| CTRI Number |
CTRI/2020/03/023739 [Registered on: 03/03/2020] Trial Registered Prospectively |
| Last Modified On: |
08/08/2022 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Vaccine |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
Malaria vaccine study in healthy Indian adult males. |
|
Scientific Title of Study
|
A Phase I, randomized, controlled, dose escalating, single blind, clinical trial to assess the safety, tolerability and immunogenicity of Bivalent (JAIVAC-2: PfMSPFu24 +PfF2/ Alhydrogel) P. falciparum malaria vaccine in malaria naive healthy Indian adult males |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| MVDP/Falciparum/1/17/01, Version No. 02; Date: 22 Apr 2019 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Anil K MBBS MD |
| Designation |
Principal Investigator |
| Affiliation |
Syngene International Ltd |
| Address |
Syngene International Ltd
Human Pharmacology Unit Tower 1 Ground Floor Semicon Park Electronics City Phase 2 Hosur Main Road Bangalore
Bangalore
KARNATAKA
560100
India |
| Phone |
09845519111 |
| Fax |
9128082820 |
| Email |
Anil.Dr@syngeneintl.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Paushali Mukherjee |
| Designation |
Program Director |
| Affiliation |
Malaria Vaccine Development Program |
| Address |
Malaria Vaccine Development,Room No.1, Program ICGEB Campus Aruna Asaf Ali Marg New Delhi.
New Delhi
DELHI
110067
India |
| Phone |
911126741331 |
| Fax |
911126741384 |
| Email |
paushali.mukherjee@mvdp.org.in |
|
Details of Contact Person
Public Query
|
| Name |
Dr Ramesh KS MD |
| Designation |
Manager Medical and Regulatory Affairs |
| Affiliation |
Syngene International Ltd |
| Address |
Syngene International Ltd
Clinical development, Tower-1, Semicon Park Electronics City, Phase-2, Hosur Road
Bangalore
KARNATAKA
560100
India |
| Phone |
9686679369 |
| Fax |
9128082820 |
| Email |
Ramesh.Ks@syngeneintl.com |
|
|
Source of Monetary or Material Support
|
| Biotechnology Industry Research Assistance Council (BIRAC)
(A Government of India Enterprise)
1st Floor, MTNL Building, 9, CGO Complex,
Lodhi Road, New Delhi-110003 |
|
|
Primary Sponsor
|
| Name |
ICGEB |
| Address |
International Center for Genetic Engineering and Biotechnology (ICGEB) Aruna Asaf Ali Marg New Delhi 110067 India |
| Type of Sponsor |
Research institution |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Multi Vaccines Development Program |
International Center for Genetic Engineering and Biotechnology (ICGEB) Aruna Asaf Ali Marg New Delhi 110067 India |
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Anil K MBBS MD Medicine |
Syngene International Limited |
Syngene International Limited, Clinical Development Department,Human Pharmacology Unit,Tower 1, Ground floor, Semicon Park, Electronics City Phase 2, Hosur Main Road, Bangalore 560100 India
Bangalore
KARNATAKA |
9128082771
9128082820
Anil.Dr@syngeneintl.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Sri Venkateshwara Hospital Ethics Committee, # 27, 29th Main road Rashtra Kuvempu Nagara, BTM 2nd stage, BTM layout Bengaluru-560076 Karnataka, India |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Healthy Human Volunteers |
malaria naive healthy Indian adult males |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Bivalent (JAIVAC-2) P. falciparum vaccine |
Bivalent P. falciparum malaria vaccine in three dose escalating cohorts (Cohort 1, 2 and 3) corresponding to 30, 45, 75 µg single dose. Study duration upto 240 days for the Assessment of the safety and tolerability of above said three different IM doses of malaria vaccine candidate. |
| Comparator Agent |
Hepatitis-B vaccine |
I.M. injection of Hepatitis-B Vaccine, single dose adult vial of 1.0 mL will be used as comparator in this study. Study duration of 240 days |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
45.00 Year(s) |
| Gender |
Male |
| Details |
1. Male subject 18 to 45 years of age at the time of informed consent (both years inclusive).
2. Willing and having the capacity to provide voluntary free informed consent for participation evidenced by signing of the IEC approved informed consent document.
