Safety and Immunogenicity of a Chlamydia Vaccine CTH522 (CHLM-02)

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

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.

Study Overview

• Status: Completed
• Conditions: Trachoma
• Intervention / Treatment: Biological: CTH522-CAF01 IM; Biological: CTH522 TO; Biological: Placebo (Saline); Biological: CTH522 ID; Biological: CTH522-CAF09b IM

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12
    • NIHR Imperial Center for Translational and Experimental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: 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.; 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.; Biological: Placebo (Saline); Placebo only given as IM, ID and TO.
Experimental: 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.	Biological: 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.; 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.; Biological: Placebo (Saline); Placebo only given as IM, ID and TO.
Experimental: 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.	Biological: 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.; 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.; Biological: Placebo (Saline); Placebo only given as IM, ID and TO.; 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.
Experimental: 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.	Biological: 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.; 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.; Biological: Placebo (Saline); Placebo only given as IM, ID and TO.
Experimental: 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.	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.; Biological: Placebo (Saline); Placebo only given as IM, ID and TO.; 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.
Placebo Comparator: 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.	Biological: Placebo (Saline); Placebo only given as IM, ID and TO.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Solicited Local Injection Site Reactions	Local injection site reactions after intramuscular vaccination. Solicited local injection site reactions are defined as erythema, pruritus, pain, tenderness, swelling, and warmth.	Visit 2 (Day 0) plus 14 Days
Solicited Local Injection Site Reactions	Local injection site reactions after intramuscular vaccination (participants also received intradermal or topical ocular administration of CTH522 or placebo). Solicited local injection site reactions are defined as erythema, pruritus, pain, tenderness, swelling, and warmth.	Visit 4 (Day 28) plus 14 Days
Solicited Local Injection Site Reactions	Local injection site reactions after intramuscular vaccination (participants also received intradermal or topical ocular administration of CTH522 or placebo). Solicited local injection site reactions are defined as erythema, pruritus, pain, tenderness, swelling, and warmth.	Visit 7 (Day 112) plus 14 Days
Solicited Local Ocular Reactions	Local ocular reactions after topical ocular administration of CTH522 or placebo. Solicited local ocular reactions are defined as watering eyes, swelling of eyelid, eye redness, and eye discomfort.	Visit 4 (Day 28) plus 14 Days
Solicited Local Ocular Reactions	Local ocular reactions after topical ocular administration of CTH522 or placebo. Solicited local ocular reactions are defined as watering eyes, swelling of eyelid, eye redness, and eye discomfort.	Visit 7 (Day 112) plus 14 Days
Solicited Local Ocular Reactions	Local ocular reactions after topical ocular administration of CTH522 or placebo. Solicited local ocular reactions are defined as watering eyes, swelling of eyelid, eye redness, and eye discomfort.	Visit 9 (Day 140) plus 14 Days
Solicited Systemic Reactions	Systemic reactions after vaccinations. Solicited systemic reactions are defined as oral temperature > 38.3°C, chills, myalgia, and rash.	Visit 2 (Day 0) plus 14 Days
Solicited Systemic Reactions	Systemic reactions after vaccinations. Solicited systemic reactions are defined as oral temperature > 38.3°C, chills, myalgia, and rash.	Visit 4 (Day 28) plus 14 Days
Solicited Systemic Reactions	Systemic reactions after vaccinations. Solicited systemic reactions are defined as oral temperature > 38.3°C, chills, myalgia, and rash.	Visit 7 (Day 112) plus 14 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity (4-fold Increase From Baseline)	Frequency of 4-fold increase seroconversion from baseline for anti-CTH522 IgG after vaccinations.	Day 14, 28, 42, 56, 112, 126, 140, 154, 238
Immunogenicity (10-fold Increase From Baseline)	Frequency of 10-fold increase seroconversion from baseline for anti-CTH522 IgG after vaccinations.	Day 14, 28, 42, 56, 112, 126, 140, 154, 238

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory - immunogenicity	Systemic and ocular antibodies: cell-mediated immune response, antibody responses measured by T- and B-cell Elispot, serum neutralising antibodies against serovars D-G. Isolation and characterisation of CTH522-antigen-specific memory B-cells in the systemic compartments (dependent on the elicited specific memory T- and B-cell numbers)	Visit 2 (Day 0) to Visit 12 (Day 238); except for Visit 3 (Day 14) for ocular strip

Collaborators and Investigators

• Sponsor: Statens Serum Institut
• Collaborators: Imperial College London
• Investigators: Study Director: Alvaro Borges, MD, Statens Serum Institut; Study Chair: Lina S Stoey, MPH, Statens Serum Institut; Study Chair: Pernille N Tingskov, BS, Statens Serum Institut; Study Chair: Rebecca B Dohn, Pharm, Statens Serum Institut; Principal Investigator: Katrina Pollock, MD, Imperial Clinical Research Facility Hammersmith Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2020
• Primary Completion (Actual): February 22, 2022
• Study Completion (Actual): February 22, 2022

Study Registration Dates

• First Submitted: April 15, 2019
• First Submitted That Met QC Criteria: April 23, 2019
• First Posted (Actual): April 24, 2019

Study Record Updates

• Last Update Posted (Actual): August 22, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Chlamydia; CTH522; C. Trachomatis
• Additional Relevant MeSH Terms: Infections; Communicable Diseases; Sexually Transmitted Diseases; Eye Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Conjunctivitis; Conjunctival Diseases; Corneal Diseases; Chlamydiaceae Infections; Sexually Transmitted Diseases, Bacterial; Eye Infections, Bacterial; Eye Infections; Conjunctivitis, Bacterial; Urogenital Diseases; Genital Diseases; Chlamydia Infections; Trachoma
• Other Study ID Numbers: CHLM-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No