Prophylaxis for the Measles Infection
Conditions
Brief summary
This is a phase I, open-label, randomized study in healthy adults. Eligible subjects will be given single dose of either Dry Powdered Measles Vaccine (PMV) by Puffhaler® device, Dry PMV by SoloventTM device or licensed measles vaccine by subcutaneous route (SMV). Subjects will be followed for 180 days for safety.
Detailed description
This is a phase I, open-label, randomized study in healthy adults. Eligible subjects will be given single dose of either Dry Powdered Measles Vaccine (PMV) by Puffhaler® device, Dry PMV by SoloventTM device or licensed measles vaccine by subcutaneous route (SMV). Solicited reactions will be assessed for first 14 days after vaccination and unsolicited adverse events will be assessed till 84 days after vaccination. Subjects will be followed for 180 days for any SAEs.
Interventions
BIOLOGICALPMV via Puffhaler® device
The vaccine will be administered via a Puffhaler® device. A single dose of 10 mg of PMV (dry powder measles vaccine) will be used.
BIOLOGICALPMV via SoloventTM device
The vaccine will be administered via SoloventTM device. A single dose of 10 mg of PMV (dry powder measles vaccine) will be used.
BIOLOGICALLicensed Subcutaneous Measles Vaccine
This is a licensed formulation containing the live attenuated Edmonston Zagreb virus. A single dose of 0.5 ml will be given subcutaneously.
Sponsors
University of Colorado, Boulder
Centers for Disease Control and Prevention
Serum Institute of India Pvt. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Male adults of age of 18-45 years. * Measles immune, as determined by IgG antibody levels. * Healthy as supported by medical history, physical examination and laboratory evaluation on preset parameters. * Signed informed consent for participation in trial and for HIV screening.
Exclusion criteria
* Medical history of immunodeficiency/suppression or subject with history of close contact with immunocompromised/ immunosuppressed person. * Chronic administration of immunosuppressants or other immune modifying agents * Acute febrile illness or suspected measles illness or acute infectious disease * Acute or chronic, clinically significant pulmonary, endocrine, autoimmune, psychiatric, cardiovascular, neurological, hepatic or renal functional abnormality which in the opinion of the investigator, might interfere with the study objectives * History of seizure disorders * Major congenital defects * Thrombocytopenia or known bleeding disorders 8. History of a previous severe allergic reaction * Positive serology for HIV antibody, HCV antibody or Hepatitis B surface antigen * Known hypersensitivity to any component of the study vaccine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Solicited Reactions | Day 14 | Incidence of solicited local and systemic reactions within 14 days of vaccine administration in each group was assessed. |
| Incidence of Unsolicited Adverse Events Within 84 Days | Day 84 | Incidence of unsolicited adverse events for a period of 84 days in each group was assessed. |
| Incidence of Serious Adverse Events (SAEs) and New Onset Chronic Medical Conditions | Day 180 | Incidence of serious adverse events (SAEs) and new onset chronic medical conditions throughout the entire study period of 180 days in each group was assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Subjects in Each Group With Seroconversion for PRNT | Day 28 and Day 84 | The proportion of subjects in each group who show a seroconversion for PRNT on Day 28 and Day 84 was assessed. |
| The Proportion of Subjects in Each Group With Seropositive Anti-Measles IgG Antibodies | Day -7, Day 28 and Day 84 | The proportion of subjects in each group with seropositive anti-Measles IgG antibodies on Day -7, Day 28 and Day 84 was assessed. |
| Geometric Mean Titre (GMT) by PRNT on Day -7, 28 and 84 | Day -7, Day 28 and Day 84 | Geometric Mean Titre by Plaque Reduction Neutralization Test were assessed on Day -7, 28 and 84 at CDC, Atlanta. Titers are expressed as IU/ml. |
| Geometric Mean Concentration (GMC) for Anti-Measles IgG Antibodies | Day -7, Day 28 and Day 84 | Geometric Mean Concentration (GMC) for anti-Measles IgG antibodies were measured on Day -7, Day 28 and Day 84 by ELISA using Trinity ELISA Kits for Measles. |
| The Proportion of Subjects in Each Group With Seroprotective Plaque-reduction Neutralization Test (PRNT) Titre | Day -7, Day 28 and Day 84 | The proportion of subjects in each group with seroprotective plaque-reduction neutralization test (PRNT) titre on Day -7, Day 28 and Day 84 was assessed. |
| The Proportion of Subjects in Each Group With Seroconversion for Serum Anti-Measles IgG | Day 28 and Day 84 | The proportion of subjects in each group who show a seroconversion for serum anti-Measles IgG on Day 28 and Day 84 was assessed. |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PMV Puffhaler® Dry Powdered Measles Vaccine: The vaccine was administered via a Puffhaler® device. A single dose of 10 mg was used.
