Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as AERAS-404, H4
H4:IC31 · 3 trials · 1 indication
Number of unsolicited and solicited adverse events recorded post vaccination. Unsolicited adverse events: 28 days post each vaccination Solicited adverse events: 7 days post each vaccination (with diary cards used for 7 days after each vaccination for Safety and Immunogenicity Cohort only) Solicited and unsolicited injection site reaction adverse events: BCG Group - 84 days post vaccination; H4:IC31/Placebo Groups - 28 days post each vaccination Serious adverse events, adverse events of special interest, and SUSARs: Entire study period, with a minimum of 6 months following the last dose of study vaccine
Rates of conversion to Mtb-positive measured by QuantiFERON-TB Gold In-tube (QFT-GIT) assay. The primary evaluation of Mtb infection was QFT-GIT conversion from a negative to positive test, using the manufacturer's recommended threshold of ≥0.35 IU/mL, at any time point after Day 84 and through end of follow-up for the primary endpoint. All participants with primary QFT-GIT conversion were followed for an additional 6 months post-conversion to ascertain the sustained QFT-GIT conversion and QFT-GIT reversion endpoints. Participants with an initial QFT-GIT conversion at Month 6 or 12 were asked to return for a final QFT-GIT evaluation and assessment for TB signs and symptoms at least 24 months after their initial vaccination. * H4:IC31 compared to placebo * BCG revaccination compared to placebo
Includes injection site AEs and systemic AEs.
The number of solicited and unsolicited adverse events (AEs), including serious adverse events (SAEs), recorded post-vaccination for all participants.
Flow cytometry was used to examine TB Mb-specific CD4+ and CD8+ T-cell responses using the ICS assay. The antigens used to stimulate cells in this assay included peptide pools for the vaccine-matched proteins (Ag85B, ESAT-6, Rv2660c, and TB 10.4) as well as complex TB antigens (TB whole cell lysate \[TB WCL\], and BCG Pasteur strain.
| Arm | Type | Description |
|---|---|---|
| AERAS-404 (15 mcgH4/500 nmol IC31) | EXPERIMENTAL | 2 doses on Study Days 0 and 56 |
| Bacillus Calmette-Guérin (BCG) | ACTIVE_COMPARATOR | 1 Dose on Study Day 0 |
| Placebo | PLACEBO_COMPARATOR | 2 Doses on Study Days 0 and 56 |
| BCG SSI prime with Placebo | PLACEBO_COMPARATOR | All subjects received BCG Vaccine SSI, 2-8 x 10\^5 CFU (BCG) on Study Day -42. Placebo containing 0,8 mL sterile buffer consisting of 10 mmol Tris and 169 mmol NaCl aqueous solution was administered on Study Days 0, 56, and 231. |
| BCG SSI prime with Placebo and AERAS-404 | EXPERIMENTAL | All subjects received BCG Vaccine SSI, 2-8 x 10\^5 CFU (BCG) on Study Day -42. Placebo on Study Day 0 followed by AERAS-404 50/500 on Study Days 56 and 231. AERAS-404 50/500 was a fixed dose combination of H4 50 mcg and IC31 500 nmol (KLK equivalent). H4 and IC31 adjuvant were supplied as separate single-dose vials containing frozen product as follows: * H4 antigen: 500 mcg/mL (100 mcg/0.2 mL), in 10 mmol/L Tris-HCl, pH 8.3. * IC31 adjuvant: 1250 nmol/mL (1000 nmol/0.8 mL) KLK equivalent, in 10 mmol/L Tris-HCl and 169 mmol/L NaCl. |
| BCG SSI prime with AERAS-404 | EXPERIMENTAL | All subjects received BCG Vaccine SSI, 2-8 x 10\^5 CFU (BCG) on Study Day -42. AERAS-404 50/500 on Study Days 0, 56, and 231. AERAS-404 50/500 was a fixed dose combination of H4 50 mcg and IC31 500 nmol (KLK equivalent). H4 and IC31 adjuvant were supplied as separate single-dose vials containing frozen product as follows: * H4 antigen: 500 mcg/mL (100 mcg/0.2 mL), in 10 mmol/L Tris-HCl, pH 8.3. * IC31 adjuvant: 1250 nmol/mL (1000 nmol/0.8 mL) KLK equivalent, in 10 mmol/L Tris-HCl and 169 mmol/L NaCl. |
| Group 1 H4:IC31 | EXPERIMENTAL | 15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56. |
| Group 2 H56:IC31 | EXPERIMENTAL | 5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56. |
| Group 3 BCG (2-8 x 105 CFU) | ACTIVE_COMPARATOR | Administered IM as 0.1 mL in either deltoid muscle at Day 0. |
