A Clinical Trial to Evaluate the Safety and Immunogenicity of rVSV∆G-LASV-GPC Vaccine in Adults in Good General Heath

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

A Phase 1 Randomized, Double-blinded, Placebo-controlled, Dose-escalation Clinical Trial to Evaluate the Safety and Immunogenicity of rVSV∆G-LASV-GPC Vaccine in Adults in Good General Health

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: International AIDS Vaccine Initiative
• Collaborators: Brigham and Women's Hospital; East-West Medical Research Institute; George Washington University; Redemption Hospital
• Treatments: Vaccines

Criteria

Inclusion Criteria

1. Adults in good general health as assessed by medical history, physical examination, and laboratory tests

2. At least 18 years of age on the day of screening and has not reached his/her 51st birthday on the day of vaccination

3. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study

4. In the opinion of the Principal Investigator (PI) or designee and based on Assessment of Informed Consent Understanding results, has understood the information provided and potential impact and/or risks linked to administration and participation in the trial; written informed consent will be obtained from the participant before any study-related procedures are performed

5. Willing to undergo HIV testing, risk reduction counselling, and receive HIV test results

6. All WOCBP engaging in sexual activity that could lead to pregnancy must commit to use an effective method of contraception from at least 2 weeks before and continue until 4 months following receipt of vaccine/placebo, including at least one of the following. Study sites will choose which methods are most appropriate for their population and this will be specified in the Informed Consent Document (ICD):

• Condoms (male or female) with or without spermicide

• Diaphragm or cervical cap with spermicide

• Intrauterine device

• Long acting hormonal contraception, including contraceptive implant or injectable

• Oral contraceptive

• Successful vasectomy in the male partner (considered successful if a woman reports that a male partner has (1) documentation of azoospermia by microscopy (≤1 year ago), or (2) a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity post-vasectomy)

• Not be of reproductive potential, such as having undergone hysterectomy, bilateral oophorectomy, or tubal ligation, postmenopausal (>45 years of age with amenorrhea for at least 2 years, or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone [FSH] level ≥40 IU/L): no additional contraception required

• A site may require more stringent contraceptive practices if they believe it is appropriate

7. All sexually active participants must consistently use male or female condoms with all sexual partners for 4 months following IP administration

8. All participants who are not heterosexually active at screening, must agree to utilize an effective method of contraception if they become heterosexually active, as outlined above

9. All women must be willing to undergo a pregnancy test at time points indicated in the Schedule of Activities (SOA) unless not of reproductive potential

10. Willing to forgo donation of blood or any other tissues from screening onward throughout the course of the study

Exclusion Criteria

1. Confirmed HIV-1 or HIV-2 infection

2. Any clinically relevant abnormality on history or examination including history of immunodeficiency or autoimmune disease; use of corticosteroids, immunosuppressive, anticancer, or other medications considered significant by the Investigator within the previous 6 months. The following exceptions are permitted and will not exclude study participation: use of corticosteroid nasal spray for rhinitis, topical corticosteroids for an acute uncomplicated dermatitis; or a short course (duration of 10 days or less, or a single injection) of corticosteroid for a non-chronic condition (based on Investigator clinical judgment) at least 2 weeks prior to enrollment in this study

3. Any clinically significant chronic medical condition that, in the opinion of the Investigator, makes the participant unsuitable for participation in the study

4. Pregnant or lactating

5. Bleeding disorder that was diagnosed by a physician (eg, factor deficiency, coagulopathy, or platelet disorder that requires special precautions.) Note: A participant who states that he or she has easy bruising or bleeding but does not have a formal diagnosis and has intramuscular (IM) injections and blood draws without any adverse experience, is eligible.

