CTP-MCVF-006

1. Background
Registration Number	INA-9PQMGFP
Date of registry approval	21-11-2023
Registration Date	14-11-2023
Secondary identifiers	Yes
Name of issuing authority (for example protocol number, other registries, etc)	CTP-MCVF-006
Secondary identifier number	CTP-MCVF-006
Scientific study title	A multicenter, randomized, double-blinded, positive-controlled phase Ⅲ clinical trial to evaluate lot-to-lot consistency, immunogenicity and safety of Group ACYW135 Meningococcal Conjugate Vaccine (CRM197) in adults aged 18 to 55 years
Public (popular study title)	CTP-MCVF-006
2. Sponsor and Funding
Primary Sponsor	CanSino Biologics Inc.
Source(s) of monetary or material support	CanSino Biologics Inc.
Name of secondary sponsor	PT Etana Biotechnologies Indonesia
Other partners	Rumah Sakit Husada Utama dan Rumah Sakit Universitas Airlangga sebagai lokasi penelitian, serta PT. Tigermed Consulting Indonesia sebagai CRO.
3. Contact details
Principal Investigator
Principal investigator	Prof. Dr. dr. Erni Juwita Nelwan, PhD, SpPD, K-PTI, dr. Isti Suharijanti, Sp.S(K) , dan Prof. Dr. dr. Nasronudin, Sp.PD-KPTI, FINASIM
City	Surabaya
Country	Indonesia
Principal investigator's affiliation	Rumah Sakit Husada Utama dan Rumah Sakit Universitas Airlangga
Principal Investigator's email address	erni.juwita@ui.ac.id, e.nelwan@gmail.com, dan nasronudindr@yahoo.com
Public Queries
Contact person name for public queries	Name: Dr. Ruijie Wang
Address for public queries	CanSino Biologics Inc.
City	Address: 185, South Avenue, TEDA West District, Tianjin, China
Country	China
ZIP
Affiliation for public queries	CanSino Biologics Inc.
Email address for public queries	ruijie.wang@cansinotech.com
Phone number for public queries	+8615620952966
Scientific Queries
Name of Contact for scientific queries	Dr. Ruijie Wang
Address for scientific queries	Address: 185, South Avenue, TEDA West District, Tianjin, China
City	Tianjin
Country	China
ZIP
Affiliation of scientific queries contact	CanSino Biologics Inc.
Email address for scientific queries	ruijie.wang@cansinotech.com
4. IRB & Regulatory
Ethical Approval number	06/KEP-RSHU/VII/2023 dan 12/KEP-RSHU/X/2023 (RSHU) dan 102/KEP/2023 (RS UNAIR)
Name of Ethics committee	Komite Etik Penelitian RS Husada Utama dan Komite Etik Penelitian RS Universitas Airlangga
Date of Ethic approval	07-07-2023
Contact details of Ethic Committee (phone, email, and office)	Komite Etik Penelitian RS Husada Utama (keprshu@gmail.com) dan Komite Etik Penelitian RS Universitas Airlangga (kepk@rsua.unair.ac.id).
