Effect of Raxibacumab on Immunogenicity of Anthrax Vaccine Adsorbed

NCT02339155 | Completed Phase 4 Results

• 1 other identifier: 201436
• Study Type: interventional
• Target: 573
• Locations: 1 country
• Sites: 3

Brief Summary

This study, as a post-marketing commitment to the Food and Drug Administration, is designed to detect the effect of raxibacumab on anthrax vaccine adsorbed (AVA) immunogenicity in a healthy volunteer population. This is a randomized, open-label, parallel group, two arm study to compare the immunogenicity of AVA at 4 weeks after the first AVA dose, when AVA is administered alone or concomitantly with raxibacumab. The study is planned to enroll approximately 30 to 534 subjects in up to 3 cohorts. The total duration of the study will be approximately 26 weeks. The dates reflect cohort 1.

Conditions

Infections, Bacterial

Keywords

Anthrax Vaccine Adsorbed; Raxibacumab; Immunogenicity

Outcome Measures

Primary Outcomes (1)

• Ratio of Geometric Mean Concentrations (GMC) of Anti-protective Antigen (PA) Antibody (Ab) at 4 Weeks (Day 29) After the First AVA Dose (Prior to the Third AVA Dose), Between the AVA Alone and the AVA With Raxibacumab Treatment Groups

  Ratio of the GMC of anti-PA Ab between AVA alone and the AVA with raxibacumab treatment group was assessed to compare the immunogenicity of AVA at 4 weeks after the first AVA dose (prior to the third AVA dose). Serum AVA derived anti-PA Ab concentrations were determined using an approved immunoassay. Per Protocol (PP) population was used in analysis which comprised of all analyzable participants (those who received at least the Week 0 \[Day 1\] and Week 2 \[Day 15\] AVA doses within the protocol specified visit window; receive the raxibacumab dose, if randomized to Treatment Group 2 and; completed the primary study endpoint assessment \[anti-PA Ab concentration at Week 4\]).

  Day 29

Secondary Outcomes (10)

• Ratio of GMC of Anti-PA Ab at Weeks 8 and 26 (Days 57 and 183) After the First AVA Dose, Between the AVA Alone and AVA With Raxibacumab Treatment Groups

  Days 57 and 183

• Percentage of Participants Who Seroconvert, at Weeks 4, 8, and 26 (Days 29, 57 and 183) After the First AVA Dose, Between the AVA Alone and the AVA With Raxibacumab Treatment Groups

  Days 29, 57 and 183

• Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (AE)

  Up to Day 183

• Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points

  Baseline and up to Day 183

• Change From Baseline in Heart Rate at Indicated Time Points

  Baseline and up to Day 183

Study Arms (2)

Anthrax Vaccine Adsorbed

EXPERIMENTAL

Subjects will be administered subcutaneous (SC) 0.5 mL AVA doses on Days 1, 15, and 29 (0, 2, and 4 weeks).

Biological: AVA

AVA + Raxibacumab

EXPERIMENTAL

Subjects will be administered SC 0.5 mL AVA doses on Days 1, 15, and 29 (0, 2, and 4 weeks), with the first AVA dose administered immediately after completion of a single intravenous (IV) infusion 40 milligram (mg)/kilogram (kg) raxibacumab dose. Subjects will be premedicated with 25-50 mg of diphenhydramine up to 1 hour prior to the raxibacumab infusion to reduce the risk of infusion reactions.

Biological: AVA; Biological: Raxibacumab; Drug: Diphenhydramine

Interventions

AVA BIOLOGICAL

Sterile, milky-white suspension with dosage level of 0.5 mL for SC administration

AVA + Raxibacumab; Anthrax Vaccine Adsorbed

Raxibacumab BIOLOGICAL

Sterile, liquid formulation with unit dose strength of 40 mg/ kg for IV administration

AVA + Raxibacumab

Diphenhydramine DRUG

Depending upon the labelling of the specific product chosen, 25 - 50 mg will be administered orally or IV

AVA + Raxibacumab

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination and laboratory tests
• Men and women between 18 to 65 years of age
• Willing and able to adhere to the procedures stated in the protocol.
• Female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum or urine human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies:
• Non-reproductive potential defined as:
• Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy Postmenopausal defined as 12 months of spontaneous amenorrhea. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment.
• Reproductive potential and agrees to follow one of the options listed in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP), from 30 days prior to the first dose of study medication and until after the last dose of study medication and completion of the follow-up visit at Day 183 (at least five terminal half-lives for raxibacumab).

You may not qualify if:

• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or non-investigational study vaccine/product (pharmaceutical product or device).
• Be a member of the military, a laboratory worker, first responder, health care worker, or otherwise be at higher risk of exposure to anthrax.
• History of regular alcohol consumption within 1 month of the study defined as:
• An average weekly intake of \>14 drinks for males or \>7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 milliliter \[mL\]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
• Female planning to become pregnant or planning to discontinue contraceptive precautions before the Day 183 study visit.
• Pregnant (confirmed by a serum or urine hCG test) or lactating female.
• Alanine aminotransferase (ALT) and bilirubin \>1.5 x upper limit of normal (ULN) (isolated bilirubin \>1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., malignancy, human immunodeficiency virus \[HIV\] infection) or immunosuppressive/cytotoxic therapy (e.g., medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders).
• Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test results at screening or within 3 months prior to first dose of study treatment.
• A positive pre-study drug/alcohol screen.
• A positive test for HIV antibody.
• History of sensitivity to any of the study medications, or components thereof (especially latex and aluminium) or a history of other known drug allergies that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates their participation.
• Have previously been vaccinated against PA.
• Have an anti-PA Ab concentration \>2 times the lower limit of quantitation at screening.

Sponsors & Collaborators

• Emergent BioSolutions: lead
• GlaxoSmithKline: collaborator

Study Sites (3)

GSK Investigational Site

Edgewater, Florida, 32132, United States

Location

GSK Investigational Site

Overland Park, Kansas, 66211, United States

Location

GSK Investigational Site

Knoxville, Tennessee, 37920, United States

Location

Related Publications (1)

• Skoura N, Wang-Jairaj J, Della Pasqua O, Chandrasekaran V, Billiard J, Yeakey A, Smith W, Steel H, Tan LK. Effect of raxibacumab on immunogenicity of Anthrax Vaccine Adsorbed: a phase 4, open-label, parallel-group, randomised non-inferiority study. Lancet Infect Dis. 2020 Aug;20(8):983-991. doi: 10.1016/S1473-3099(20)30069-4. Epub 2020 Apr 22.

  PMID: 32333847 DERIVED

MeSH Terms

Conditions

Bacterial Infections

Interventions

raxibacumab; Diphenhydramine

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• Paul-Andre deLame, MD

  Emergent BioSolutions Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2015
• First Posted: January 15, 2015
• Study Start: February 24, 2015
• Primary Completion: January 3, 2017
• Study Completion: June 6, 2017
• Last Updated: March 18, 2024
• Results First Posted: January 9, 2018

Record last verified: 2024-03

Locations

US (3)