, or induration. Systemic reactions included loss of appetite, crying, diarrhea, drowsiness, insomnia, irritability, vomiting, or fever. The parents of the participants recorded all local reactions and systemic events on an individual safety diary form.
Time frame: Up to 7 days after LJEV administration
Number of Participants Experiencing Local and Systemic Reactogenicity After Receiving Measles Vaccine
Local reactions included erythema, pain, swelling, and induration. Systemic reactions included loss of appetite, crying, diarrhea, drowsiness, insomnia, irritability, and vomiting. The parents of the participants recorded all local reactions and systemic events on an individual safety diary form.
Time frame: Up to 7 days after measles vaccination
Number of Participants Experiencing Unsolicited Adverse Events (AE)
Time frame: Up to 7 days post-vaccination
| Milestone | LJEV Then MV | LJEV and MV | MV Then LJEV |
|---|---|---|---|
| Started | 100 | 250 | 250 |
| Received ljev | 100 | 236 | 224 |
| Received measles vaccine | 97 | 236 | 235 |
| Completed | 98 | 235 | 222 |
| Not completed | 2 | 15 | 28 |
| Withdrew: Withdrawal by subject | 1 | 10 | 6 |
| Withdrew: Migration from study area | 1 | 3 | 14 |
| Withdrew: Miscellaneous | 0 | 2 | 2 |
| Withdrew: Adverse event | 0 | 0 | 1 |
| Withdrew: Physician decision | 0 | 0 | 2 |
| Withdrew: Lost to follow-up | 0 | 0 | 3 |
Seroprotection after measles vaccination was defined as a measles antibody titer ≥ 120 mIU/mL. Measles immunoglobulin G (IgG) antibody was determined using the Enzygnost® Anti-Measles Virus/IgG enzyme-linked immunosorbent assay(ELISA) assay from Siemens, Marburg, Germany.
| percentage of participants | LJEV Then MV | LJEV and MV | MV Then LJEV |
|---|---|---|---|
| Day 0 | 1.1 (0.0 to 6.2) | 0.0 (0.0 to 1.7) | 0.0 (0.0 to 2.1) |
| Day 28 | 88.6 (80.1 to 94.4) | 91.8 (87.3 to 95.1) | 86.5 (80.6 to 91.2) |
Seroprotection after LJEV was defined as at least 1:10 dilution as recommended by the World Health Organization (WHO). JE antibody titers were determined by a plaque reduction neutralization test (PRNT).
| percentage of participants | LJEV Then MV | LJEV and MV | MV Then LJEV |
|---|---|---|---|
| Day 0 | 3.4 (0.7 to 9.6) | 5.4 (2.8 to 9.3) | 6.1 (3.1 to 10.7) |
| Day 28 | 92.1 (84.3 to 96.7) | 90.5 (85.9 to 94.1) | 90.6 (85.3 to 94.4) |
Measured using the Enzygnost® Anti-Measles Virus/IgG ELISA assay from Siemens, Marburg, Germany.
| mIU/mL | LJEV Then MV | LJEV and MV | MV Then LJEV |
|---|---|---|---|
| Day 0 | 12.8 (10.2 to 16.2) | 7.4 (6.3 to 8.8) | 7.0 (5.8 to 8.5) |
| Day 28 | 318.9 (273.0 to 372.6) | 301.9 (269.0 to 338.9) | 262.5 (222.2 to 310.2) |
Assayed by plaque reduction neutralization test (PRNT).
| titer | LJEV Then MV | LJEV and MV | MV Then LJEV |
|---|---|---|---|
| Day 0 | 5.7 (4.9 to 6.5) | 5.7 (5.2 to 6.1) | 5.9 (5.3 to 6.6) |
| Day 28 | 202.8 (140.5 to 292.9) | 155.0 (123.5 to 194.5) | 139.4 (109.5 to 177.5) |
Local reactions included erythema, pain, swelling, or induration. Systemic reactions included loss of appetite, crying, diarrhea, drowsiness, insomnia, irritability, vomiting, or fever. The parents of the participants recorded all local reactions and systemic events on an individual safety diary form.
| Participants | LJEV Then MV | LJEV and MV | MV Then LJEV |
|---|---|---|---|
| Local reactions: any | 27 | 53 | 27 |
| Local reactions: mild | 19 | 48 | 22 |
| Local reactions: moderate | 8 | 5 | 5 |
| Local reactions: severe | 0 | 0 | 0 |
| Systemic reactions: any | 58 | 97 | 88 |
| Systemic reaction: mild | 34 | 53 | 56 |
| Systemic reaction: moderate | 22 | 37 | 30 |
| Systemic reaction: severe | 2 | 7 | 2 |
| Fever: any | 24 | 52 | 57 |
| Fever: 37.5-38.6°C | 18 | 38 | 47 |
| Fever: 38.7-39.9°C | 6 | 14 | 10 |
| Fever: ≥ 40°C | 0 | 0 | 0 |
Local reactions included erythema, pain, swelling, and induration. Systemic reactions included loss of appetite, crying, diarrhea, drowsiness, insomnia, irritability, and vomiting. The parents of the participants recorded all local reactions and systemic events on an individual safety diary form.
