Safety and Immunogenicity of a Chlamydia Vaccine CTH522

Study Overview
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Brief Summary
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The present trial is a phase I, double-blind, parallel, randomised, and placebo-controlled trial of a chlamydia vaccine CTH522. Sixty-six subjects will be randomly assigned into six cohorts and are to receive four vaccination, in total of 12 trial visits. Cohorts A-D investigates CTH522-CAF01 administered IM in two doses (85 µg and 15 µg). Cohort E investigate CTH522-CAF09b also administered IM in one dose (85 µg). Cohort E is the placebo group. All subjects will receive a TO administration as a boost at Day 140 (4th vaccination). The TO boost will be non-adjuvanted CTH522 (12µg in each eye) or placebo. Nine subjects in each of cohorts A-E will receive the active boost (i.e. CTH522), three subjects will receive the placebo.

Detailed Description
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This trial is a phase I, double-blind, parallel, randomised, and placebo-controlled trial of the chlamydia vaccine CTH522 in healthy adults. It is planned to randomly assign 66 subjects into six cohorts. Cohorts A-D investigate CTH522-CAF01 administered IM in two doses (85 μg and 15 μg). Cohort E investigates CTH522-CAF09b administered IM in one dose (85 μg). Cohort F is the placebo group. The enrolled subjects will complete 12 trial visits. All subjects in the active groups (cohort A-E) will receive three IM injections of the adjuvanted CTH522 and some (cohort B and C) will receive the non-adjuvanted CTH522 via the TO or ID route (given at the same time as the 2nd and 3rd IM vaccinations). All active groups will receive TO administration as a boost at Day 140 of either the non-adjuvanted CTH522 (12 μg in each eye) or placebo. Cohort A will receive three IM vaccination of 85μg CTH522-CAF01. This cohort is divided into two groups: A1 will receive ID placebo at Day 28 + Day 112, and TO placebo at Day 140, while A2 will receive TO placebo at Day 28 + Day 112, and non-adjuvanted TO CTH522 boost at Day 140. Cohort B will receive three IM vaccinations of 85 μg CTH522-CAF01. This cohort is divided into two groups: B1 will receive TO vaccination of the non-adjuvanted CTH522 at Day 28 and 112 and TO placebo at Day 140, while B2 will receive the same for Day 28 and 112, but non-adjuvanted TO CTH522 boost at Day 140. The two additional TO doses of CTH522 (12 μg in each eye) are administered in each eye. The rationale for this schedule is to investigate the impact of simultaneous TO administration of the antigen on the immunogenicity results. Cohort C will receive three IM vaccinations of 85 μg CTH522-CAF01. This cohort is divided into two groups: C1 will receive ID vaccination of the non-adjuvanted 24 μg CTH522 at Day 28 and 112 and TO placebo at Day 140, while C2 will receive the same for Day 28 and 112, but TO 12 μg CTH522 boost in each eye at Day 140. The rationale for this schedule is to investigate the impact of simultaneous ID administration of the antigen on the immunogenicity results. Cohort D will receive three IM vaccinations of 15 μg CTH522-CAF01. The rationale for the A and D cohorts is to investigate the impact of the two IM CTH522 doses on the immunogenicity results. Cohort E will receive three IM vaccinations of 85 μg CTH522-CAF09b. The rationale for the A and E cohorts is to investigate the impact of the adjuvant on the immunogenicity results. Cohort F will receive only placebo in the form of 0.9% NaCl saline (IM, ID and TO).

Official Title
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A Phase I, Double-blind, Parallel, Randomised and Placebo-controlled Trial Investigating the Safety and Immunogenicity of a Chlamydia Vaccine, CTH522, in Healthy Adults

