A Phase 1b, Randomised, Controlled Age De-escalation, Dose-finding Study to Evaluate the Safety, Reactogenicity and Immunogenicity of Full-length MSP1/GLA-SE (SUM-101) Malaria Vaccine in Healthy Young Children, and Infants in Burkina Faso.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 2
- 主要终点
- Local and systemic solicited adverse events (AEs) at least possibly related to the SUM-101.
研究概览
简要总结
This clinical trial aims to learn about the safety and immunogenicity of the blood-stage malaria vaccine candidate SUM-101 in infants and children, paving the way for its incorporation into a multi-stage malaria vaccine. This will be the first time SUM-101 will be evaluated for safety and immunogenicity in infants and children. The main questions it aims to answer are:
- Are the 3 doses of full-length MSP1/GLA-SE (SUM-101) in young children and infants safe?
- Do the 3 doses of full-length MSP1/GLA-SE (SUM-101) in young children and infants produce any reactogenicity?
- How is the immunogenicity in young children and infants generated by the 3 doses of full-length MSP1/GLA-SE (SUM-101)?
- What is the optimal dose of the full-length MSP1/GLA-SE (SUM-101) in young children and infants? The study will be divided into two arms with 5 groups conducted at a single centre. In total, 39 healthy malaria-pre-exposed infants and children aged 5 months to 5 years will be enrolled in this study.
Participants will be included in one of the following groups:
- Arm 1_Group 1 (open-label design): This will be the first cohort enrolled to assess safety in children (18 months - 5 years) before the vaccination of infants commences. Therefore, all participants in Arm 1 will receive one dose of SUM-101 vaccine (25µg MSP1 + 2µg GLA-SE) on D0, D28 and D56.
- Arm 2_Group 2-3 (randomised, controlled, double-blind design): This will be the second cohort enrolled to assess safety in the target population (infants aged 5-17 months). Infants will be assigned to Groups 2-3 to enable evaluation of one dose of MSP1 (10µg) and two doses of GLA-SE (2µg and 1µg). The infants in each group will be randomised into A) a vaccine arm (12 participants) and B) a control arm (3 participants). All participants in Groups 2-3 will receive one doses of SUM-101 vaccine or Verorab® (Rabies vaccine) on D0, D28 and D56.
Participants will visit the clinic for screening and once selected for enrolment. No later than 28 days after selection participants will receive the 1st vaccination (Visit Day 0) and 2nd and 3rd Vaccination on Day 28 and Day 56. On Day 1 to 6 days post each vaccination (Day 1-6, Day 29-34 and Day 57-62) each participant will be visited at home daily by a field worker for assessment and recording of any solicited and unsolicited AEs (Reactogenicity visits).
详细描述
Experimental design: Phase Ib, age de-escalation and dose-escalation study. A total of 39 participants will be enrolled, consisting of healthy children (18 months-5 years) and infants (5-17 months) residing in Sabou health district or in Banfora health district, Burkina Faso. The participants will be divided into three groups. Two doses of MSP1 (25μg and 10μg) and two doses of GLA-SE (2μg and 1μg) will be evaluated.
Group 1 will be the first cohort enrolled to assess safety in children before the vaccination of infants commences. There will be no control arm, therefore, all participants in Group 1 will receive three doses of SUM-101 vaccine on D0, D28 and D56 in an open-label design.
Groups 2 and 3 will consist of the target population (infants aged 5-17 months) who will be randomised into A) a vaccine arm (12 participants) and B) a control arm (3 participants). Vaccination of Groups 2 and 3 will be conducted in a double-blinded manner. All participants in Groups 2 and 3 will receive three doses of either SUM-101 vaccine or Verorab® (rabies vaccine) on D0, D28 and D56.
Because this is the first time SUM-101 is administered to children and infants, the vaccinations will be staggered with regular safety reviews. A dose of 25μg MSP1+2μg GLA-SE will be used in children in Group 1. This choice is based on the good safety and tolerability data obtained in malaria naïve adults in Germany using this dose. Subject to favourable safety data from children, a lower dose of 10μg MSP1 with 1μg or 2μg of GLA-SE will be used in infants in Groups 2A and 3A. As an additional safety measure, the first 3 participants enrolled in Group 1 will be sentinels who will be vaccinated in an open-label manner. To ensure blinding, the first 4 participants enrolled in Groups 2 and 3 will be sentinels who will be vaccinated with either SUM-101 or control vaccine. The sentinel participants will be vaccinated one at a time (not at the same time) at least 72 hours before the remaining participants are vaccinated.
For the children cohort, the trial will be an open-label uncontrolled trial (with no control group), as the cohort of children will be used as a transition group between adults and infants. Tolerance and safety in adults have already been demonstrated in previous trials in Germany and Tanzania. The safety of the lowest dose used in adults will be evaluated in children in an open-label manner (without a control group, in a staggered fashion with a sentinel approach and a review of the data by the Data Safety Monitoring Board -DSMB-) to ensure a safe transition to the target group of the study, the infant population, where the vaccine will also be administered in a staggered fashion with a sentinel approach. Adjuvant doses are informed by safety and immunogenicity data from previous SUM-101 clinical trials and as recommended by the adjuvant manufacturer and another clinical trial (NCT04607408).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This trial will be conducted in a double-blinded manner. Namely, the participants, site staff, sponsor staff, the study monitor(s) and the trial statistician will be blinded to the treatment allocation. The independent statistician and the pharmacist are not blind throughout the study.