Number of Persetujuan Pelaksanaan Uji Klinik (PPUK)/Persetujuan Protokol Uji BE (PPUB)	RG.01.06.1.3.10.23.43
5. Status
Countries of recruitment	Indonesia
Study sites in Indonesia	Rumah Sakit Husada Utama dan Rumah Sakit Universitas Airlangga
Recruitment status	Complete
Date of first enrollment	29-12-2023
Targeted Sample size	01880 -
Number of enrolled participants	Not yet enrolling
Date of study completion (last participant, last visit)
6. Study Design & Purpose
Primary health condition(s) or problem(s) studied (e.g., depression, breast cancer,medication error)	Adults aged 18 to 55 years
Purpose of the study	Prevention
Study type	Interventional
Interventional Study category	Clinical trial
Study phase	Phase 3
Method of allocation	Randomized allocation
Description of the allocation concealment mechanism and sequence generation	Lot 1: Lot 2: Lot 3: Control Group dengan perbandingan 1:1:1:1
Masking	Double Blinded (All parties excluede the specific unblinded team such as vaccine administrator and vaccine packing crew)
Study intervention (study arm)	Menhycia [Group ACYW135 Meningococcal Conjugate Vaccine (CRM197)] (MCV4)
Control intervention (control arm)	MENVEO [Meningococcal (Groups A, C, Y, and W-135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine]
Intervention assignment	Parallel
7. Eligibility Criteria
Gender inclusion criteria	Male, Female
Minimum age	18
Maximum age	55
Inclusion criteria	Participants aged 18-55 years old at the time of screening, who are in good health condition as determined by the study clinician, participants who have not been vaccinated with any meningococcal vaccines (including but not limited to meningococcal group A and C conjugate vaccine, meningococcal group A and C polysaccharide vaccine, Group ACYW135 Meningococcal polysaccharide/conjugate vaccine), the participant or participant’s legal guardian signs the informed consent form (ICF) and participant agrees to comply with the requirements of protocol and finish the 1-year follow-up, Participants who are willing to discuss medical history with investigators or doctors and allow access to all medical records relevant to this trial, Participants with child-bearing potential who are willing to practice adequate contraception methods from signing the ICF to 12 months after vaccination, This includes: abstinence from penile-vaginal intercourse, hormonal contraceptives such as oral contraceptives (the pill), injectables, implants, patches or estrogen vaginal ring (a ring-shaped hormonal contraceptive device that is used inside the vagina), Intrauterine device (IUD/Spiral), Male partner sterilization (vasectomy) prior to the female subject’s entry into the study, and this male is the sole partner for that subject, Male condom combined with a vaginal spermicide (a substance that can kill the sperm cells inside the vagina) or female diaphragm, whether with or without a vaginal spermicide, be able to communicate well with the investigator, and to understand and comply with the requirements of this clinical trial.
Exclusion criteria	Axillary temperature >37.5°C (99°F), have congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc., A history of epilepsy, convulsions or history/family history of mental illness, have meningitis or a history of meningitis illness, positive result of urine pregnancy test (also required for women within one year of menopause), lactating women, or participant /his partner is planning to become pregnant within 1 year, Hypersensitivity to a component or excipient of the vaccine used in this clinical trial (mainly: group A, C, Y or W135 meningococcal capsular polysaccharide, diphtheria toxoid or diphtheria antigen, sucrose, mannitol, sodium chloride, dipotassium hydrogen phosphate trihydrate, potassium dihydrogen phosphate), in the past 6 months (internal time < 6 months), participants have received immunosuppressive treatment, cytotoxic treatment, glucocorticoid treatment, etc. (excluding local treatment, surface treatment of acute non-concurrent dermatitis, spray treatment of allergic rhinitis), received or plan to receive blood/plasma products or immunoglobulins throughout the study period or 60 days prior to study vaccination, use of non-prescription drugs such as antipyretic (e.g., acetaminophen) and anti-inflammatory drugs (e.g., ibuprofen, naproxen etc.) within 12 hours before the administration of vaccine, have severe hypertension that is not controlled by medication (at the time of field measurement: systolic blood pressure ≥ 160 mmHg and diastolic blood pressure ≥ 100 mmHg), suffering from a severe chronic disease or a condition that is in a progressive stage and cannot be well controlled, such as thyroid disease, participants with known or suspected diseases that are judged by the investigator to affect the vaccination assessment, for example, acute infectious diseases, severe respiratory disease, severe cardiovascular disease, severe allergic skin disease etc, history of serious adverse reactions associated with the vaccine and/or history of severe allergic reactions (e.g., systemic allergic reactions) to any component of the study vaccine, Immunocompromised individuals with known or suspected immunodeficiency as determined by medical history and/or physical examination (e.g., HIV infection, history of pancreatic, liver, spleen, kidney disease or history of resection), bleeding constitution or condition associated with prolonged bleeding for which intramuscular injection is contraindicated in the opinion of the investigator, administration of live attenuated vaccine within 14 days or other vaccines within 7 days, participation in other studies involving interventional studies within 28 days prior to screening and/or during study participation, according to the judgment of the investigator, participants could be excluded due to various medical, psychological, social or other conditions that are contrary to the trial protocol or that affect the subject's ability to sign informed consent, investigator site staff directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members，sponsor staff and their respective family members.