Conditions
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Trachoma

Intervention / Treatment
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* Biological: CTH522-CAF01 IM
* Biological: CTH522-CAF09b IM
* Biological: CTH522 ID
* Biological: CTH522 TO
* Biological: Placebo (Saline)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: IC1: Healthy males and females between 18-45 years old on the day of the first vaccination IC2: Has been properly informed about the trial and signed the consent form IC3: Is willing and likely to comply with trial procedures IC4: Is prepared to grant authorised persons access to his/her trial-related medical record IC5: Is willing to use acceptable contraceptive measures during the trial (two weeks before and two weeks after the trial). Heterosexually active female capable of becoming pregnant must agree to use hormonal contraception, intrauterine device, intrauterine hormonereleasing system, or to complete abstinence from at least two weeks before the first vaccination until at least two weeks after the last. Complete abstinence (defined as refraining from heterosexual intercourse) must be in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods), withdrawal and progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary mode of action are not acceptable methods of contraception Exclusion criteria: EX1: Is positive for C. trachomatis via urine PCR or has a known history of C. trachomatis EX2: Is positive for gonorrhoea via urine PCR test, or HIV, hepatitis B/C, syphilis via blood tests EX3: Has a significant active disease such as cardiac, liver, immunological, neurological, psychiatric or clinically significant abnormality of haematological or biochemical parameters EX4: Has BMI ≥ 35 kg/m2 EX5: Is currently participating in another clinical trial with an investigational or noninvestigational drug or device, or was treated with an investigational drug within 28 days before the first vaccination EX6: Has received, or plans to receive, any immunisation within 14 days of the start of the trial or during the trial immunisations EX7: Is currently receiving treatment with systemic immunosuppressive agents. Topical steroids are allowed unless applied to the IM or ID injection site EX8: Has a condition which in the opinion of the investigator is not suitable for participation in the trial EX9: Is known or confirmed to have an allergy to any of the vaccine constituents EX10: Is unable to refrain from the use of contact lenses. Contact lenses should be avoided two days before TO administration and for seven days later (longer if any ongoing local eye AE) EX11: Has any evident ocular disease upon ophthalmoscopic exam at screening or any medical history of ocular disease that, in the opinion of the investigator, may impact the subject's participation in the trial EX12: Is pregnant (positive pregnancy test) or breastfeeding or not willing to use contraception during the trial EX13: Has confirmed a history of pelvic inflammatory disease or significant gynaecological diseases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A - 85µg CTH522-CAF01<br>Cohorts A will receive three IM vaccination of 85µg CTH522-CAF01. This cohort is divided into two groups: A1 will receive placebo at DAY 28 + Day 112 + Day 140, while A2 will receives placebo at Day 28 + Day 112, but non-adjuvanted TO CTH522 boost at Day 140. | Biological: CTH522-CAF01 IM<br>* On-site reconstitution of IMPs is performed by mixing 85 microgram CTH522 with CAF01. The preferred for IM is in the non-dominant deltoid muscle. IM injection will be performed with a 1-2 ml polypropylene Luer-Lok™ syringe via 23-25-gauge needle. The identity of the injected trial vaccine will be known to the clinical site staff dispensing and/or injecting the trial vaccine to the subject and by the unblinded trial monitor. The identity of the trial vaccine administered will remain unknown to the subject during the trial.<br>Biological: CTH522 TO<br>* 24 microgram CTH522 (12 microgram in each eye) TO administrations will be performed using a Gilson positive displacement pipette. The identity of vaccine will be known to the clinical site staff dispensing/administrating the trial vaccine to the subject and by the unblinded trial monitor. The identity of the trial vaccine administered will remain unknown to the subject during the trial.<br>Biological: Placebo (Saline)<br>* Placebo only given as IM, ID and TO<br>|
| Experimental: Cohort B - 85µg CTH522-CAF01+ TO CTH522<br>Cohort B will receive three IM vaccination of 85 µg CTH522-CAF01. This cohort is divided into two groups: B1 will receive TO vaccination of the non-adjuvanted CTH522 at Day 28 + Day 112 and TO placebo at Day 140, while B2 will receive the same for Day 28 + Day 112, but non-adjuvanted TO CTH522 boost at Day 140. The two additional doses TO CTH522 (12µg) is administered in each eye. The rationale for this cohort is to investigate the impact of simultaneous TO administration of the antigen on the immunogenicity results obtained. | Biological: CTH522-CAF01 IM<br>* On-site reconstitution of IMPs is performed by mixing 85 microgram CTH522 with CAF01. The preferred for IM is in the non-dominant deltoid muscle. IM injection will be performed with a 1-2 ml polypropylene Luer-Lok™ syringe via 23-25-gauge needle. The identity of the injected trial vaccine will be known to the clinical site staff dispensing and/or injecting the trial vaccine to the subject and by the unblinded trial monitor. The identity of the trial vaccine administered will remain unknown to the subject during the trial.<br>Biological: CTH522 TO<br>* 24 microgram CTH522 (12 microgram in each eye) TO administrations will be performed using a Gilson positive displacement pipette. The identity of vaccine will be known to the clinical site staff dispensing/administrating the trial vaccine to the subject and by the unblinded trial monitor. The identity of the trial vaccine administered will remain unknown to the subject during the trial.<br>Biological: Placebo (Saline)<br>* Placebo only given as IM, ID and TO<br>|
