A Phase 1 interventional study of PAMVAC and Alhydrogel in Malaria, Antepartum, sponsored by University Hospital Tuebingen. Completed at 1 site in Benin. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-06-26.
Sponsored by University Hospital Tuebingen · Phase 1, Interventional, and Prevention
Despite having developed robust acquired immunity against complications of malaria, women can return to a susceptible state during their first pregnancies and contribute significantly to the burden of severe malaria in highly endemic areas. Naturally acquired protection against placental malaria correlates with the presence of high concentration of immunoglobulin G molecules (IgGs) against VAR2CSA, a parasite protein of the var gene family that is essential for the binding of infected erythrocytes to CSA in the placenta.
To induce high concentrations of specific IgGs, subjects will receive escalating doses of PAMVAC vaccine antigen adjuvanted with Alhydrogel, Glucopyranosyl Lipid Adjuvant-Stable Emulsion (GLA-SE) or Glucopyranosyl Lipid Adjuvant-Liposome-QS-21 Formulation (GLA-LSQ). Three injections with the same dosage and adjuvant will be done, each 28 days apart (Day 0, 28 and 56). Control subjects will receive physiological saline instead of the vaccine and dose escalation will be staggered to ensure safety during the trial.
Phase 1, staggered, two-center, dose-escalation trial. The trial will be conducted in two stages. The first in Germany (first in man and dose escalation) and the second in a malaria-endemic area in the target group (randomized, controlled, dose-finding).
First in man administration and dose escalation from 20 to 50 μg per injection of PAMVAC adjuvanted with Alhydrogel, GLA-SE and GLA-LSQ will be done in healthy, malaria-naïve adults in Germany (Stage 1).
Subsequently, PAMVAC will be administered to healthy, lifelong malaria-exposed nulligravid women in Benin at doses of 50 and 100 μg, adjuvanted with Alhydrogel and GLA-SE (Stage 2).
The PAMVAC vaccine is a VAR2CSA protein-based vaccine, aiming to protect fetus and mother against the adverse effects of placental malaria during pregnancy. As the interaction between the parasite protein VAR2CSA and CSA in the human placenta is a key element in the pathogenesis of placental malaria, a vaccine should elicit the type of immunoglobulins that block the binding of VAR2CSA to CSA. A small sub-unit of the VAR2CSA protein (ID1-ID2a) has been selected as the PAMVAC vaccine antigen. In animal models IgGs induced by immunization with the recombinant PAMVAC antigen are able to inhibit homologous parasite-infected erythrocyte adhesion to CSA in vitro.
The three adjuvants are Alhydrogel, an aluminum hydroxide gel widely used as adjuvant in this trial; GLA-SE and GLA-LSQ, synthetic TLR-4 agonists with a strong immune stimulatory effect formulated either in a stable oil-in-water emulsion (SE) or together with QS-21 (Saponin derived from the Quillaja saponaria tree) as liposome (LSQ).
In Benin, one group will receive a placebo control (physiological saline). Allocation to placebo, PAMVAC+Alhydrogel or PAMVAC+GLA-SE, will be randomized and the trial team as well as the participants will be kept blinded (double-blinded) to their allocation.
All participants (Stage 1+2) will receive three intramuscular injections in four-week intervals.
Each dose-escalation is conditional on a positive safety assessment by an independent Safety Monitoring Board (SMB) and sponsor approval. One individual of each PAMVAC-adjuvant combination will serve as sentinel. The sentinel will be injected one day before the rest of the group.
There will be a minimum of 4 weeks stagger between the first immunization of Groups 1A-3A and Groups 4A-6A.
Group 1A (n = 3) - 20 µg PAMVAC+Alhydrogel Group 2A (n = 3) - 20 µg PAMVAC+GLA-SE Group 3A (n = 3) - 20 µg PAMVAC+GLA-LSQ Group 4A (n = 9) - 50 µg PAMVAC+Alhydrogel Group 5A (n = 9) - 50 µg PAMVAC+GLA-SE Group 6A (n = 9) - 50 µg PAMVAC+GLA-LSQ
Following safety assessment by the SMB after the first dose in Groups 4A-6A and approval by the sponsor, Stage 2 (in Benin) will be initiated. Here, the target population of PAMVAC (healthy nulligravid women in a malaria-endemic area) will be vaccinated. Upon SMB review and approval by the sponsor Groups 1B-2B and half the subjects from the control Group 5B will receive vaccinations. One participant allocated to group 1B, 2B and 5B will receive the first immunization at least one day before the rest of the group.
