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Background: ZyCoV-D is a DNA vaccine candidate, which comprises a plasmid DNA carrying spike-S gene of SARS-CoV-2 virus along with gene coding for signal peptide. The spike(S) region includes the receptor-binding domain (RBD), which binds to the human angiotensin converting Enzyme (ACE)-2 receptor and mediates the entry of virus inside the cell. Methods: We conducted a single-center, open-label, non-randomized, Phase 1 trial in India between July 2020 and October 2020. Healthy adults aged between 18 and 55 years were sequentially enrolled and allocated to one of four treatment arms in a dose escalation manner. Three doses of vaccine were administered 28 days apart and each subject was followed up for 28 days post third dose to evaluate safety and immunogenicity. Findings: Out of 126 individuals screened for eligibility. Forty-eight subjects (mean age 34¢9 years) were enrolled and vaccinated in the Phase 1 study Overall, 12/48 (25%) subjects reported at least one AE (i.e. combined solicited and unsolicited) during the study. There were no deaths or serious adverse events reported in Phase 1 of the study. The proportion of subjects who seroconverted based on IgG titers on day 84 was 4/11 (36¢36%), 4/12 (33¢33%), 10/10 (100¢00%) and 8/10 (80¢00%) in the treatment Arm 1 (1 mg: Needle), Arm 2 (1 mg: NFIS), Arm 3 (2 mg: Needle) and Arm 4 (2 mg: NFIS), respectively. Interpretation: ZyCoV-D vaccine is found to be safe, well-tolerated and immunogenic in the Phase 1 trial. Our findings suggest that the DNA vaccine warrants further investigation.

Background: Desidustat (ZYAN1) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that stimulates erythropoiesis. Stabilizing HIF via PHI is developing as a new therapeutic approach to treat anemia secondary to chronic kidney disease (CKD). This trial evaluated the safety, tolerability, and efficacy of Desidustat in adult CKD patients with anemia, who were not on dialysis. Methods: This was a Phase 2, randomized, double-blind, 6-week, placebo-controlled, dose-ranging, safety and efficacy study. A total of 117 eligible patients were randomized to 4 arms: 100, 150, 200 mg, or placebo. The investigational product was administered every alternate day for 6 weeks in fasting conditions. The primary endpoint was change in hemoglobin (Hb) from baseline to week 6. Results: Baseline demographics were well balanced among all the treatment arms. In the modified intent-to-treat (mITT) population, a mean Hb increase of 1.57, 2.22, and 2.92 g/dL in Desidustat 100, 150, and 200 mg arms, respectively, was observed post 6 weeks treatment. The responder rate (≥1 g/dL increase) was 66% in 100 mg, 75% in 150 mg, and 83% in 200 mg treatment arms, in the mITT population. Eighteen patients had at least one treatment emergent adverse event (TEAE), and 5 patients reported at least one drug-related mild TEAE. No death or serious adverse event was reported during the trial. Conclusion: There was dose-related increase in Hb across all doses compared to placebo in mITT and per-protocol populations. Desidustat also increased pharmacokinetic parameters Cmax and AUC in dose-related manner. There was no significant change in vital signs, electrocardiographic parameters, or safety laboratory values. Clinical Trial Registration Number CTRI/2017/05/008534 (registered on May 11, 2017).

Objective To evaluate the efficacy and safety of pegylated interferon alfa-2b (PEG IFN-α2b) along with the standard of care (SOC) in subjects with moderate COVID-19. Methods In this phase 2, randomized, open-label study, adult subjects aged >18 years with RT-PCR confirmed COVID-19 with moderate symptoms were randomized in a 1:1 to receive PEG IFN-α2b plus SOC, or SOC alone. The primary endpoint was improvement in clinical status on day 15, measured by WHO 7-point ordinal scale. Results Total 40 subjects were randomized to PEG IFN-α2b plus SOC (n = 20) and SOC (n = 20). Overall, 19 (95.00%) subjects in PEG IFN-α2b plus SOC had achieved clinical improvement on day 15 compared to 13 (68.42%) subjects in SOC (p < 0.05). Overall, 80% and 95% of subjects in the PEG IFN-α2b plus SOC group had a negative RT-PCR result on day 7 and day 14, respectively as compared to 63% and 68% in the SOC group. Adverse events (AEs) were reported for 11 subjects in the PEG IFN-α2b plus SOC group and 8 subjects in the SOC group. All reported AEs were mild. Conclusion The significant improvement in clinical status on day 15 is likely due to faster viral reduction compared to SOC with the PEG IFN-α2b treated moderate COVID-19 subjects showing a difference as early as day 7 and becoming significant by day 14.

Background and ObjectivesDyslipidaemia is a major cardiovascular risk factor associated with type 2 diabetes mellitus. Saroglitazar (ZYH1) is a novel peroxisome proliferator-activated receptor (PPAR) agonist with predominant PPARα and moderate PPARγ activity. It has been developed for the treatment of dyslipidaemia and has favourable effects on glycaemic parameters in type 2 diabetes mellitus. The objective of this phase 1 study was to evaluate the pharmacokinetics, safety and tolerability of saroglitazar in healthy human subjects.MethodsThis was a randomized, double-blind, placebo-controlled, single-centre, phase I study in healthy human volunteers, and was performed in two parts; part I evaluated single ascending oral doses of saroglitazar (0.125, 0.25, 0.5, 1, 2, 4, 8, 16, 32, 64 and 128 mg) in healthy subjects, and part II measured the effects of food and sex on the pharmacokinetics of 1 mg saroglitazar, the human equivalent efficacy dose derived from pre-clinical studies. A total of 96 subjects were enrolled in the study, which included 88 healthy male subjects in part I and 16 healthy subjects (8 males from part I of the study and 8 females) in part II.ResultsSaroglitazar was rapidly and well absorbed across all doses in the single-dose pharmacokinetic study, with a median time to the peak plasma concentration (tmax) of less than 1 h (range 0.63–1 h) under fasting conditions across the doses studied. The maximum plasma concentration ranged from 3.98 to 7,461 ng/mL across the dose range. The area under the plasma concentration–time curve increased in a dose-related manner. The average terminal half-life of saroglitazar was 5.6 h. Saroglitazar was not eliminated via the renal route. There was no effect of sex on the pharmacokinetics of saroglitazar, except for the terminal half-life, which was significantly shorter in females than in males. Food had a small effect on the pharmacokinetics; however, it was not consistent in males and females. Single oral doses of saroglitazar up to 128 mg were well tolerated. No serious adverse events were reported. Adverse events were generally mild and moderate in nature. Saroglitazar did not show any clinically relevant findings in clinical laboratory investigations, physical examinations, vital signs and electrocardiograms.ConclusionThe highest dose of saroglitazar evaluated in this study was 128 mg, several times the estimated therapeutic doses (1–4 mg). The pharmacokinetics of saroglitazar support a once daily dosage schedule. Saroglitazar was found to be safe and well tolerated in this study.