3. Subject is in good general health and is free from clinically significant health problems as determined by medical history, physical examination including vital parameters and clinical laboratory evaluations that include haematology, chemistry, urinalysis and serology.
4. Willing to be available for the duration of the study with no plans to travel outside the study area, reachable by phone.
5. Capable and willing to complete and return diary cards
6. Able to participate during the whole study period and to attend all follow-up visits
7. Willing to undergo HIV test
8. Must agree to use one of the following medically acceptable birth control measures throughout the duration of the study (birth control counselling and measures will be provided by clinical trial site as required) Double barrier method (e.g. condom with spermicidal jelly) OR Subjects must be surgically sterile (undergone vasectomy)
9. Willing to take intramuscular injection |
|
| ExclusionCriteria |
| Details |
1. Any past history of malaria
2. Simultaneous participation in any other intervention clinical trial
3. Subject with evidence of IgG antibodies against PfMSP119, PfMSP311 and PfF2 antigens as measured by ELISA
4. Has prior history of immunisation with Hepatitis B vaccine
5. Previous history of receipt of any other malaria vaccine
6. HbA1c value reported > 6% at Screening visit
7. History of allergic reactions, hypersensitivity or anaphylaxis to immunizations, to any of the components of the study vaccines (including adjuvant or peptide) or of serious allergic reactions that required hospitalisation or emergency medical care
8. Use of an investigational or non-registered drug or vaccine within ninety (90) days prior to enrolment or expects to receive such an agent during the study period.
9. Clinical or laboratory evidence of significant systemic disease, including hepatic, renal, cardiac, immunologic or haematological disease, HIV positive or have any other known immunodeficiency
10. Have a history of autoimmune disease (including inflammatory bowel disease, haemolytic anaemia, autoimmune hepatitis, rheumatoid arthritis, lupus, etc.) or connective tissue disease or have any other serious underlying medical condition. Includes the conditions and diagnoses defined as AESI (Adverse Events of Special Interest)
11. Chronic administration (defined as more than 14 days) of immuno-suppressants or other immune-modifying drugs or cytotoxic therapies (chemotherapy or radiotherapy) within six months prior to the first Immunization. This includes any dose level of oral steroids or inhaled steroids, but not topical steroids.
12. Received a blood transfusion within the past 3 months
13. History of splenectomy
14. Subject has clinically significant laboratory abnormalities, which will include haematology, biochemistry, urinalysis, at the time of screening as determined by the Investigator.
15. Clinical or laboratory presence of Hepatitis B, C or HIV infection or Syphilis
16. Subject with an abnormal 12-lead ECG at screening associated with relevant clinical symptoms/signs suggestive of cardiac pathology
17. Subject with an abnormal Chest X-Ray associated with relevant clinical symptoms/signs of respiratory pathology at screening/ anytime in the past 6 months.
18. Subject gives a history of social, occupational and/ or family problems due to illicit alcohol or drug abuse (to be determined by Urine Drug Screen) within the past 12 months.
19. Has any other condition that, in the opinion of the Principal Investigator, may jeopardise the safety and rights of the volunteer, may interfere with the capacity to provide free and willing informed consent or render the subject unable to comply with the requirements of the study protocol. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Participant Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To evaluate the safety and tolerability profile of three different doses of Bivalent (JAIVAC-2: PfMSPFu24+PfF2/Alhydrogel) malaria vaccine candidate |
Immediate reactogenicity within the first hour after each Immunization,
Solicited AEs occurring from one hour post Immunization till day 7,
unsolicited AEs from one hour post Immunization till Day 28 days,
SAE’s from the signing of ICD till the last follow-up visit. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Assessment of the humoral response of Bivalent malaria vaccine by measuring the IgG antibody response to antigens PfMSP119, PfMSP311 and PfF2 by Enzyme Linked Immunosorbent Assay and Immunofluorescence (IFA) in healthy Indian male subjects, 18 to 45 years of age. |
The level of IgG antibodies developed against PfMSP119, PfMSP311 and PfF2 by ELISA on Visit 1/ Day 0, Visit 9/ Day 56, Visit 13/ Day 84 and Visit 14/Day 180.
