Janssen publishes interim results of the Phase III study of its vaccine candidate against SARS-CoV.2
02.02.2021 11:36
Janssen Pharmaceutical Companies of Johnson & Johnson announced topline efficacy and safety data from its Phase 3 clinical trial ENSEMBLE on January 29, 2021. The data show that Janssen Pharmaceutical Companies' single-dose COVID-19 vaccine candidate met its primary and key secondary endpoints. The topline safety and efficacy data are based on 43,783 participants, of whom 468 experienced symptomatic cases of COVID-19.
The Phase 3 ENSEMBLE trial investigated the efficacy and safety of Janssen's vaccine candidate in protecting against moderate to severe COVID-19 infection 14 and 28 days after vaccination. The study included participants from various regions, including those infected with a novel variant of the virus. Overall, Janssen's COVID-19 vaccine candidate demonstrated 66 % of protection against moderate to severe COVID-19 infection after 28 days. The onset of protection was observed as early as day 14. At 28 days post-vaccination, the level of protection against moderate to severe COVID-19 infection was 72 % in the US, 66 % in Latin America, and 57 % in South Africa.
Protection against Covid-19-related hospitalizations and deaths
The vaccine candidate was 85% effective in preventing severe COVID-19 infections in all regions studied, with efficacy at 28 days post-vaccination in all adults aged 18 years and older. Efficacy against severe COVID-19 infections increased over time, with no cases reported in vaccinated participants after day 49.
Janssen's COVID-19 vaccine candidate demonstrated complete protection against COVID-19-related hospitalizations and deaths 28 days after vaccination. The vaccine had a significant effect on COVID-19 cases requiring medical intervention (hospitalization, ICU admission, mechanical ventilation, extracorporeal membrane oxygenation (ECMO)). No cases requiring such medical interventions were reported among study participants who received the Janssen COVID-19 vaccine candidate 28 days after vaccination.
„Achieving these results after a single vaccination with our COVID-19 vaccine candidate is very positive, especially considering the high level of protection against severe cases. Significantly reducing human suffering and the burden on healthcare systems is our primary goal. An effective and safe vaccine is essential in the fight against the pandemic,“ says Dr. Christoph Bug, Medical Director and member of the Management Board of Janssen Germany.
In the study, severe COVID-19 was defined by, among other things, laboratory-confirmed SARS-CoV-2 and one or more of the following: signs of severe systemic illness, admission to an intensive care unit, respiratory failure, shock, organ failure, or death. Moderate COVID-19 was defined as laboratory-confirmed SARS-CoV-2 and one or more of the following: signs of pneumonia, deep vein thrombosis, shortness of breath or abnormal blood oxygen saturation above 93 TpF, abnormal respiratory rate (≥20); or two or more systemic symptoms indicative of COVID-19.
Protection was generally consistent across all ethnic groups, age groups, including adults over 60 years of age (N= 13,610), and across all variants and regions studied, including South Africa, where almost all cases of Covid-19 (95%) were due to infection with a SARS-CoV-2 variant from the B.1351 lineage.
Study provides clinical data on several newly emerging virus mutations
The results of the ENSEMBLE study include efficacy against emerging strains of the coronavirus, including some highly infectious variants present in the US, Latin America, and South Africa. The Phase 3 ENSEMBLE study is being conducted at the height of the COVID-19 pandemic in eight countries and three regions, at a time when the spread of the disease was accelerating globally, leading to increased human exposure to the virus.
The participants in the Phase 3 ENSEMBLE trial will be followed for up to two years to assess safety and efficacy. Therefore, these data may be updated based on ongoing analyses. The complete available dataset will be submitted to a peer-reviewed journal in the coming weeks.
Phase 3 ENSEMBLE study safety data
The analysis included a concurrent review of available safety data from the Phase 3 ENSEMBLE trial by the Data and Safety Monitoring Board (DSMB), an independent expert group, which reported no significant safety concerns regarding the vaccine. A review of adverse events indicated that a single dose of Janssen's COVID-19 vaccine candidate was generally well tolerated.
The safety profile was consistent with that of other vaccine candidates using Janssen's AdVac® technology and has been observed in more than 200,000 people to date. The overall fever rate was 91 TP3T and the fever grade 3 rate was 0.21 TP3T. Overall, the reported serious adverse events (SAEs) were higher in the placebo group than in the active vaccine candidate group. No cases of anaphylaxis were observed.
Access and distribution
Janssen will make its vaccine candidate available on a non-profit basis during the pandemic, pending approval. Furthermore, the Janssen vaccine candidate is compatible with standard vaccine distribution channels. If approved, Janssen's single-dose vaccine candidate is estimated to remain stable for two years at -20°C, including at least three months at temperatures between 2°C and 8°C. The company will ship the vaccine using the same cold chain technologies it currently employs to transport other innovative medicines.
Janssen intends to apply for an Emergency Use Authorization (EUA) in the US in early February and expects the vaccine to be ready for delivery once approved. Further production details will be released as regulatory approvals are received and contracts are finalized. Janssen currently anticipates fulfilling its 2021 supply agreements, including those signed with governments and global organizations.
Phase 3 ENSEMBLE study design
The Phase 3 ENSEMBLE trial is a randomized, double-blind, placebo-controlled clinical trial investigating the safety and efficacy of a single-dose vaccine compared to placebo in adults aged 18 years and older. The ENSEMBLE trial is designed to assess the safety and efficacy of the Janssen vaccine candidate in protecting against moderate to severe COVID-19 infection, with efficacy assessments from day 14 and day 28 as co-primary endpoints.
Phase 3 ENSEMBLE study: Demographic data
The study, conducted in eight countries across three continents, encompasses a diverse and broad population, including 341 participants aged 60 and older (N=14,672). Specifically, 441 participants aged 60 and older (N=19,302) were enrolled in the USA, 411 participants aged 60 and older (N=17,905) in Central and South America (Argentina, Brazil, Chile, Colombia, Mexico, Peru), and 151 participants aged 60 and older (N=6,576) in South Africa.
Forty-five percent of the participants are female, 551 are male. Of the participants worldwide, 591 are White/Caucasian, 451 are Hispanic and/or Latino, 191 are Black/African, 91 are Native American, and 31 are Asian. In the USA, 74 are White/Caucasian, 15 are Hispanic and/or Latino, 13 are Black/African, 6 are Asian, and 1 is Native American.
41 percent of the study participants had comorbidities associated with an increased risk of progression of severe Covid-19 infection (total 41 %, obesity (28.5 %), type 2 diabetes (7.3 %), hypertension (10.3 %), HIV (2.8 %); other immunocompromised participants were also included in the study.