N=20 | 20 |
| PMV SoloventTM Dry Powdered Measles Vaccine: The vaccine was administered via SoloventTM device. A single dose of 10 mg was used.
N=20 | 20 |
| Subcutaneous Meales Vaccine Licensed Subcutaneous Measles Vaccine: This is a licensed formulation containing the live attenuated Edmonston Zagreb virus. A single dose of 0.5 ml was given subcutaneously.
N=20 | 20 |
| Total | 60 |
Baseline characteristics
| Characteristic | PMV Puffhaler® | PMV SoloventTM | Subcutaneous Meales Vaccine | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 20 Participants | 20 Participants | 60 Participants |
| Age, Continuous | 28 years STANDARD_DEVIATION 7 | 30 years STANDARD_DEVIATION 6 | 28 years STANDARD_DEVIATION 7 | 28.67 years STANDARD_DEVIATION 6.67 |
| Region of Enrollment India | 20 participants | 20 participants | 20 participants | 60 participants |
| Sex/Gender, Customized | 20 Male participants | 20 Male participants | 20 Male participants | 60 Male participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 |
Outcome results
Primary
Incidence of Serious Adverse Events (SAEs) and New Onset Chronic Medical Conditions
Incidence of serious adverse events (SAEs) and new onset chronic medical conditions throughout the entire study period of 180 days in each group was assessed.
Time frame: Day 180
Population: Intention-To-Treat (ITT) Population was used for safety and immunogenicity analysis. ITT population included subjects who had blood drawn to confirm a measles protective titer at Day -7 and met all inclusion/ exclusion criteria and did not receive a vaccine forbidden in the study protocol within the previous 30 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PMV Puffhaler® | Incidence of Serious Adverse Events (SAEs) and New Onset Chronic Medical Conditions | 0 participants |
| PMV SoloventTM | Incidence of Serious Adverse Events (SAEs) and New Onset Chronic Medical Conditions | 0 participants |
| Subcutaneous Meales Vaccine | Incidence of Serious Adverse Events (SAEs) and New Onset Chronic Medical Conditions | 0 participants |
Primary
Incidence of Solicited Reactions
Incidence of solicited local and systemic reactions within 14 days of vaccine administration in each group was assessed.
Time frame: Day 14
Population: Intention-To-Treat (ITT) Population included all subjects who received at least one dose of study vaccine and had at least one post-baseline assessment, regardless of whether they adhered to the study eligibility criteria or whether their study medication administration and study procedure visits are within the protocol-specified windows.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PMV Puffhaler® | Incidence of Solicited Reactions | 0 participants |
| PMV SoloventTM | Incidence of Solicited Reactions | 0 participants |
| Subcutaneous Meales Vaccine | Incidence of Solicited Reactions | 0 participants |
Primary
Incidence of Unsolicited Adverse Events Within 84 Days
Incidence of unsolicited adverse events for a period of 84 days in each group was assessed.
Time frame: Day 84
Population: Intention-To-Treat (ITT) Population was used for safety analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PMV Puffhaler® | Incidence of Unsolicited Adverse Events Within 84 Days | 0 participants |
| PMV SoloventTM | Incidence of Unsolicited Adverse Events Within 84 Days | 0 participants |
| Subcutaneous Meales Vaccine | Incidence of Unsolicited Adverse Events Within 84 Days | 0 participants |
Secondary
Geometric Mean Concentration (GMC) for Anti-Measles IgG Antibodies
Geometric Mean Concentration (GMC) for anti-Measles IgG antibodies were measured on Day -7, Day 28 and Day 84 by ELISA using Trinity ELISA Kits for Measles.