To verify the ability of the IgG antibodies developed against PfMSP119, PfMSP311 and PfF2 to recognise the native protein on late stage P. falciparum schizonts and merozoites in vitro by Immunofluorescence Assay (IFA) on Visit 1/ Day 0, Visit 13/Day 84 and Visit 14/ Day 180.
0, Visit 13/ Day 84, Visit 14/Day 180. |
|
|
Target Sample Size
|
Total Sample Size="45"
Sample Size from India="45"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 1 |
|
Date of First Enrollment (India)
|
06/03/2020 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="6" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Other (Terminated) |
|
Publication Details
|
Not yet |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
This is a Phase I, randomized, controlled, dose-escalating,
single-blind clinical trial for assessment of the safety, tolerability
and immunogenicity of Bivalent (JAIVAC-2) P. falciparum malaria vaccine
consisting of two recombinant P. falciparum malaria antigens, PfMSPFu24 and
PfF2 formulated with Alhydrogel adjuvant (PfMSPFu24+PfF2/Alhydrogel) in healthy
malaria naïve Indian male adult subjects aged 18-45 years (both inclusive).The study involves administration
of investigational vaccine PfMSPFu24+PfF2/Alhydrogel in three dose-escalating
cohorts corresponding to three dosages of 30, 45 and 75 µg (of each antigen,
PfF2 and PfMSPFu24) with constant dosage of adjuvant Alhydrogel (850 µg).
The dose escalating design will allow study of safety (Immediate reactogenicity
within the first hour after each Immunization, Solicited AEs occurring from one
hour post Immunization till day 7, unsolicited AEs from one hour post
Immunization till Day 28 days, SAE’s from the signing of ICD till the last
follow-up visit and Laboratory safety during conduct of study) and
immunogenicity of different doses of PfMSPFu24+PfF2/Alhydrogel.
The control vaccine to be used is
Hepatitis B vaccine. In each cohort, 15 subjects will be enrolled.
Following a 4:1 randomization scheme, twelve (12) subjects will receive
Bivalent P. falciparum malaria vaccine while three (03)
subjects will receive Hepatitis-B vaccine. Therefore, in total for this Phase I
study forty-five (45) malaria naïve healthy male adults will be enrolled as
subjects: thirty-six (36) subjects will receive Bivalent P.
falciparum malaria vaccine (12 subjects in each cohort) and nine (09)
subjects will receive Hepatitis B vaccine (03 subjects in each cohort).
Randomization and blinding will control for possible biases during study
conduct. This study shall be completed when all the protocol defined visits and
assessments are completed for all the three Study cohorts. An independent
Data Safety Monitoring Board (DSMB) will maintain a safety oversight for the
study and will advise on dose escalation of Bivalent P.
falciparum malaria vaccine to the next higher dose cohort after
reviewing the 7day safety data post first immunization for all 15 subjects of
the previous cohort. Thus, enrolment for each new cohort shall have a delay of
at least about 21 days from previous cohort so as to allow for safety data to
be available & assessed by DSMB.
The volunteers will be enrolled at a single trial site (Human Pharmacology unit
of Syngene International Limited, Bengaluru, India). Study population will
include healthy Indian male subjects between 18 to 45 years of age (both
inclusive). The subjects will be recruited from the healthy volunteer database
of the study site. The recruitment in the study cohorts will begin sequentially
but the study periods after initiation may overlap. Within each cohort, the
study duration shall be divided into three periods: Screening period (21 days),
Immunization period (56 days) and Follow-up period (up to day 240). |