Safety and Effectiveness of BPL HRIG With Active Rabies Vaccine in Healthy Subjects

A Prospective, Randomized, Double-Blind Parallel-group, Non-inferiority Phase II/III Study of the Safety and Effectiveness of BPL HRIG With Co Administration of Active Rabies Vaccine in Healthy Subjects

A prospective, randomized, blinded, parallel-group, non-inferiority, phase II/III study of the safety and effectiveness of simulated post-exposure prophylaxis with BPL HRIG with co-administration of active rabies vaccine in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: HRIG; Biological: RabAvert; Drug: HyperRAB

Detailed Description

Each subject will undergo a total of 9 visits. Subjects' eligibility will be assessed at Screening, which can occur up to 28 days prior to dosing. Following a repeat eligibility check at Day 0, eligible subjects will be randomized and dosed with the randomized treatment (BPL HRIG + vaccine or Comparator HRIG + vaccine) on Day 0. Further assessments will be conducted on Days 3, 5, 7, 14, 28, 49 and the end of study assessment on Day 140. Vaccine will be administered on Day 0, 3, 7, 14 and 28.

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Prism Research
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able and willing to sign an informed consent form.
2. Healthy male or female subjects aged 18 - 75 years inclusive.
3. No previous exposure to rabies virus, rabies vaccine and/or rabies immunoglobulin.
4. No significant abnormalities in hematology, biochemistry, or urinalysis according to the Principal Investigator's judgment.
5. No significant abnormalities in ECG according to the Investigator's judgment.
6. Females of child-bearing potential (defined from the onset of menstruation to one-year post- menopause and not surgically sterilized) who are (or become) sexually active must agree to practice contraception by using a highly effective (>98%) method for the duration of the study.
7. Females of child-bearing potential (defined from the onset of menstruation to one-year post- menopause and not surgically sterilized) must have a negative result on a serum at screening visit and a urine HCG-based pregnancy test at Day 0.

Exclusion Criteria

1. Female subjects who are pregnant and/or lactating.
2. History of live virus vaccination, e.g., measles, mumps, varicella or rubella vaccine, within the last 3 months.
3. Planned live virus vaccination, e.g., measles, mumps, varicella or rubella vaccine, within the 3 months after Day 0.
4. History of anaphylactic or anaphylactoid hypersensitivity reactions to chicken egg; history of mild allergic reactions to chicken egg, e.g., skin rash only, is not an exclusion criterion
5. History of hypersensitivity reaction to any of the following components of active rabies vaccine (US-FDA approved) e.g.: neomycin, bovine gelatin, trace amounts of chicken protein, chlortetracycline, and amphotericin B and in accordance with the product insert of the vaccine.
6. History of life-threatening allergy, anaphylactic reaction, or systemic response to human plasma derived products.
7. History of life-threatening allergy to blood or blood products.
8. Fever at the time of the start of the injection (oral temperature >38ºC.) or acute illness at the time of the start of the injection. Subjects with fever on Day 0 may have entry to the study re-scheduled.
9. History of or ongoing bleeding disorder.
10. Previous organ transplant recipient.
11. Ongoing immunosuppressive illness.
12. Clinically significant illnesses including: cardiac, hepatic, renal, endocrine, neurological, hematological, neoplastic, immunological, skeletal or other) that in the opinion of the investigator, could interfere with the safety, compliance or other aspects of this study.
13. All types of malignancies except for basal and squamous cell (scaly or plate-like) skin cancer, in- situ cervical carcinoma must be in remission for a minimum of 5 years prior to Day 0. For non-melanoma skin cancers and carcinoma in-situ of the cervix may be enrolled if treated and cured at the time of screening.
14. Evidence of active systemic infection that requires treatment with antibiotics within 2 weeks prior to Day 0.

