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Phase 2 study expected to enroll 600 participants Finalizing protocol for Phase 3 study, expected to begin in July 2020 Moderna, Inc. , (Nasdaq: MRNA) a clinical stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines otday announced that the first participants in each age cohort have been dosed in the Company’s Phase 2 study of its mRNA vaccine candidate (mRNA-1273) against the novel coronavirus (SARS-CoV-2).

This Phase 2 study, being conducted by Moderna under its own Investigational New Drug (IND) application, will evaluate the safety, reactogenicity and immunogenicity of two vaccinations of mRNA-1273 given 28 days apart. The Company intends to enroll 600 healthy participants across two cohorts of adults ages 18-55 years (n=300) and older adults ages 55 years and above (n=300). Each participant will be assigned to receive placebo, a 50 μg or a 100 μg dose at both vaccinations. Participants will be followed through 12 months after the second vaccination. Given the 25 μg and 100 μg dose levels in the Phase 1 study showed neutralizing antibody titers at or above convalescent sera and were generally well tolerated, the Company has decided not to pursue the 250 μg dose level in the Phase 2 study. On May 6, the U.S. Food and Drug Administration (FDA) completed its review of the Company’s Investigational New Drug (IND) application for mRNA-1273 and on May 12, the FDA granted it Fast Track designation. On May 18, Moderna announced initial data from the Phase 1 study of mRNA-1273 led by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). The NIH will be submitting the Phase 1 data to a peer-reviewed clinical publication. Moderna anticipates collaborating with NIAID to implement the Phase 3 study. The dose for the Phase 3 study is expected to be between 25 µg and 100 µg and expects Phase 3 trial initiation in July, subject to finalization of the clinical trial protocol.

Funding from the Biomedical Advanced Research and Development Authority (BARDA), a division of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services (HHS), supported the planning for these studies and will also support the late-stage clinical development programs, as well as the scale-up of mRNA-1273 manufacturing both at the Company’s facilities and that of its strategic collaborator, Lonza Ltd. A summary of the company’s work to date on SARS-CoV-2 can be found here.

Summary: HIV can persist in the nervous system, even when the virus is suppressed. Even when the virus is suppressed, neurocognitive problems associated with the infection can persist.

Investigators from the University of North Carolina, the University of Pittsburgh, and Yale University studied participants enrolled in the AIDS Clinical Trials Group (ACTG) HIV Reservoirs Cohort Study. This primarily male group–aged 45 to 56–of long-term HIV survivors had infections controlled with ART for on average nine years. Researchers analyzed each participant’s CSF for HIV DNA and then compared these data to each participants’ results from standard neurocognitive evaluations. About half of participants had viral DNA in cells in the CSF, indicating the presence of latent virus, even though standard HIV RNA ‘viral load’ tests of the cell-free CSF fluid were positive in only 4% of participants. Investigators also found that 30% of individuals with persistent HIV DNA in the CSF experienced clinical neurocognitive impairment compared with 11% of individuals whose CSF did not contain viral DNA.

The new findings suggest that the presence of persistent HIV-infected cells in the central nervous system (CNS), despite long-term ART, may play a role in neurocognitive impairment. The authors note that the overall frequency of neurocognitive impairment in this group was relatively low and that the association does not confirm that HIV DNA causes HAND. Overall, the current study found that examining CSF cells revealed a higher-than-expected prevalence of persistent HIV in the CNS, which may be a significant obstacle to efforts to eradicate HIV from the body.

The study was published on July 15, 2019 in the J. Clinical Invest.:

https://doi.org/10.1172/JCI127413

The study’s small size and other weaknesses mean it does not offer a lot of helpful information in determining the possible utility of hydroxychloroquine, according to experts who reviewed the study. Results from the first controlled study of hydroxychloroquine for treating COVID-19 showed no significant difference in outcomes between those who received the drug and those who received usual care. Hydroxychloroquine is one of several existing drugs that scientists are hoping will show improved symptoms and recovery in clinical trials for in patients with COVID-19. However, the study’s small size and other weaknesses mean it does not offer a lot of helpful information in determining the possible utility of hydroxychloroquine, according to experts who reviewed the study. The study also tested only hydroxychloroquine alone, not with the antibiotic azithromycin. 

“The combination therapy of azithromycin and hydroxychloroquine was thought to be better over the monotherapy of hydroxychloroquine to control the mixed infection of virus and bacteria,” explained Sunit K. Singh, PhD, a professor of molecular immunology & virology and head of the molecular biology unit at Banaras Hindu University’s Institute of Medical Sciences in Varanasi, India. 

Hydroxychloroquine, known by the brand name Plaquenil, is currently used to treat lupus and rheumatoid arthritis. It is slightly different from chloroquine phosphate, another drug, currently used to treat malaria, which is under investigation for treating COVID-19. Both drugs have been in use for decades but carry risks as well. “During any outbreaks of epidemic and pandemic levels, there is hardly any time left for new drug development and clinical trials,” Dr. Singh said. Therefore clinicians will turn to trying existing drugs, known as “repurposing.”

Preprint (Chinese) of the study available at:

http://subject.med.wanfangdata.com.cn/UpLoad/Files/202003/43f8625d4dc74e42bbcf24795de1c77c.pdf