A First-in-human Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Stabilized CH505 TF chTrimer in Healthy, HIV-uninfected Adult Participants.
A First-in-human Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Stabilized CH505 TF chTrimer in Healthy, HIV-uninfected Adult Participants.
This is an open-label Phase 1 study to examine the safety and immunogenicity of the CH505 TF chTrimer vaccine with 3M-052-AF +/- Alum adjuvant in healthy adults. The primary hypothesis is that the CH505 TF chTrimer will expand CH103-like B-cell precursors.
HVTN 300 Part A examined the safety and immunogenicity of the CH505TF chTrimer with 5 mcg 3M-052-AF + 500 mcg Alum.
HVTN 300 Part B was added to this protocol with a goal of assessing the optimal dosing and combination of 3M-052-AF and Alum adjuvant, that can potentially lead to improved neutralizing antibody activity and decreased reactogenicity, compared to Part A. Three groups were added to Part B (Group 2: 3 mcg 3M-052-AF without Alum, Group 3: 3 mcg 3M-052 with Alum, and Group 4: 5 mcg 3M-052-AF without Alum).
HVTN 300 Part B is being added to this protocol with a goal of assessing the optimal dosing and combination of 3M-052-AF and Alum adjuvant, that can potentially lead to improved neutralizing antibody activity and decreased reactogenicity, compared to Part A. Three groups have been added to Part B (Group 2: 3 mcg 3M-052-AF without Alum, Group 3: 3 mcg 3M-052 with Alum, and Group 4: 5 mcg 3M-052-AF without Alum).
The primary hypothesis is that the CH505 TF chTrimer vaccine will expand B cell precursor lineages capable of ultimately producing autologous and heterologous Tier 2 broadly neutralizing antibodies (bnAbs). Participants receive CH505 TF chTrimer plus 3M-052-AF (at either a 3 mcg dose or a 5 mcg dose), with or without Alum, via two intramuscular injections administered five times throughout the study. Participants are evaluated for safety and immune responses through blood collection at specified timepoints throughout the study. Each participant has up to 18 months of scheduled clinic visits and a follow-up safety assessment 12 months after their final vaccination.
Inclusion Criteria:
Able and willing to complete the informed consent process, including an Assessment of Understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly.
18-55 years old, inclusive, on day of enrollment.
Available for clinic follow-up through the last clinic visit, willing to undergo lymph node fine needle aspiration and leukapheresis, and willing to be contacted 12 months after the last vaccine administration.
Agrees not to enroll in another study of an investigational agent during participation in the trial.
In good general health according to the clinical judgement of the site investigator.
Physical examination and laboratory results without clinically significant findings that would interfere with assessment of safety or reactogenicity in the clinical judgement of the site investigator.
Assessed as low risk for HIV acquisition per low risk guidelines (see protocol for more information), agrees to discuss HIV infection risks, agrees to risk reduction counseling, and agrees to avoid behavior associated with high risk of HIV exposure through the final study visit. Low risk may include persons stably taking PrEP (pre- exposure prophylaxis) as prescribed for 6 months or longer.
Hemoglobin >12.5 mg/dL to 18 mg/dL
White blood cell (WBC) count > 3,500/mm³
Platelets ≥125,000 /mm³
Alanine aminotransferase (ALT) < 2.5 x ULN based on the institutional normal range
Serum creatinine ≤1.1 x ULN based on the institutional normal range
Blood pressure in the range of 90 to < 160 mmHg systolic and 50 to < 100 mmHg diastolic.
Negative results for HIV infection by an FDA-approved enzyme immunoassay (EIA) or chemiluminescent microparticle immunoassay (CMIA).
Negative for anti-Hepatitis C antibodies (anti-HCV) or negative HCV nucleic acid test (NAT) if anti-HCV antibodies are detected.
Negative for Hepatitis B surface antigen.
For a volunteer capable of becoming pregnant:
Exclusion Criteria:
Volunteer who is breast-feeding or pregnant.
Previous or current recipient of an investigational HIV vaccine (previous placebo recipients are not excluded).
Systemic glucocorticoid use equal to or greater than prednisone10 mg/day within 3 months prior to enrollment, congenital or acquired immunodeficiency or other systemic medication use likely to impair immune response to vaccine in the opinion of the site investigator.
Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires PSRT approval.
Receipt of any live attenuated vaccine within 4 weeks prior to enrollment.
Receipt of any vaccines that are not live attenuated within 14 days prior to enrollment; replication incompetent vaccines such as the Jynneos vaccine for the prevention of monkeypox disease are not considered to be live vaccines.
ACAM2000 vaccine for Monkeypox received within 30 days prior to enrollment or receipt of study product, or if ACAM2000 received greater than 30 days prior to enrollment or receipt of study product, vaccination scab still present; or planned administration within 30 days after enrollment or receipt of study product.
Initiation of antigen-based immunotherapy for allergies within the previous year (stable immunotherapy is not exclusionary); inclusion of participants who initiated immunotherapy within the previous year requires PSRT approval.
Receipt of investigational research agents with a half-life of 7 or fewer days within 4 weeks prior to enrollment. If a potential participant has received investigational agents with a half-life greater than 7 days (or unknown half- life) within the past year, PSRT approval is required for enrollment.
Serious reactions to vaccines that preclude receipt of study injections as determined by the principal investigator or designee. History of serious reaction (eg. hypersensitivity, anaphylaxis) to any vaccine or any component of the study vaccine, including imidazoquinolone (eg, imiquimod).
Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
Idiopathic urticaria within the past year.
Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions).
Seizure disorder; febrile seizures as a child or seizures secondary to alcohol withdrawal more than 5 years ago are not exclusionary.
Asplenia or functional asplenia.
Active duty and reserve US military personnel.
Any other chronic or clinically significant condition that in the clinical judgement of the investigator would jeopardize the safety or rights of the study participant, including, but not limited to: clinically significant forms of drug or alcohol abuse, serious psychiatric disorders, or cancer that, in the clinical judgement of the site investigator, has a potential for recurrence (excluding basal cell carcinoma).
Asthma is excluded if the participant has ANY of the following:
A participant with a history of an immune-mediated disease, either active or remote. Specific examples are listed in Appendix F (AESI index). Not exclusionary:
History of allergy to local anesthetic (Novocaine, Lidocaine).
Investigator concern for difficulty with venous access based upon clinical history and physical examination. For example, history of IV drug abuse or substantial difficulty with previous blood draws.