These four phase 3 trials offer encouraging results

The number of studies recorded at ClinicalTrials.gov has ballooned in recent years. In 2021, 52,536 studies were registered compared with 46,718 in 2020. Moreover, from January 1 through January 20, 2022, 262 studies were registered.

Of all the phases of studies, phase 3 trials perhaps have the most consumer relevance. The FDA uses phase 3 results to determine safety and efficacy of the agent under consideration. It behooves any clinician to monitor the results of important Phase 3 trials. If they receive FDA approval, these new agents could then make their way into patients’ medication histories, improving or saving lives.

Weight loss

The ability of antidiabetic agents to induce weight loss has been a hot topic as of late. In a 2022 JAMA study, researchers examined the effect of once-weekly subcutaneous semaglutide (2.4 mg), compared with once-daily subcutaneous liraglutide (3.0 mg) on weight loss. These agents were given in addition to lifestyle counseling in 338 participants, who were overweight or obese but without diabetes.

The researchers found that average body weight dropped by 15.8% with semaglutide compared with 6.4% with liraglutide from baseline to 68 weeks, which was statistically significant.

To date, this phase 3 trial is the first to compare glucagon-like peptide-1 analogues in terms of weight management. 

C. Difficile

Clostridium difficile infection is one of the most concerning diagnoses in medicine. To date, no treatments address the ability of this infection to disrupt the microbiome and facilitate C. difficile spore germination into toxin-producing bacteria. 

Results from a recent phase 3 trial published in NEJM assessed the efficacy of SER-109, which is an investigational microbiome agent made of purified Firmicutes spores used in the treatment of recurrent C. difficile infection. The investigators compared the experimental drug with placebo after standard-of-care antibiotic treatment. The primary outcome was a decrease in the recurrence of C. difficile infection up to 8 weeks after treatment.

The researchers found that in 182 patients, recurrence of C. difficile infection was 12% in the SER-109 group compared with 40% in the placebo group. Moreover, the experimental drug was just as safe as the placebo.

New COVID-19 vaccine

As COVID-19 evolves, its evolution affects vaccine efficacy, necessitating careful monitoring. In a first, researchers proved the efficacy of BBV152, a whole virion inactivated SARS-CoV-2 vaccine engineered with a toll-like receptor 7/8 agonist molecule, against the delta variant. The delta variant is one of the most common variants in the US and may be twice as contagious as other variants, with infection more severe.

In phase 1 and 2 studies, BBV152 has proven safe, immunogenic, and capable of triggering T-cell memory response. In a randomized, placebo-controlled, phase 3 trial published in the Lancet, researchers demonstrated that the vaccine was 65.2% effective against the delta variant, with no unexpected safety concerns.

Taken together, the safety, immunogenicity, and efficacy data regarding this vaccine could bode well for regulatory submissions of the virus, as well emergency use ordinances, according to the authors. 

“With the inclusion of vaccine vial monitors (category type 7), storage at 2–8°C, and a 28-day open-vial policy (limiting open-vial vaccine wastage by an estimated 10–25% on the basis of other multidose vaccines), the established efficacy of BBV152 against symptomatic infection could be crucial in further mitigating the COVID-19 pandemic,” the authors wrote.

Insomnia

Those with insomnia experience not only nighttime stress but also daytime impairment. Dual orexin receptor antagonists have demonstrated efficacy in treating some—but not all—symptoms of insomnia. In the current phase 3 study, researchers assessed the safety and efficacy of daridorexant, a novel orexin receptor antagonist, on nighttime and daytime symptoms of insomnia.

In a dyad of multicenter, randomized, double-blind, placebo-controlled phase 3 trials published in Lancet Neurology, researchers randomly assigned participants to daridorexant 50 mg, 25 mg, or placebo (study 1) or daridorexant 25 mg, 10 mg, or placebo (study 2) every night for 3 months. The researchers found that daridorexant 25 mg and 50 mg enhanced sleep outcomes, with daridorexant 50 mg improving daytime functioning in those with insomnia. In all groups, the treatments were safe, with nasopharyngitis and headache the most common adverse events. 

Sources

1. Ella R. Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial. The Lancet.

2. Feuerstadt P. SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection. NEJM.

3. Mignot E. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. Lancet Neurology.

4. Rubino DM. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes. JAMA.

5. Trends, charts, and maps. ClinicalTrials.gov.