Time frame: Day -7, Day 28 and Day 84
Population: Per Protocol (PP) Population was for the Immunogenicity analysis \& included subjects who received a dose of the study vaccine and met all inclusion/ exclusion criteria and complied with study procedures as defined in the study protocol, did not show any major protocol violation and gave baseline (Day -7) and Day 28 immunogenicity blood samples.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| PMV Puffhaler® | Geometric Mean Concentration (GMC) for Anti-Measles IgG Antibodies | Baseline (Day-7) | 0.91 IU/ml |
| PMV Puffhaler® | Geometric Mean Concentration (GMC) for Anti-Measles IgG Antibodies | Day 84 | 1.71 IU/ml |
| PMV Puffhaler® | Geometric Mean Concentration (GMC) for Anti-Measles IgG Antibodies | Day 28 | 1.46 IU/ml |
| PMV SoloventTM | Geometric Mean Concentration (GMC) for Anti-Measles IgG Antibodies | Day 28 | 1.49 IU/ml |
| PMV SoloventTM | Geometric Mean Concentration (GMC) for Anti-Measles IgG Antibodies | Baseline (Day-7) | 1.31 IU/ml |
| PMV SoloventTM | Geometric Mean Concentration (GMC) for Anti-Measles IgG Antibodies | Day 84 | 2.14 IU/ml |
| Subcutaneous Meales Vaccine | Geometric Mean Concentration (GMC) for Anti-Measles IgG Antibodies | Baseline (Day-7) | 0.86 IU/ml |
| Subcutaneous Meales Vaccine | Geometric Mean Concentration (GMC) for Anti-Measles IgG Antibodies | Day 84 | 1.45 IU/ml |
| Subcutaneous Meales Vaccine | Geometric Mean Concentration (GMC) for Anti-Measles IgG Antibodies | Day 28 | 1.03 IU/ml |
Secondary
Geometric Mean Titre (GMT) by PRNT on Day -7, 28 and 84
Geometric Mean Titre by Plaque Reduction Neutralization Test were assessed on Day -7, 28 and 84 at CDC, Atlanta. Titers are expressed as IU/ml.
Time frame: Day -7, Day 28 and Day 84
Population: Per Protocol (PP) Population was for the Immunogenicity analysis \& included subjects who received a dose of the study vaccine and met all inclusion/ exclusion criteria and complied with study procedures as defined in the study protocol, did not show any major protocol violation and gave baseline (Day -7) and Day 28 immunogenicity blood samples.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| PMV Puffhaler® | Geometric Mean Titre (GMT) by PRNT on Day -7, 28 and 84 | Day 28 | 2626.5 IU/ml |
| PMV Puffhaler® | Geometric Mean Titre (GMT) by PRNT on Day -7, 28 and 84 | Baseline (Day -7) | 1914.3 IU/ml |
| PMV Puffhaler® | Geometric Mean Titre (GMT) by PRNT on Day -7, 28 and 84 | Day 84 | 1789.5 IU/ml |
| PMV SoloventTM | Geometric Mean Titre (GMT) by PRNT on Day -7, 28 and 84 | Day 28 | 1569.1 IU/ml |
| PMV SoloventTM | Geometric Mean Titre (GMT) by PRNT on Day -7, 28 and 84 | Baseline (Day -7) | 1479.5 IU/ml |
| PMV SoloventTM | Geometric Mean Titre (GMT) by PRNT on Day -7, 28 and 84 | Day 84 | 1526.5 IU/ml |
| Subcutaneous Meales Vaccine | Geometric Mean Titre (GMT) by PRNT on Day -7, 28 and 84 | Baseline (Day -7) | 2010.4 IU/ml |
| Subcutaneous Meales Vaccine | Geometric Mean Titre (GMT) by PRNT on Day -7, 28 and 84 | Day 84 | 1152.2 IU/ml |
| Subcutaneous Meales Vaccine | Geometric Mean Titre (GMT) by PRNT on Day -7, 28 and 84 | Day 28 | 1789.7 IU/ml |
Secondary
The Proportion of Subjects in Each Group With Seroconversion for PRNT
The proportion of subjects in each group who show a seroconversion for PRNT on Day 28 and Day 84 was assessed.