Group 1B (n=9) - 50 µg PAMVAC+Alhydrogel Group 2B (n=9) - 50 µg PAMVAC+GLA-SE Group 3B (n=3) - 100 µg PAMVAC+Alhydrogel Group 4B (n=3) - 100 µg PAMVAC+GLA-SE Group 5B (n=6) - Placebo (physiological saline solution)
There will be a 4 weeks stagger between Groups 1B-2B and Group 3B-4B and the remaining subjects of the control Group 5B to allow for safety evaluation by the SMB. Here, the same system of sentinel vaccination as for the lower dose will be used; one participant allocated to group 3B, 4B and 5B will receive the first immunization at least one day before the rest of the group.
1,184 studies on the registry are indexed under Malaria; 79 are open to participants now.
This study's enrollment of 66 is below the median of 252 across 937 interventional studies indexed under Malaria.
Browse Malaria studies →University Hospital Tuebingen is the lead sponsor of 490 studies on the registry; 108 are open to participants now.
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You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
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Read whether the line is about a condition or about medicines, and which medicines and doses it means.
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Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The study participant will get 20 µg of PAMVAC adjuvanted with Alhydrogel administrated three times with each time 28 days interval (day 0-28-56)
Biological: PAMVAC · Biological: Alhydrogel
The study participant will get 20 µg of PAMVAC adjuvanted with GLA-SE administrated three times with each time 28 days interval (day 0-28-56)
Biological: PAMVAC · Biological: GLA-SE
The study participant will get 20 µg of PAMVAC adjuvanted with GLA-LSQ administrated three times with each time 28 days interval (day 0-28-56)
Biological: PAMVAC · Biological: GLA-LSQ
The study participant will get 50 µg of PAMVAC adjuvanted with Alhydrogel administrated three times with each time 28 days interval (day 0-28-56)
Biological: PAMVAC · Biological: Alhydrogel
The study participant will get 50 µg of PAMVAC adjuvanted with GLA-SE administrated three times with each time 28 days interval (day 0-28-56)
Biological: PAMVAC · Biological: GLA-SE
The study participant will get 50 µg of PAMVAC adjuvanted with GLA-LSQ administrated three times with each time 28 days interval (day 0-28-56)
Biological: PAMVAC · Biological: GLA-LSQ
The study participant will get 50 µg of PAMVAC adjuvanted with Alhydrogel administrated three times with each time 28 days interval (day 0-28-56)
Biological: PAMVAC · Biological: Alhydrogel
The study participant will get 50 µg of PAMVAC adjuvanted with GLA-SE administrated three times with each time 28 days interval (day 0-28-56)
Biological: PAMVAC · Biological: GLA-SE
The study participant will get 100 µg of PAMVAC adjuvanted with Alhydrogel administrated three times with each time 28 days interval (day 0-28-56)
Biological: PAMVAC · Biological: Alhydrogel
The study participant will get 100 µg of PAMVAC adjuvanted with GLA-SE administrated three times with each time 28 days interval (day 0-28-56)
Biological: PAMVAC · Biological: GLA-SE
The study participant will get Placebo (physiological saline solution) administrated three times with each time 28 days interval (day 0-28-56)
Other: Placebo
Number and grade of adverse events (Grade 1-3 and serious adverse events) possibly, likely and definitely related to vaccination
Time frame: From the first administration of the interventions through study completion, an average of 1 and a half years
Area under the curve of anti-PAMVAC IgG concentration
Time frame: Before first administration, 1, 4, 5, 8, 9, 12, 24 and 36 weeks after first administration
The record gives a start of May 2016, a primary completion of Nov 2017 and a completion of Nov 2017. It does not say whether these dates are actual or estimated.
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This study is completed, as verified in Oct 2016. You cannot join it, but the record below documents what was studied.
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