15. Currently receiving or have received within the past 6 months (prior to Day 0):

    • immunosuppressive drugs
    • immunomodulatory drugs
16. Currently receiving or have received oral or IV steroids within 14 days (prior to DAY 0) or expected to require oral or IV steroids during the study.
17. Evidence of uncontrolled hypertension (systolic blood pressure of >150 mmHg, and/or diastolic blood pressure of >100 mmHg).
18. Heart rate >120/min.
19. Weight > 95.5 kg
20. History of IgA deficiency.
21. Is positive for any of the following at screening: serological test for HIV 1&2, HCV or HBsAg.
22. Presence of psychiatric disorder, other mental disorder or any other medical disorder which might impair the subject's ability to give informed consent or to comply with the requirements of the study protocol.
23. Previous enrollment in this study.
24. Participation in an interventional clinical trial within 30 days prior to baseline visit (Day 0).
25. Evidence of alcohol abuse or history of alcohol abuse or illegal and/or legally prescribed drugs in the past 2 years.
26. Any other factor that, in the opinion of the investigator, would prevent the subject from complying with the requirements of the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BPL HRIG + RabAvert; 20 IU/kg dose HRIG + active rabies vaccine	Drug: HRIG; A 20 IU/kg dose of BPL HRIG will be given on Day 0 via IM injection.; Biological: RabAvert; A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.; Other Names: active rabies vaccine
Active Comparator: Comparator HyperRab + RabAvert; 20 IU/kg dose HRIG + active rabies vaccine	Biological: RabAvert; A 1.0 ml dose of active vaccine (2.5 IU/ml) will be given IM on 5 occasions: on Days 0, 3, 7, 14, and 28.; Other Names: active rabies vaccine; Drug: HyperRAB; A 20 IU/kg dose of Comparator HRIG will be given on Day 0 via IM injection.; Other Names: HRIG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects With Anti-rabies Antibody Titer of ≥0.5 IU/mL	Non-inferiority in terms of the proportion of subjects with anti-rabies antibody titer of ≥0.5 IU/mL after study drug administration using a non-inferiority margin of 10%.	Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of AUC0-7d	The AUC0-7d for BPL HRIG and vaccine versus comparator HRIG and vaccine using a non inferiority margin of 20%.	Day 0 to Day 7
RVNA Geometric Mean Titers at Days 3, 5, 7 and 14	Comparison of the geometric mean titers (GMTs) for antirabies antibody titer after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine. The median peak RVNA titer occurred at Day 14, which is reflected in the analysis. The RVNA titer to peak geometric mean is analyzed using a repeated measures analysis. The inferential test compares RVNA values between BPL HRIG and HyperRab in a single analysis across all visits at or below the visit at which peak titer is observed. The geometric mean values presented represent a mean across all visits from baseline through and including Day 14.	Days 3, 5, 7 and 14
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ 0.5 IU/mL by Visit	The proportion of subjects reaching antirabies antibody titer of ≥ 0.5 IU/mL after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine.	Days 3, 5, 7, 14, 28, 49, and 140
Proportion of Subjects Reaching Antirabies Antibody Titer of ≥ LLOQ of the Assay by Visit	The proportion of subjects reaching antirabies antibody titer of ≥ LLOQ of the assay at each visit after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine.	Days 3, 5, 7, 14, 28, 49, and 140
RVNA Geometric Mean Titers at Days 14, 28, 49 and 140	Comparison of the GMTs for antirabies antibody titer after administration of BPL HRIG and vaccine versus comparator HRIG and vaccine to assess the inhibitory effects of BPL HRIG on active immunization relative to that of the comparator HRIG.	Days 14, 28, 49 and 140

Collaborators and Investigators

• Sponsor: Bio Products Laboratory
• Investigators: Study Director: Elizabeth Holmes, MD, Bio Products Laboratory

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2017
• Primary Completion (Actual): March 2, 2018
• Study Completion (Actual): July 13, 2018

Study Registration Dates

• First Submitted: August 22, 2017
• First Submitted That Met QC Criteria: August 24, 2017
• First Posted (Actual): August 29, 2017

Study Record Updates

• Last Update Posted (Actual): February 25, 2020
• Last Update Submitted That Met QC Criteria: February 12, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Mononegavirales Infections; Rhabdoviridae Infections; Rabies; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: RIG01

Drug and device information, study documents

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