Safety and immunogenicity of ACT-1239 in healthy volunteers
A Phase I Study of the Safety and Immunogenicity of ACT-1239, a Vaccine for Plasmodium falciparum Malaria
Artificial Cell Technologies, Inc.
50 participants
Aug 16, 2019
Interventional
Conditions
Summary
The primary aims of this first-in-human study are to investigate the safety and immunogenicity of ACT-1239, a Vaccine for Plasmodium falciparum Malaria. Up to 50 participants will be recruited to five Cohorts of 10 participants each in this open-label, dose escalation, first in human (FIH) study. Participants will receive an intramuscular (IM) injection of ACT-1239 at the specified dose level per their allocated treatment group. Two sentinel participants of each Cohort will be dosed initially. If dosing of these sentinel participants proceeds without clinically-significant adverse events (AEs) over a 24 hour period, the remaining 8 participants of that Cohort will be dosed. Participants will receive a total of 3 IM vaccinations, administered 28 days apart. The dose level will be established following assessment of safety data of the preceding cohorts but is planned to increase from 1µg (Cohort 1) to 3µg (Cohort 2), 10µg (Cohort 3), 30µg (Cohort 4) and 100µg (Cohort 5). Participants will be followed up post-vaccinations via phone call and clinic visits up until Day 85 following vaccination number 3 ( the last administered vaccination) for safety and other assessments. Participants will then be required to return to the site at 6 and 12 months for safety follow up.
Eligibility
Inclusion Criteria7
- Healthy males and females aged between 18-45 years (inclusive)
- Body mass index (BMI) 18-32 kg/m2 (inclusive);
- Negative test for selected drugs of abuse at screening (does not include alcohol) and prior to enrollment on Day 1;
- Non-pregnant and non-lactating females, and either surgically sterile for a minimum of 6 months, or use highly effective contraceptive method (oral contraceptives pills, long-acting implantable hormones, injectable hormones, a vaginal ring or an intrauterine device [IUD]) from screening until at least 3 months after the last vaccination with ACT-1239, or be post-menopausal for greater then or equal to 12 months. Post-menopausal status will be confirmed through testing of follicle-stimulating hormone (FSH) levels (greater than or equal to 40 IU/mL) at screening for amenorrhoeic female participants. Females who are abstinent from heterosexual intercourse will also be eligible;
- Women of child-bearing potential (WOCBP) must have a negative pregnancy test at screening and on Day 1 prior to enrollment and be willing to have additional pregnancy tests as required throughout the study;
- Surgically sterile males, or if engaged in sexual relations with a WOCBP, the participant and his partner must be surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or using an acceptable, highly effective contraceptive method from screening for at least 3 months after the last vaccination with ACT-1239. Acceptable methods of contraception include the use of condoms and the use of an effective contraceptive for the female partner (WOCBP) that includes: OCPs, long acting implantable hormones, injectable hormones, a vaginal ring or an IUD. Male participants whose female partner is post-menopausal, and participants who are abstinent from heterosexual intercourse will also be eligible. Male participants must agree to refrain from donating sperm from screening for at least 3 months after the last vaccination with ACT-1239;
- No plans to travel to a malaria endemic area over the study duration
Exclusion Criteria23
- Pregnant or lactating females at screening or plans to become pregnant or breastfeed from the time of enrollment until 3 months after the last vaccination;
- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, rheumatologic, psychiatric, or neurologic disorders (including seizure disorder and chronic migraine headaches);
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past five years, regardless of whether there is evidence of local recurrence or metastases;
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational vaccine administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the participant inappropriate for entry into this study;
- History of severe allergy (requiring hospital care), severe reaction to any drug or prior vaccination, or any known or suspected allergies or sensitivities to any component of the investigational vaccine;
- Immunosuppression caused by disease;
- History of autoimmune disorder;
- Seropositive for HIV or Hepatitis C Virus or Hepatitis B surface antigen (HBsAg) positive;
- History of splenectomy or of condition affecting splenic function;
- Significant infection or other acute illness, including fever over 37.5°C on the day of enrollment;
- Birthmarks, tattoos, wound or other skin conditions over the deltoid region of both arms that, in the Investigator’s opinion, could reasonably obscure and interfere with evaluation of local injection site reactions;
- Thrombocytopenia or bleeding disorder contraindicating IM vaccination;
- Inadequate venous access to allow collection of blood samples;
