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Trial registered on ANZCTR


Registration number
ACTRN12619001022156
Ethics application status
Approved
Date submitted
21/06/2019
Date registered
16/07/2019
Date last updated
16/07/2019
Date data sharing statement initially provided
16/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and immunogenicity of ACT-1239 in healthy volunteers
Scientific title
A Phase I Study of the Safety and Immunogenicity of ACT-1239, a Vaccine for Plasmodium falciparum Malaria
Secondary ID [1] 298465 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malaria 313227 0
Condition category
Condition code
Infection 311674 311674 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 314716 0
Prevention
Intervention code [2] 314940 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 320382 0
To evaluate the safety of escalating doses of ACT-1239 administered intramuscularly (IM) to healthy malaria naïve participants according to a repeat vaccination schedule (at Day 1, Day 29 and Day 57)
Timepoint [1] 320382 0
Assessment of AEs/SAEs, recording concomitant medications, physical exams, obtaining vitals and collection of blood and urine samples. On-site assessments to occur on Days 1, 3, 15, 29, 31, 43, 57, 59, 71, 85 and 6 months and 12 months after final vaccination. With telephone calls on Days 2, 8, 30, 36, 58 and 64 to asses AEs/SAEs and concomitant medications.
Primary outcome [2] 320644 0
Immunogenicity outcome is assessed using the following assays:
ELISA and ELISPOT assays. With on-site samples drawn on Days 1, 15, 29, 43, 57, 71 and 6 months and 12 months after final vaccination.
Timepoint [2] 320644 0
Immunogenicity outcome is assessed using the following assays:
ELISA and ELISPOT assays. With on-site samples drawn on Days 1, 15, 29, 43, 57, 71 and 6 months and 12 months after final vaccination.
Secondary outcome [1] 371407 0
To determine the humoral response to the T1B peptide, in terms of peptide-specific antibody titers (as measured by ELISA) and functionality (hepatocyte invasion assay [HIA]) in whole blood. This is a composite secondary outcome and correctly captured as one outcome.
Timepoint [1] 371407 0
Day 1, Day 15, Day 29, Day 43, Day 57, Day 71, Month 6 and Month 12
Secondary outcome [2] 371408 0
Exploratory analysis of biomarkers of cellular responses to vaccination, as measured by enzyme linked immunospot (ELISPOT) of whole blood samples.
Timepoint [2] 371408 0
Day 1, Day 15, Day 29, Day 43, Day 57, Day 71, Month 6 and Month 12

Eligibility
Key inclusion criteria
• 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
Minimum age
18 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• 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

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 13972 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 26747 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 303008 0
Commercial sector/Industry
Name [1] 303008 0
Artificial Cell Technologies, Inc.
Address [1] 303008 0
5 Science Park, Suite 13,
New Haven, CT, 06511
Country [1] 303008 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Artificial Cell Technologies, Inc.
Address
5 Science Park, Suite 13,
New Haven, CT, 06511
Country
United States of America
Secondary sponsor category [1] 302980 0
Commercial sector/Industry
Name [1] 302980 0
Clinical Network Services (CNS) Pty Ltd
Address [1] 302980 0
Level 2, 381 MacArthur Ave,
Hamilton, QLD, 4007
Country [1] 302980 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303559 0
Alfred Health - Alfred Hospital Human Research Ethics Committee
Ethics committee address [1] 303559 0
Office of Ethics and Research Governance,
Level 5, 553 St Kilda Road,
Melbourne, VIC, 3004
Ethics committee country [1] 303559 0
Australia
Date submitted for ethics approval [1] 303559 0
05/06/2019
Approval date [1] 303559 0
28/06/2019
Ethics approval number [1] 303559 0
317/19

Summary
Brief 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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94082 0
Dr Jason Lickliter
Address 94082 0
Centre For Clinical Studies (AMREP)
Level 5, Burnet Institute
89 Commercial Road
Melbourne, VIC, 3004
Country 94082 0
Australia
Phone 94082 0
+61 3 9089 8214
Fax 94082 0
Email 94082 0
J.Lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 94083 0
Dr Jason Lickliter
Address 94083 0
Centre For Clinical Studies (AMREP)
Level 5, Burnet Institute
89 Commercial Road
Melbourne, VIC, 3004
Country 94083 0
Australia
Phone 94083 0
+61 3 9089 8214
Fax 94083 0
Email 94083 0
J.Lickliter@nucleusnetwork.com.au
Contact person for scientific queries
Name 94084 0
Dr Jeff Powell
Address 94084 0
Artificial Cell Technologies, Inc.
5 Science Park, Suite 13
New Haven, CT 06511
Country 94084 0
United States of America
Phone 94084 0
+1 203 980 3174
Fax 94084 0
Email 94084 0
jpowell@artificialcelltech.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual patient data will not be made available for this study. All subject data obtained will be de-identified and captured in a final study report that will not identify individual participants.
What supporting documents are/will be available?
No other documents available
Summary results
No Results