Safety and Immunogenicity of a Chlamydia Vaccine CTH522

NCT ID: NCT03926728

Last Updated: 2024-08-22

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

65 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-17

Study Completion Date

2022-02-22

Brief Summary

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CHLM-02 was a phase I, double-blind, randomized, placebo-controlled trial of the chlamydia vaccine CTH522. 65 trial participants were randomized into 12 groups and six cohorts (A1 to F2). Cohorts A to E received three intramuscular (IM) injections of CTH522 (Day 0, 28, and 112). Cohorts A to D received CTH522 adjuvanted with Cationic Adjuvant Formulation (CAF®) 01 IM in two doses (85µg \[A to C\] or 15µg \[D\]). Cohort E received 85µg CTH522 adjuvanted with CAF®09b. Cohorts B and C received unadjuvanted CTH522 boost via the topic ocular (TO) or intradermal (ID) route, respectively, jointly with the second and third IM vaccinations. Cohort F received placebo. The effect of mucosal recall on eye immunity with TO CTH522 or placebo was assessed Day 140.

Detailed Description

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This trial was a phase I, double-blind, parallel, randomised, and placebo-controlled trial of the chlamydia vaccine CTH522 in healthy adults.

It was planned to randomize 66 subjects but only 65 subjects were randomized. Cohorts A-D investigated CTH522-CAF01 administered IM in two doses (85 mcg and 15 mcg). Cohort E investigated CTH522-CAF09b administered IM in one dose (85 mcg). Cohort F was the placebo group. The enrolled subjects were to complete 12 trial visits. All subjects in the active cohorts (cohort A-E) were to receive three IM injections of the adjuvanted CTH522 and some (cohort B and C) were to 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 cohorts were to receive TO administration as a boost at Day 140 of either the non-adjuvanted CTH522 (12 mcg in each eye) or placebo.

* Cohort A received three IM vaccination of 85 mcg CTH522-CAF01. This cohort was divided into two groups: A1 received ID placebo at Day 28 and Day 112, and TO placebo at Day 140, while A2 received TO placebo at Day 28 and Day 112, and non-adjuvanted TO CTH522 boost at Day 140.
* Cohort B received three IM vaccinations of 85 mcg CTH522-CAF01. This cohort was divided into two groups: B1 received TO vaccination of the non-adjuvanted CTH522 at Day 28 and 112 and TO placebo at Day 140, while B2 received the same for Day 28 and 112, but non-adjuvanted TO CTH522 boost at Day 140. The two additional TO doses of CTH522 (12 mcg in each eye) were administered in each eye. The rationale for this schedule was to investigate the impact of simultaneous TO administration of the antigen on the immunogenicity results.
* Cohort C received three IM vaccinations of 85 mcg CTH522-CAF01. This cohort was divided into two groups: C1 received ID vaccination of the non-adjuvanted 24 mcg CTH522 at Day 28 and 112 and TO placebo at Day 140, while C2 received the same for Day 28 and 112, but TO 12 mcg CTH522 boost in each eye at Day 140. The rationale for this schedule was to investigate the impact of simultaneous ID administration of the antigen on the immunogenicity results.
* Cohort D received three IM vaccinations of 15 mcg CTH522-CAF01. The rationale for the A and D cohorts was to investigate the impact of the two IM CTH522 doses on the immunogenicity results.
* Cohort E received three IM vaccinations of 85 mcg CTH522-CAF09b. The rationale for the A and E cohorts was to investigate the impact of the adjuvant on the immunogenicity results.
* Cohort F received placebo in the form of 0.9% NaCl saline (IM, ID and TO).

Conditions

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Trachoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Cohort A 85 mcg CTH522-CAF01

Cohort A received three IM vaccination of 85 mcg CTH522-CAF01 (Day 0, 28, and 112). This cohort was divided into two groups: Cohort A1 receives placebo at Day 28, 112, and 140, while cohort A2 received placebo at Day 28 and 112, but non-adjuvanted TO CTH522 boost at Day 140.

Group Type EXPERIMENTAL

CTH522-CAF01 IM

Intervention Type BIOLOGICAL

On-site reconstitution of IMPs is performed by mixing 85 mcg 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.

CTH522 TO

Intervention Type BIOLOGICAL

24 mcg CTH522 (12 mcg 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.

Placebo (Saline)

Intervention Type BIOLOGICAL

Placebo only given as IM, ID and TO.

Cohort B 85 mcg CTH522-CAF01 + TO CTH522

Cohort B received three IM vaccination of 85 mcg CTH522-CAF01 (Day 0, 28, and 112). This cohort was divided into two groups: Cohort B1 received TO vaccination of the non-adjuvanted CTH522 at Day 28 and 112 and TO placebo at Day 140, while cohort B2 received the same for Day 28 and 112, but non-adjuvanted TO CTH522 boost at Day 140.

Group Type EXPERIMENTAL

CTH522-CAF01 IM

Intervention Type BIOLOGICAL

On-site reconstitution of IMPs is performed by mixing 85 mcg 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.

CTH522 TO

Intervention Type BIOLOGICAL

24 mcg CTH522 (12 mcg 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.

Placebo (Saline)

Intervention Type BIOLOGICAL

Placebo only given as IM, ID and TO.