| Participants | LJEV Then MV | LJEV and MV | MV Then LJEV |
|---|---|---|---|
| Local reactions: any | 19 | 44 | 61 |
| Local reactions: mild | 15 | 42 | 50 |
| Local reactions: moderate | 4 | 2 | 11 |
| Local reactions: severe | 0 | 0 | 0 |
| Systemic reactions: any | 49 | 97 | 122 |
| Systemic reaction: mild | 31 | 53 | 77 |
| Systemic reaction: moderate | 13 | 37 | 42 |
| Systemic reaction: severe | 5 | 7 | 3 |
| Fever: any | 31 | 52 | 64 |
| Fever: 37.5-38.6°C | 21 | 38 | 52 |
| Fever: 38.7-39.9°C | 10 | 14 | 12 |
| Fever: ≥ 40°C | 0 | 0 | 0 |
| Participants | LJEV Then MV | LJEV and MV | MV Then LJEV |
|---|---|---|---|
| Any Adverse Event | 35 | 43 | 79 |
| Related adverse event | 0 | 4 | 2 |
| Serious adverse event | 2 | 0 | 3 |
Collected over 1 month for serious adverse events and 7 days for non-serious adverse events. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| LJEV Then MV | 0/100 (0%) | 5/100 (5%) | 34/100 (34%) |
| LJEV and MV | 0/236 (0%) | 0/236 (0%) | 43/236 (18.2%) |
| MV Then LJEV | 0/235 (0%) | 7/235 (3%) | 78/235 (33.2%) |
| Event | LJEV Then MV | LJEV and MV | MV Then LJEV |
|---|---|---|---|
| Acute GastroenteritisGastrointestinal disorders | 2/100 | 0/236 | 1/235 |
| AmoebiasisGastrointestinal disorders | 1/100 | 0/236 | 2/235 |
| Urinary tract infectionRenal and urinary disorders | 1/100 | 0/236 | 1/235 |
| PneumoniaInfections and infestations | 1/100 | 0/236 | 0/235 |
| Animal biteInjury, poisoning and procedural complications | 0/100 | 0/236 | 1/235 |
| Bronchial AsthmaRespiratory, thoracic and mediastinal disorders | 0/100 | 0/236 | 1/235 |
| Complex Febrile SeizureNervous system disorders | 0/100 | 0/236 | 1/235 |
| Event | LJEV Then MV | LJEV and MV | MV Then LJEV |
|---|---|---|---|
| Upper respiratory tract infectionRespiratory, thoracic and mediastinal disorders | 14/100 | 18/236 | 42/235 |
| Acute gastroenteritisGastrointestinal disorders | 8/100 | 7/236 | 8/235 |
| Acute rhinitisRespiratory, thoracic and mediastinal disorders | 6/100 | 6/236 | 10/235 |
| Acute bronchitisInfections and infestations | 4/100 | 1/236 | 5/235 |
| Systemic viral infectionInfections and infestations | 4/100 | 0/236 | 2/235 |
| DermatitisSkin and subcutaneous tissue disorders | 0/100 | 3/236 | 0/235 |
| FuruncleSkin and subcutaneous tissue disorders | 0/100 | 3/236 | 1/235 |
| Bacterial conjunctivitisInfections and infestations | 1/100 | 0/236 | 0/235 |
| StomatitisGastrointestinal disorders | 1/100 | 0/236 | 1/235 |
| Urinary tract infectionInfections and infestations | 1/100 | 0/236 | 1/235 |
The Safety population included all participants who received at least 1 vaccination.
| Age, Continuous(months) | LJEV Then MV | LJEV and MV | MV Then LJEV | Total |
|---|---|---|---|---|
| Mean | 7.9 ± 0.3 | 8.9 ± 0.3 | 8.9 ± 0.3 | 8.7 ± 0.5 |
| Sex: Female, Male(Participants) | LJEV Then MV | LJEV and MV | MV Then LJEV | Total |
|---|---|---|---|---|
| Female | 48 | 108 | 128 | 284 |
| Male | 52 | 128 | 107 | 287 |
| Weight(kilograms) | LJEV Then MV | LJEV and MV | MV Then LJEV | Total |
|---|---|---|---|---|
| Mean | 7.9 ± 1.0 | 8.0 ± 1.0 | 8.1 ± 1.0 | 8.0 ± 1.0 |
| Height(centimeters) | LJEV Then MV | LJEV and MV | MV Then LJEV | Total |
|---|---|---|---|---|
| Mean | 66.3 ± 2.6 | 67.6 ± 2.7 | 67.7 ± 2.6 | 67.4 ± 2.7 |
This study is completed, as verified in Sep 2018. You cannot join it, but the record below documents what was studied.
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