Time frame: Day 28 and Day 84
Population: Per Protocol (PP) Population was for the Immunogenicity analysis \& included subjects who received a dose of the study vaccine and met all inclusion/ exclusion criteria and complied with study procedures as defined in the study protocol, did not show any major protocol violation and gave baseline (Day -7) and Day 28 immunogenicity blood samples.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PMV Puffhaler® | The Proportion of Subjects in Each Group With Seroconversion for PRNT | Day 28 | 45 percentage of participants |
| PMV Puffhaler® | The Proportion of Subjects in Each Group With Seroconversion for PRNT | Day 84 | 30 percentage of participants |
| PMV SoloventTM | The Proportion of Subjects in Each Group With Seroconversion for PRNT | Day 84 | 30 percentage of participants |
| PMV SoloventTM | The Proportion of Subjects in Each Group With Seroconversion for PRNT | Day 28 | 25 percentage of participants |
| Subcutaneous Meales Vaccine | The Proportion of Subjects in Each Group With Seroconversion for PRNT | Day 84 | 25 percentage of participants |
| Subcutaneous Meales Vaccine | The Proportion of Subjects in Each Group With Seroconversion for PRNT | Day 28 | 30 percentage of participants |
Secondary
The Proportion of Subjects in Each Group With Seroconversion for Serum Anti-Measles IgG
The proportion of subjects in each group who show a seroconversion for serum anti-Measles IgG on Day 28 and Day 84 was assessed.
Time frame: Day 28 and Day 84
Population: Per Protocol Population was used for the Immunogenicity analysis which included subjects who received a dose of the study vaccine and met all inclusion/ exclusion criteria and complied with study procedures as defined in the study protocol, did not show any major protocol violation and gave baseline (Day -7) and Day 28 blood samples.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PMV Puffhaler® | The Proportion of Subjects in Each Group With Seroconversion for Serum Anti-Measles IgG | at day 28 | 45 percentage of participants |
| PMV Puffhaler® | The Proportion of Subjects in Each Group With Seroconversion for Serum Anti-Measles IgG | at day 84 | 55 percentage of participants |
| PMV SoloventTM | The Proportion of Subjects in Each Group With Seroconversion for Serum Anti-Measles IgG | at day 28 | 20 percentage of participants |
| PMV SoloventTM | The Proportion of Subjects in Each Group With Seroconversion for Serum Anti-Measles IgG | at day 84 | 45 percentage of participants |
| Subcutaneous Meales Vaccine | The Proportion of Subjects in Each Group With Seroconversion for Serum Anti-Measles IgG | at day 28 | 25 percentage of participants |
| Subcutaneous Meales Vaccine | The Proportion of Subjects in Each Group With Seroconversion for Serum Anti-Measles IgG | at day 84 | 35 percentage of participants |
Secondary
The Proportion of Subjects in Each Group With Seropositive Anti-Measles IgG Antibodies
The proportion of subjects in each group with seropositive anti-Measles IgG antibodies on Day -7, Day 28 and Day 84 was assessed.
Time frame: Day -7, Day 28 and Day 84
Population: Per Protocol (PP) Population was for the Immunogenicity analysis \& included subjects who received a dose of the study vaccine and met all inclusion/ exclusion criteria and complied with study procedures as defined in the study protocol, did not show any major protocol violation and gave baseline (Day -7) and Day 28 immunogenicity blood samples.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PMV Puffhaler® | The Proportion of Subjects in Each Group With Seropositive Anti-Measles IgG Antibodies | 100 percentage of participants |
| PMV SoloventTM | The Proportion of Subjects in Each Group With Seropositive Anti-Measles IgG Antibodies | 100 percentage of participants |
| Subcutaneous Meales Vaccine | The Proportion of Subjects in Each Group With Seropositive Anti-Measles IgG Antibodies | 100 percentage of participants |
Secondary
The Proportion of Subjects in Each Group With Seroprotective Plaque-reduction Neutralization Test (PRNT) Titre
The proportion of subjects in each group with seroprotective plaque-reduction neutralization test (PRNT) titre on Day -7, Day 28 and Day 84 was assessed.
Time frame: Day -7, Day 28 and Day 84
Population: Per Protocol (PP) Population was used for the Immunogenicity analysis which included subjects who received a dose of the study vaccine and met all inclusion/ exclusion criteria and complied with study procedures as defined in the study protocol, did not show any major protocol violation and gave baseline (Day -7) and Day 28 blood samples.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PMV Puffhaler® | The Proportion of Subjects in Each Group With Seroprotective Plaque-reduction Neutralization Test (PRNT) Titre | 100 percentage of participants |
| PMV SoloventTM | The Proportion of Subjects in Each Group With Seroprotective Plaque-reduction Neutralization Test (PRNT) Titre | 100 percentage of participants |
| Subcutaneous Meales Vaccine | The Proportion of Subjects in Each Group With Seroprotective Plaque-reduction Neutralization Test (PRNT) Titre | 95 percentage of participants |