入排标准
- 年龄范围
- 5 Months 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Resident in the study area villages and participant's parent(s)/legal guardian anticipate being available for vaccination and follow-up for following last dose of vaccination.
- •Z-score of weight-for-age within ±2SD.
排除标准
- •Clinically significant skin disorder (psoriasis, contact dermatitis etc.), immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, neurological illness, major congenital defects, malnutrition requiring hospital admission and anaemia.
- •History of allergic reaction, significant IgE-mediated event, or anaphylaxis to immunisation.
- •Clinically significant laboratory abnormality as judged by the study investigator.
- •History of blood transfusion.
- •Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
- •Previous vaccination with experimental malaria vaccines.
- •Participation in another research study/clinical trial involving receipt of an investigational medicinal product or planned use during the study period.
- •Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection (no HIV testing); asplenia; recurrent, severe infections and chronic immunosuppressant medication (For corticosteroids, this will mean prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed).
- •Any significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant´s ability to participate in the trial.
研究组 & 干预措施
Infants (5-17 months)
For safety reasons, vaccination of infants will be staggered based on the dosage of MSP1 and the GLA-SE adjuvant used. The following dosages will be evaluated:
- Group 2: 10µg MSP1 + 2.5µg GLA-SE
- Group 3: 10µg MSP1 + 5µg GLA-SE
- Group 4: 25µg MSP1 + 2.5µg GLA-SE
- Group 5: 25µg MSP1 + 5µg GLA-SE Enrollment and vaccination of infants will start with Groups 2 and 3, and only proceed to Groups 4 and 5 if there are no safety concerns. The first infants enrolled into each group will be sentinels (4 per group). The At least tThree out four sentinels will receive the SUM-101 vaccine dose assigned to their respective groups. The participants enrolled into Groups 2-5 (both sentinels and followers) will be randomised at a ratio of 4:1 into vaccine and control arms. In total, 12 participants per group will receive the SUM-101 vaccine (either 25µg or 10µg of MSP1 and either 5µg or 2.5µg of GLA-SE) and 3 participants will receive the control vaccine (rabies vaccine, Verorab®).
干预措施: SUM-101 (Biological)
Children (18 months - 5 years)
Children (18 months - 5 years) will not be randomised. The first 3 participants will be enrolled as sentinel participants prior to the 6 follower participants. The nine participants of Group 1 will receive three administrations of the SUM-101 vaccine (25µg MSP1 + 5µg GLA-SE) in an open-label design.
干预措施: SUM-101 (Biological)
结局指标
主要结局
Local and systemic solicited adverse events (AEs) at least possibly related to the SUM-101.
时间窗: After each vaccination (done on Day0, Day28 and Day56) up to 7 days after.
Local and systemic solicited adverse events (AEs) at least possibly related to the investigational medicinal product (IMP) SUM-101 will be recorded to evaluate safety and reactogenicity.
Local and systemic unsolicited reactogenicity adverse events (AEs).
时间窗: Recorder after each vaccination (done on Day0, Day28 and Day56) up to 28 days later.
Local and systemic unsolicited reactogenicity will be recorded to evaluate the safety and reactogenicity of SUM-101.
Number of participants with treatment-related adverse events as assessed by safety laboratory measures of haematology and biochemistry.
时间窗: Between baseline (Day 0 before 1st vaccination) to 28 days after each vaccination.
Changes in laboratory safety parameters as summarised as absolute values of: Haematology (RBC count, WBC count with differentials (neutrophil, lymphocyte and eosinophil), Haemoglobin (Hgb), Haematocrit and platelet count. Biochemistry-, Serum creatinine, Alanine aminotransferase (ALT), Aspartate Aminotransferase (AST) and Total bilirubin.
Any serious adverse events (SAE) occurring during the whole study duration.
时间窗: Recorded after signature of informed consent until the participant's last visit (Day 140)
Any serious adverse events (SAE) occurring after signature of the informed consent until the participant's last visit to evaluate the safety and reactogenicity of SUM-101.
次要结局
- IgG antibody titres against full-length MSP1(Changes assessed between Day 0 (pre-vaccination) up to Day 140 (last follow up visit).)
- Identification of the dose of full-length MSP1/GLA-SE (SUM-101) in young children and infants that give the safety profile.(Recorded from after 1st vaccination (Day 0 post-vaccination) until the participant's last visit (Day 140))
- Identification of the dose of full-length MSP1/GLA-SE (SUM-101) in young children and infants that give the strongest immune response.(Recorded from after 1st vaccination (Day 0 post-vaccination) until the participant's last visit (Day 140))