6. Infectious disease: chronic active hepatitis B infection (HBsAg-positive), current hepatitis C infection (for Africa site - HCV Ab positive; for US sites - HCV Ab positive and HCV RNA positive), active syphilis (positive screening and confirmatory tests, and untreated), positive viral detection test for SARS-CoV2 (test at screening for COVID-19 if clinically indicated)

7. History of splenectomy

8. Any of the following abnormal laboratory parameters listed below:

Hematology

• Absolute Neutrophil Count (ANC): ≤1,000/mm3

• Absolute Lymphocyte Count (ALC): ≤650/mm3

• Hemoglobin (Liberia participants): <9.5 g/dl in females; <11.0 g/dl in males

• Hemoglobin (US participants): <10.5 g/dl in females; <11.0 g/dl in males

• Platelets (Liberia participants): <100,000 cells/mm3

• Platelets (US participants): <125,000 cells/mm3

Chemistry

• Creatinine >1.1 x upper limit of normal (ULN)

• ALT >1.25 x ULN

• AST >1.25 x ULN

Urinalysis

• Clinically significant abnormal dipstick confirmed by repeat dipstick on new specimen or by microscopy

• Protein = 1+ or more

• Blood = 2+ or more (not due to menses)

9. Receipt of live attenuated influenza vaccine within the previous 14 days, any other live attenuated vaccine within the previous 30 days or planned receipt within 30 days after vaccination with IP; or receipt of non-live attenuated vaccine within the previous 14 days or planned receipt within 14 days after vaccination with IP, including COVID-19 vaccines.

10. Prior receipt of another investigational Lassa vaccine candidate

Note: receipt of placebo in a previous LF vaccine trial will not exclude a participant from participation if documentation is available and the Medical Monitor gives approval.

11. Prior receipt of VSV-vectored vaccine (e.g. VSV-ZEBOV and VSV-HIV) Note: receipt of placebo in a previous VSV-ZEBOV or VSV-HIVvaccine trial will not exclude a participant from participation if documentation is available and the Medical Monitor gives approval.

12. Receipt of blood transfusion or blood-derived products within the previous 3 months

13. Prior exposure to LASV as documented by history (all groups). For participants enrolled in an endemic area, NP antibody test will be performed. If positive results are available prior to enrollment, participant will be excluded. If positive results are obtained after enrollment, participant will be followed per protocol, but data will be analyzed separately.

14. Participation in another clinical trial currently, within the previous 3 months, or expected participation during this study.

Note: Concurrent participation in an observational study not requiring any blood or tissue sample collection is not an exclusion.

15. History of severe local or systemic reactogenicity to any vaccine (eg, anaphylaxis, respiratory difficulties, angioedema, injection site necrosis, or ulceration)

16. Psychiatric condition or substance abuse that compromises safety of the participant and precludes compliance with the protocol. Specifically excluded are persons with psychoses in the last 3 years prior to screening, ongoing risk for suicide, or history of suicide attempt or gesture in the last 3 years prior to screening

17. Seizure disorder: A participant who has had a seizure in the last 3 years prior to screening is excluded. (Not excluded: a participant with a history of seizures who has neither required medications nor had a seizure in the last 3 years)

18. A history of malignancy in the past 5 years (prior to screening) or ongoing malignancy. (A history of a completely excised malignancy that is considered cured is not an exclusion)

19. Active, serious infections requiring parenteral antibiotic, antiviral or antifungal therapy within 30 days prior to enrollment

20. Body mass index (BMI) ≥35

21. Mild or greater hearing loss defined as ≥26dB loss in the better hearing ear

22. Otorrhea within the past 90 days, sudden or rapid hearing loss within the past 90 days, acute or chronic dizziness, otalgia. (External ear otalgia is not an exclusion)

23. History of chronic or acute severe neurologic condition (e.g., diagnosis of Guillain-Barré syndrome, epilepsy, Bell's palsy, meningitis or disease with any focal neurologic deficits).

24. History of any condition associated with sensorineural hearing loss that, in the opinion of the investigator, may interfere with the detection of changes in hearing during the study (e.g. occupational noise exposure, congenital infection, Meniere's disease, acoustic neuroma).

25. Clinically relevant abnormal otoscopy, that in the opinion of the investigator, may interfere with the detection of changes in hearing

26. For study participants in the dose-escalation phase of the study:

Current or planned occupational (medical care, child care) or household contact (residing in the same household) from screening through 3 months after IP administration with any individual at increased risk from exposure to a live viral vaccine including infants less than 1 year of age, adults over 65 years of age, or immunocompromised individuals

27. If, in the opinion of the PI, it is not in the best interest of the participant to participate in the trial