Phase 1 N=50 Randomized Double-blind Prevention

Dosage-Escalation Study of the Safety and Immunogenicity of a Novel Rabies Vaccine ChAd155-RG vs. the Comparator RABAVERT Vaccine in Healthy Adult Subjects

Rabies · Rabies Immunisation

Bottom Line

View on ClinicalTrials.gov: NCT04019444 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Apr 2024

Primary outcome: Primary: Number and Percentage of Participants With Solicited Injection Site Reactogenicity Events in Each Treatment Arm and Overall — 3; 2; 0; 0 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: ChAd155-RG (Biological); Placebo (Other); Rabies Vaccine (Biological)
Age: Adult · 18+ yrs
Sex: All
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Primary completion: Mar 2023

Outcome Measures

Outcome	Result	p-value
PRIMARY Number and Percentage of Participants With Solicited Injection Site Reactogenicity Events in Each Treatment Arm and Overall	3; 2; 0; 0; 5; 10	—
PRIMARY Number and Percentage of Participants With Solicited Systemic Reactogenicity Events in Each Treatment Arm and Overall	3; 1; 1; 4; 9; 5	—
PRIMARY Number and Percentage of Participants With Serious Adverse Events (SAEs) Considered Study Vaccine-Related in Each Treatment Arm and Overall	14; 14; 10; 12; 50; 0	—
PRIMARY Number and Percentage of Participants With Study Vaccine-related Lab Adverse Events (AEs) in Each Treatment Arm and Overall	8; 6; 3; 8; 25; 5	—
PRIMARY Number and Percentage of Participants With Unsolicited Study Vaccine-related Adverse Events (AEs) in Each Treatment Arm and Overall	14; 13; 10; 11; 48; 0	—
PRIMARY Number and Percentage of Participants With New Onset of a Chronic Medical Condition in Each Treatment Arm and Overall	0; 0; 0; 0; 0	—
PRIMARY Number and Percentage of Participants With Serious Adverse Events (SAEs) in Each Treatment Arm and Overall	14; 14; 10; 12; 50; 0	—
SECONDARY Percentage of Participants Seroconverting to Rabies Virus in Each Treatment Arm and Overall	0; 0; 0; 0; 0; 43	—
SECONDARY Rabies VNA Geometric Mean Titer	0.05; 0.05; 0.05; 0.05; 0.05; 0.05	—
SECONDARY Peak Rabies VNA Geometric Mean Titer	0.94; 0.90; 1.65; 10.63; 1.79	—

Summary

This is a single-center, observer-blinded, dosage-escalation trial to evaluate the safety, tolerability, reactogenicity, and immunogenicity of ChAd155-RG compared with RABAVERT in rabies virus-naïve healthy male and non-pregnant female adult subjects ages 18-49. There are 4 dose groups: Group A will receive ChAd155-RG at the lower dosage (5x1010vp) on Day 1, then placebo injections on Days 8, 15, and 22; Group B will receive ChAd155-RG at the higher dosage (1x1011vp) on Day 1, then placebo injections on Days 8, 15, and 22; Group C will receive ChAd155-RG at the higher dosage (1x1011vp) on Days 1 and 15, and placebo injections on Days 8 and 22; Group D will receive RABAVERT at the standard dose (1 mL) on Days 1, 8, and 22, and a placebo injection on Day 15. Since this is a dosage-escalation study, sentinel subjects will be used at each dosage level before non-sentinel subjects will be enrolled. The study will be conducted at Emory University Vaccine and Treatment Evaluation Unit (VTEU). This trial is expected to take approximately 48 months to complete. The duration of each subject's participation is approximately 13 months, from recruitment through the last study visit. The primary objectives of this study are: 1) Assessment of the safety, tolerability, and reactogenicity of one dose of ChAd155-RG at 5x1010vp per dose, or one or two doses of ChAd155-RG at 1x1011vp per dose; 2) Comparison of the safety, tolerability, and reactogenicity of one or two doses of ChAd155-RG, with three doses of RABAVERT.

Eligibility Criteria

Inclusion Criteria

Must be a male or female aged 18-49 years old (inclusive) at the time of first vaccination.
Must be able to provide written informed consent.
Must have a body mass index (BMI) = / >18.5 and 11.6 g/dL, men >13.1 g/dL
White blood cells: >3,700 but 1,500 cells/mm^3
Absolute lymphocyte count: = / >850 cells/mm^3
Platelets: >139,000 but 12 months without other known or suspected cause for amenorrhea), or surgically sterile [hysterectomy, bilateral tubal ligation, bilateral oophorectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization)] with documented confirmation test = / >3 months after the procedure), are not required to use contraceptive methods.
Women of childbearing potential must use an acceptable method of contraception* from 28 days before the first vaccination until = / >60 days after the last vaccination.

*Acceptable methods of contraception include: prescription oral contraceptives, contraceptive injections, intrauterine device (IUD), implants, vaginal ring, double-barrier method, contraceptive patch, male partner who had a vasectomy at least 6 months prior to study enrollment, abstinence (defined as refraining from heterosexual intercourse during participation in this trial [from 28 days before the first vaccination until = / >60 days after the last vaccination]).

Female subjects must agree to not donate eggs (ova, oocytes) from the start of screening until = / >60 days after the last vaccination.
Male subjects who have not had a vasectomy* and are sexually active with a woman of childbearing potential must agree to use an acceptable method of contraception**.

*Men who have had a vasectomy must have had the procedure performed at least 6 months prior to study enrollment.

**Acceptable methods of contraception must be used from the first vaccination until = / >60 days after the last vaccination, and include: abstinence (defined as refraining from heterosexual intercourse with a female partner of childbearing potential during participation in this trial [from 28 days before the first vaccination until = / >60 days after the last vaccination]; a double-barrier method, such as condom with spermicidal foam/gel/film/cream/suppository and partner with occlusive cap (diaphragm, cervical/vault caps); if the female partner is using an acceptable method of contraception (see Inclusion Criterion #7), a single-barrier method for the male subject is acceptable.

Male subjects must agree to not donate sperm from the start of screening until = / >60 days after the last vaccination.
Must be available and willing to participate for the duration of this trial.
Must have a means to be contacted by telephone.

Exclusion Criteria

Was ever vaccinated with a licensed or investigational rabies vaccine* or was diagnosed with rabies exposure, infection, or disease.

*Includes RABAVERT and Imovax. Subject's verbal history will suffice.

Has a higher risk than the average US resident with regard to exposure to rabies, per the Rabavert package insert and rabies vaccination recommendations from the CDC*.
People at high risk of exposure to rabies, such as veterinarians, animal handlers, rabies laboratory workers, spelunkers, and rabies biologics production workers.
People whose activities bring them into frequent contact with rabies virus or with possibly rabid animals.
International travelers who are likely to come in contact with animals in parts of the world where rabies is common.
Was ever vaccinated with a licensed or investigational Ad vector or Ad vaccine.
Is currently taking chloroquine or hydroxychloroquine.
Was diagnosed with laboratory-confirmed COVID-19 (PCR or antigen-based test) in the preceding 28 days.
Positive serology for HIV antibody, HCV antibody, or Hepatitis B surface antigen (HBsAg).
Has known allergy or history of anaphylaxis or other serious adverse reaction to a vaccine or vaccine products*.

*Includi

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Data sourced from ClinicalTrials.gov (NCT04019444). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.