| Group 4 Control Sodium Chloride 0.9% | PLACEBO_COMPARATOR | Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56. |
| Name | Type | Description |
|---|---|---|
| AERAS-404 | BIOLOGICAL | The H4 antigen is a fusion protein created from two Mtb antigens: antigen Ag85B and TB10.4. Ag85B is also referred to as α-antigen and is a 30-kDa mycolyl transferase protein. TB10.4 is one of three members of the very similar ESAT-6 group of proteins found in Mtb culture supernatants. TB10.4 induces broad immune responses in T cells isolated from TB subjects compared to BCG-vaccinated donors and unvaccinated donors. IC31 is a combination of a leucine-rich peptide named KLK \& a synthetic oligonucleotide named ODN1a. The optimal molar ratio of KLK to ODN1a in mice is 25:1. AERAS-404 \& saline placebo trial arms will be double-blinded since BCG causes a recognizable local injection site reaction, the BCG revaccination trial arm will be unblinded. |
| Placebo | DRUG | Saline |
| Bacillus Calmette-Guérin (BCG) | BIOLOGICAL | BCG SSI Vaccine is registered in South Africa for prevention of TB in children and adults. BCG, an attenuated, live culture of the Bacillus Calmette-Guérin, was originally attenuated between 1906 and 1919 by serial passage of an M. bovis strain. The manufacturer Statens Serum Institut (SSI) in Copenhagen, Denmark derives this vaccine from the Danish BCG strain 1331. BCG SSI is supplied by the manufacturer in amber 10-dose vials containing 0.75 mg lyophilized SSI BCG. The BCG revaccination trial arm will be unblinded (open label). |
| BCG SSI | BIOLOGICAL | The dose volume administered for BCG was 0.1 mL, and the mode of administration was ID injection to the deltoid area. |
| H4:IC31 | BIOLOGICAL | H4 contains Mtb antigens Ag85B and TB10.4 |
| H56:IC31 | BIOLOGICAL | H56 contains Mtb antigens ESAT-6, and Rv2660c |
| BCG | BIOLOGICAL | - |
| Control Sodium Chloride 0.9% | BIOLOGICAL | - |
Inclusion Criteria: 1. Has completed the written informed consent and assent process 2. Is age ≥ 12 years and ≤ 17 years on Study Day 0 3. Agrees to stay in contact with the study site for the duration of the study, provide updated contact information 4. For female subjects: agrees to avoid pregnan...
Top 2 of 3 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| BioNTech SE Sponsored ADR | BNTX | 1 | PHASE1 | BNT164a1, BNT164b1 |
| GSK plc Sponsored ADR | GSK | 1 | PHASE1 | Ganfeborole |
H4:IC31 is an investigational vaccine candidate being studied for the prevention of tuberculosis. It is designed to be used in revaccination strategies, including in combination with BCG, to enhance immune responses against Mycobacterium tuberculosis. The Phase 1 trial NCT02378207 evaluated its safety and immunogenicity in healthy adolescents in South Africa.
H4:IC31 is being developed by Sanofi, a global pharmaceutical company traded on the New York Stock Exchange under the ticker SNY. Sanofi's involvement is part of its infectious disease portfolio, though specific partnership details are not provided. The vaccine candidate is in Phase 1 clinical development.
H4:IC31 is in Phase 1 clinical development. It has completed one Phase 1 trial, NCT02378207, which enrolled 84 healthy adolescents in South Africa. The trial was randomized, double-blind, and placebo-controlled, assessing safety and immunogenicity. There are currently no active trials for H4:IC31.
H4:IC31 has been evaluated in one completed Phase 1 clinical trial, NCT02378207, titled "Safety and Immunogenicity Study of BCG, H4:IC31, and H56:IC31 Revaccination in Healthy Adolescents." The trial enrolled 84 participants in South Africa and was randomized, double-blind, and placebo-controlled. No active trials are ongoing.
No, H4:IC31 is not FDA approved. It is an investigational vaccine candidate still in Phase 1 clinical development. The only completed trial, NCT02378207, was a Phase 1 study in healthy adolescents. Further clinical testing would be required before any potential regulatory approval.