| Experimental: Cohort C - 85µg CTH522-CAF01+ID CTH522<br>Cohort C will receive three IM vaccination of 85 µg CTH522-CAF01. This cohort is divided into two groups: C1 will receive ID vaccination of the non-adjuvanted CTH522 at Day 28 + Day 12 and TO placebo at Day 140, while C2 will receive the same for Day 28 + Day 112, but TO CTH522 boost at Day 140. The two additional doses of non-adjuvanted CTH522 (24µg) is administered ID. The rationale for this cohort is to investigate the impact of simultaneous ID administration of the antigen on the immunogenicity results obtained. | Biological: CTH522-CAF01 IM<br>* On-site reconstitution of IMPs is performed by mixing 85 microgram CTH522 with CAF01. The preferred for IM is in the non-dominant deltoid muscle. IM injection will be performed with a 1-2 ml polypropylene Luer-Lok™ syringe via 23-25-gauge needle. The identity of the injected trial vaccine will be known to the clinical site staff dispensing and/or injecting the trial vaccine to the subject and by the unblinded trial monitor. The identity of the trial vaccine administered will remain unknown to the subject during the trial.<br>Biological: CTH522 ID<br>* 24 microgram CTH522 given ID is in the non-dominant deltoid muscle. ID with a 1 ml syringe via a 26-28 gauge needle using a NanoPass device or similar. The identity of the injected trial vaccine will be known to the clinical site staff dispensing and/or injecting the trial vaccine to the subject and by the unblinded trial monitor. The identity of the trial vaccine administered will remain unknown to the subject during the trial.<br>Biological: Placebo (Saline)<br>* Placebo only given as IM, ID and TO<br>|
| Experimental: Cohort D - 15µg CTH522-CAF01<br>Cohort D is the same as cohort A except that the dose for CTH522-CAF01 is 15µg. | Biological: CTH522-CAF01 IM<br>* On-site reconstitution of IMPs is performed by mixing 85 microgram CTH522 with CAF01. The preferred for IM is in the non-dominant deltoid muscle. IM injection will be performed with a 1-2 ml polypropylene Luer-Lok™ syringe via 23-25-gauge needle. The identity of the injected trial vaccine will be known to the clinical site staff dispensing and/or injecting the trial vaccine to the subject and by the unblinded trial monitor. The identity of the trial vaccine administered will remain unknown to the subject during the trial.<br>Biological: CTH522 TO<br>* 24 microgram CTH522 (12 microgram in each eye) TO administrations will be performed using a Gilson positive displacement pipette. The identity of vaccine will be known to the clinical site staff dispensing/administrating the trial vaccine to the subject and by the unblinded trial monitor. The identity of the trial vaccine administered will remain unknown to the subject during the trial.<br>Biological: Placebo (Saline)<br>* Placebo only given as IM, ID and TO<br>|
| Experimental: Cohort E - 85µg CTH522-CAF09b<br>Cohort E is the same as cohort A except that the adjuvant is CAF09b and not CAF01. The rationale for the A, D and E cohorts is to investigate the impact of the CTH522 dose and adjuvant on the immunogenicity results. | Biological: CTH522-CAF09b IM<br>* On-site reconstitution of IMPs is performed by mixing 85 microgram CTH522 with CAF09b. The preferred for IM is in the non-dominant deltoid muscle. IM injection will be performed with a 1-2 ml polypropylene Luer-Lok™ syringe via 23-25-gauge needle. The identity of the injected trial vaccine will be known to the clinical site staff dispensing and/or injecting the trial vaccine to the subject and by the unblinded trial monitor. The identity of the trial vaccine administered will remain unknown to the subject during the trial.<br>Biological: Placebo (Saline)<br>* Placebo only given as IM, ID and TO<br>|
| Placebo Comparator: Cohort F - Placebo<br>Cohort F will receive only placebo in form of 0.9% NaCl saline. | Biological: Placebo (Saline)<br>* Placebo only given as IM, ID and TO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local injection reactions | Local injection site reactions after intramuscular and intradermal vaccination | Visit 2 (Day 0) to Visit 12 (Day 238) | 
| Local ocular reactions | Local ocular reactions after topical ocular vaccination | Visit 2 (Day 0) to Visit 12 (Day 238) | 
| Systemic reactions | Systemic reactions after vaccinations | Visit 2 (Day 0) to Visit 12 (Day 238) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary - immunogenicity | Seroconversion for anti-CTH522 IgG at any time points after vaccinations of CTH522 | Visit 2 (Day 0) to Visit 12 (Day 238); except for Visit 10 (Day 143) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CTH522, Chlamydia, C. Trachomatis