Cohort C 85 mcg CTH522-CAF01 + ID CTH522

Cohort C received three IM vaccination of 85 mcg CTH522-CAF01 (Day 0, 28, and 112). This cohort was divided into two groups: Cohort C1 received ID vaccination of the non-adjuvanted CTH522 at Day 28 and 112 and TO placebo at Day 140, while cohort C2 received the same for Day 28 and 112, but TO CTH522 boost at Day 140.

Group Type EXPERIMENTAL

CTH522-CAF01 IM

Intervention Type BIOLOGICAL

On-site reconstitution of IMPs is performed by mixing 85 mcg 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.

CTH522 ID

Intervention Type BIOLOGICAL

24 mcg 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.

CTH522 TO

Intervention Type BIOLOGICAL

24 mcg CTH522 (12 mcg 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.

Placebo (Saline)

Intervention Type BIOLOGICAL

Placebo only given as IM, ID and TO.

Cohort D 15 mcg CTH522-CAF01

Cohort D received three IM vaccination of 15 mcg CTH522-CAF01 (Day 0, 28, and 112). This cohort was divided into two groups: Cohort D1 received TO placebo given on Day 28, 112, and 140, while cohort D2 received ID placebo given on Day 28 and 112 and TO unadjuvanted CTH522 on Day 140.

Group Type EXPERIMENTAL

CTH522-CAF01 IM

Intervention Type BIOLOGICAL

On-site reconstitution of IMPs is performed by mixing 85 mcg 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.

CTH522 TO

Intervention Type BIOLOGICAL

24 mcg CTH522 (12 mcg 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.

Placebo (Saline)

Intervention Type BIOLOGICAL

Placebo only given as IM, ID and TO.

Cohort E 85 mcg CTH522-CAF09b

Cohort E received three IM vaccination of 85 mcg CTH522-CAF09b (Day 0, 28, and 112). This cohort was divided into two groups: Cohort E1 received TO placebo given on Day 28, 112, and 140, while cohort E2 received ID placebo given on Day 28 and 112 and TO unadjuvanted CTH522 on Day 140.

Group Type EXPERIMENTAL

CTH522-CAF09b IM

Intervention Type BIOLOGICAL

On-site reconstitution of IMPs is performed by mixing 85 mcg 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.

CTH522 TO

Intervention Type BIOLOGICAL

24 mcg CTH522 (12 mcg 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.

Placebo (Saline)

Intervention Type BIOLOGICAL

Placebo only given as IM, ID and TO.

Cohort F Placebo

Cohort F received three IM vaccinations of placebo in form of 0.9% NaCl saline (Day 0, 28, and 112).This cohort was divided into two groups: Cohort F1 received TO placebo given on Day 28, 112, and 140, while cohort F2 received ID placebo given on Day 28 and 112 and TO placebo on Day 140.

Group Type PLACEBO_COMPARATOR

Placebo (Saline)

Intervention Type BIOLOGICAL

Placebo only given as IM, ID and TO.

Interventions

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CTH522-CAF01 IM

On-site reconstitution of IMPs is performed by mixing 85 mcg 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.

Intervention Type BIOLOGICAL

CTH522-CAF09b IM

On-site reconstitution of IMPs is performed by mixing 85 mcg 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.

Intervention Type BIOLOGICAL

CTH522 ID

24 mcg 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.

Intervention Type BIOLOGICAL

CTH522 TO

24 mcg CTH522 (12 mcg 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.

Intervention Type BIOLOGICAL

Placebo (Saline)

Placebo only given as IM, ID and TO.

Intervention Type BIOLOGICAL

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 hormone releasing 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Imperial College London

OTHER

Sponsor Role collaborator

Statens Serum Institut

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alvaro Borges, MD

Role: STUDY_DIRECTOR

Statens Serum Institut

Katrina Pollock, MD

Role: PRINCIPAL_INVESTIGATOR

Imperial Clinical Research Facility Hammersmith Hospital

Lina S Stoey, MPH

Role: STUDY_CHAIR

Statens Serum Institut

Pernille N Tingskov, BS

Role: STUDY_CHAIR

Statens Serum Institut

Rebecca B Dohn, Pharm

Role: STUDY_CHAIR

Statens Serum Institut

Locations

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NIHR Imperial Center for Translational and Experimental Medicine

London, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Pollock KM, Borges AH, Cheeseman HM, Rosenkrands I, Schmidt KL, Sondergaard RE, Day S, Evans A, McFarlane LR, Joypooranachandran J, Amini F, Skallerup P, Dohn RB, Jensen CG, Olsen AW, Bang P, Cole T, Schronce J, Lemm NM, Kristiansen MP, Andersen PL, Dietrich J, Shattock RJ, Follmann F. An investigation of trachoma vaccine regimens by the chlamydia vaccine CTH522 administered with cationic liposomes in healthy adults (CHLM-02): a phase 1, double-blind trial. Lancet Infect Dis. 2024 Aug;24(8):829-844. doi: 10.1016/S1473-3099(24)00147-6. Epub 2024 Apr 11.

Reference Type DERIVED
PMID: 38615673 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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CHLM-02

Identifier Type: -

Identifier Source: org_study_id

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