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
试验速览
- 阶段
- 1 期
- 状态
- Other
- 发起方
- ICGEB
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- To evaluate the safety and tolerability profile of three different doses of Bivalent (JAIVAC-2: PfMSPFu24+PfF2/Alhydrogel) malaria vaccine candidate
研究概览
简要总结
This is a Phase I, randomized, controlled, dose-escalating,single-blind clinical trial for assessment of the safety, tolerabilityand immunogenicity of Bivalent (JAIVAC-2) P. falciparum malaria vaccineconsisting of two recombinant P. falciparum malaria antigens, PfMSPFu24 andPfF2 formulated with Alhydrogel adjuvant (PfMSPFu24+PfF2/Alhydrogel) in healthymalaria naïve Indian male adult subjects aged 18-45 years (both inclusive).The study involves administrationof investigational vaccine PfMSPFu24+PfF2/Alhydrogel in three dose-escalatingcohorts 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 reactogenicitywithin the first hour after each Immunization, Solicited AEs occurring from onehour post Immunization till day 7, unsolicited AEs from one hour postImmunization till Day 28 days, SAE’s from the signing of ICD till the lastfollow-up visit and Laboratory safety during conduct of study) andimmunogenicity of different doses of PfMSPFu24+PfF2/Alhydrogel.
The control vaccine to be used isHepatitis B vaccine. In each cohort, 15 subjects will be enrolled.Following a 4:1 randomization scheme, twelve (12) subjects will receiveBivalent P. falciparummalaria vaccine while three (03)subjects will receive Hepatitis-B vaccine. Therefore, in total for this Phase Istudy forty-five (45) malaria naïve healthy male adults will be enrolled assubjects: thirty-six (36) subjects will receive Bivalent P.falciparummalaria 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 studyconduct. This study shall be completed when all the protocol defined visits andassessments are completed for all the three Study cohorts. An independentData Safety Monitoring Board (DSMB) will maintain a safety oversight for thestudy and will advise on dose escalation of Bivalent P.falciparummalaria vaccine to the next higher dose cohort afterreviewing the 7day safety data post first immunization for all 15 subjects ofthe previous cohort. Thus, enrolment for each new cohort shall have a delay ofat least about 21 days from previous cohort so as to allow for safety data tobe available & assessed by DSMB.
The volunteers will be enrolled at a single trial site (Human Pharmacology unitof Syngene International Limited, Bengaluru, India). Study population willinclude healthy Indian male subjects between 18 to 45 years of age (bothinclusive). The subjects will be recruited from the healthy volunteer databaseof the study site. The recruitment in the study cohorts will begin sequentiallybut the study periods after initiation may overlap. Within each cohort, thestudy duration shall be divided into three periods: Screening period (21 days),Immunization period (56 days) and Follow-up period (up to day 240).
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 45.00 Year(s)（—）
- 性别
- Male
入选标准
- •Male subject 18 to 45 years of age at the time of informed consent (both years inclusive).
- •Willing and having the capacity to provide voluntary free informed consent for participation evidenced by signing of the IEC approved informed consent document.
- •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.
- •Willing to be available for the duration of the study with no plans to travel outside the study area, reachable by phone.
- •Capable and willing to complete and return diary cards
- •Able to participate during the whole study period and to attend all follow-up visits
- •Willing to undergo HIV test
- •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)
- •Willing to take intramuscular injection.
排除标准
- •Any past history of malaria
- •Simultaneous participation in any other intervention clinical trial
- •Subject with evidence of IgG antibodies against PfMSP119, PfMSP311 and PfF2 antigens as measured by ELISA
- •Has prior history of immunisation with Hepatitis B vaccine
- •Previous history of receipt of any other malaria vaccine
- •HbA1c value reported > 6% at Screening visit
- •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
- •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.
- •Clinical or laboratory evidence of significant systemic disease, including hepatic, renal, cardiac, immunologic or haematological disease, HIV positive or have any other known immunodeficiency
- •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)
- •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.
- •Received a blood transfusion within the past 3 months
- •History of splenectomy
- •Subject has clinically significant laboratory abnormalities, which will include haematology, biochemistry, urinalysis, at the time of screening as determined by the Investigator.
- •Clinical or laboratory presence of Hepatitis B, C or HIV infection or Syphilis
- •Subject with an abnormal 12-lead ECG at screening associated with relevant clinical symptoms/signs suggestive of cardiac pathology
- •Subject with an abnormal Chest X-Ray associated with relevant clinical symptoms/signs of respiratory pathology at screening/ anytime in the past 6 months.
- •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.
- •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.
结局指标
主要结局
To evaluate the safety and tolerability profile of three different doses of Bivalent (JAIVAC-2: PfMSPFu24+PfF2/Alhydrogel) malaria vaccine candidate
时间窗: 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.
次要结局
- 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.)