- Receipt of immunoglobulins or blood products within 3 months of first vaccination or any planned administration during the study period;
- Use of immunosuppressive or other immune-modifying drugs within six months of vaccination and for the study duration (inhaled and topical steroids are permitted);
- Use of prescription or non-prescription drugs, and herbal supplements within 14 days or 5 half-lives (whichever is the longer) prior to the first vaccination. As an exception, ibuprofen (preferred) may be used at doses of up to 800 mg/day, or paracetamol at doses up to 4 g/day may be used for minor ailments during the course of the study, at the Investigator’s discretion, without prior consultation with the Sponsor’s MM. Paracetamol and ibuprofen may be used for treatment of AEs occurring after vaccination, but should not be administered prophylactically for such events, as such use may mask reactogenicity and interfere with immune responses. Limited use of other non-prescription medications or vitamins not believed to affect participant safety, or the overall results of the study may be permitted on a case-by-case basis following approval by the Sponsor in consultation with the Investigator;
- Receipt of any licensed vaccine within 30 days prior to first vaccination or before the 6 month follow up visit (6 months following last administered vaccination);
- Use of any investigational or non-registered drug or vaccine within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study vaccine or planned use during the study period;
- Any history of malaria; including prior participation in a malaria challenge study, prior participation in a malaria vaccine trial or has travelled to or lived (for more than 2 weeks) in a malaria-endemic region during the past 12 months;
- History of alcohol or drug abuse or psychiatric disorder;
- Participant unwilling to abstain from blood donation during the course of the study, and/or participation in any research study involving blood sampling, or blood donation during the 2 months prior to the screening visit;
- Participant unwilling or unable to comply with the restrictions described in this protocol;
- Any participant who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development
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Interventions
This study will enrol up to 50 subjects sequentially allocated to up to 5 treatment groups (10 subjects per group). Subjects will be assigned to the study drug (ACT-1239) and will receive a single intramuscular injection in the deltoid muscle of the arm on Day 1, Day 29 and Day 57 of their study participation. It is anticipated that subjects enrolled to Group 1 will receive ACT 1239 at a dose of 1 µg for each intramuscular injection, subjects enrolled to Group 2 will receive ACT 1239 at a dose of 3 µg for each intramuscular injection, subjects enrolled to Group 3 will receive ACT 1239 at a dose of 10 µg for each intramuscular injection, subjects enrolled to Group 4 will receive ACT 1239 at a dose of 30 µg for each intramuscular injection and subjects enrolled to Group 1 will receive ACT 1239 at a dose of 100 µg for each intramuscular injection. Sentinel dosing will be used for each of the cohorts whereby, tThe first 2 subjects in each cohort will be sentinels. For the first vaccination on Day 1, sentinel subjects will be vaccinated approximately 24 hours before the remaining subjects in theat treatment groupcohort. In the absence of any clinically significant safety signals in these sentinel subjects over this period, the remaining subjects in the cohort will proceed to be be enrolled and vaccinated, with at a minimum safety observation period interval between subjects of 60 minutes apart to allow for the monitoring of any acute events. Subjects will be discharged Discharge from the site will occur on Day 1the same day, in the absence of clinically significant safety signals and following completion of all assessments. A phone call between site staff and the subjects will occur on Day 2 and Day 8 post-vaccination for safety monitoring. Subjects will return to the site attend scheduled onsite visits on Day 3 and Day 15 for safety and other assessments. The studies Safety Monitoring Committee (SMC) will convene 7-days after the first vaccination and if there are no safety concerns identified the subjects will return to the site to receive a second vaccination via intramuscular injection into the deltoid muscle on Day 29 and again return to the site to receive the third vaccination via intramuscular injection into the deltoid muscle on Day 57. A phone call between site staff and subjects will occur two days and eight days (Day 30 and Day 36) following the second vaccination and two days and eight days ( Day 58 and Day 64) following the third vaccination for safety monitoring. Subjects will attend scheduled onsite visits on Day 31, Day 43, Day 59, Day 71 and Day 85 and return to the site for safety follow up visits 6 months and 12 months after receiving the third vaccination.
Locations(1)
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ACTRN12619001022156