8. Study Outcome
Primary Outcome
Name of primary outcome	To evaluate the lot-to-lot consistency for 3 lots of Group ACYW135 Meningococcal Conjugate Vaccine (CRM197) (MCV4) administered in single dose immunization schedule, with respect to its immunogenicity, to demonstrate that the immune response induced by a single dose of MCV4 is noninferior to the immune response induced by a single dose of MENVEO, in ACYW135 vaccine-naïve subjects only, immune response shall be measured by serum bactericidal activity assays with rabbit complement (rSBA titre) against serogroup A, C, W and Y strains, to evaluate the safety profile of MCV4 in people aged 18 to 55 years.
Metric/method of measurement	Geometric mean titers (GMTs), Seroconversion rate, serum bactericidal activity assays, and safety evaluation.
Timepoint(s) of measurement	The geometric mean titer (GMT) of serogroup A, C, Y and W135 meningococcal rSBA titer on day 30 post vaccination in all participants, The seroconversion rate of serogroup A, C, Y, and W135 meningococcal rSBA titer on day 30 post vaccination, Seroconversion rate for serogroup A, C, Y and W135 was defined as post-vaccination rSBA titers ≥ 1:8 for subjects with pre-vaccination titer < 1:8 or at least 4-fold increase in rSBA titers from pre- to post-vaccination for subjects with pre-vaccination titer ≥ 1:8, The incidence of adverse reactions (ARs) within 7 days post vaccination in all participants.
Secondary outcome 1
Name of secondary outcome 1 (SO1)	To evaluate the immuno-persistence of MCV4 in people aged 18 to 55 years
Metric/method of measurement (SO1)	Geometric mean titers (GMTs), Seroconversion rate, and serum bactericidal activity assays
Timepoint(s) of measurement (SO1)	The geometric mean fold increase (GMI) and the proportion of GMT ≥ 1:128 of serogroup A, C, Y and W135 meningococcal rSBA titer on day 30 post vaccination in all participants. The incidence of ARs and adverse events (AEs) within 30 days post vaccination in all participants. The incidence of ARs within 30 min post vaccination in all participants. The incidence of serious adverse events (SAEs) within 365 days post vaccination in all participants. The GMT, GMI and the proportion of GMT ≥ 1:128 of serogroup A, C, Y and W135 meningococcal antibodies on day 90, day 180 and day 365 post vaccination in the 480 subjects (Immunopersistence group).
9. Study Results
Brief summary of study results
Date of results summaries
Participant flow
Baseline characteristic	Participants aged 18-55 years old at the time of screening, who are in good health condition as determined by the study clinician, participants who have not been vaccinated with any meningococcal vaccines (including but not limited to meningococcal group A and C conjugate vaccine, meningococcal group A and C polysaccharide vaccine, Group ACYW135 Meningococcal polysaccharide/conjugate vaccine), the participant or participant’s legal guardian signs the informed consent form (ICF) and participant agrees to comply with the requirements of protocol and finish the 1-year follow-up, Participants who are willing to discuss medical history with investigators or doctors and allow access to all medical records relevant to this trial, Participants with child-bearing potential who are willing to practice adequate contraception methods from signing the ICF to 12 months after vaccination, This includes: abstinence from penile-vaginal intercourse, hormonal contraceptives such as oral contraceptives (the pill), injectables, implants, patches or estrogen vaginal ring (a ring-shaped hormonal contraceptive device that is used inside the vagina), Intrauterine device (IUD/Spiral), Male partner sterilization (vasectomy) prior to the female subject’s entry into the study, and this male is the sole partner for that subject, Male condom combined with a vaginal spermicide (a substance that can kill the sperm cells inside the vagina) or female diaphragm, whether with or without a vaginal spermicide, be able to communicate well with the investigator, and to understand and comply with the requirements of this clinical trial.
Adverse events
Outcome measures
10. Publication
URL hyperlink(s) related to results and publications
IPD sharing statement (Statement regarding the intended sharing of deidentified individual clinical trial participant-level data (IPD))	Undecided
Plan for IPD sharing (what IPD will be shared, when, by what mechanism, with whom, and for what types of analyses)
Other important informations	N/A