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INTRODUCTION:Obesity is highly prevalent in India, creating an urgent need for effective management interventions. The study hypothesizes that synthetic semaglutide has comparable safety and efficacy to the innovator drug when used in obese adults for weight management. METHODS:A phase III multicenter randomized active-controlled non-inferiority trial enrolled adults with obesity across 19 centers in India. Subjects were randomized to the test arm receiving synthetic semaglutide (Alkem Laboratories Limited) or the reference arm administered with innovator semaglutide (Wegovy®, Novo Nordisk) over 24 weeks in a 2:1 ratio. The primary efficacy endpoint was the percentage change in body weight,24 weeks post-intervention. Synthetic semaglutide was established to be non-inferior if the lower bound of the one-sided 97.5% confidence interval for the between-group difference did not exceed 4.5%. RESULTS:Of the 249 randomized participants, 246 (98.8%) completed the study. Mean percentage weight loss after 24 weeks was -14.39 ± 4.17% in the test arm and -14.61 ± 4.36% in the reference arm. The least square-mean difference was 0.15% (-0.93 to 1.24), meeting the predefined non-inferiority criterion. Weight loss >10% was achieved by 86.67% (n=143) in the test arm and 83.95% (n=68) in the reference arm (p = 0.5666), while >15% weight loss occurred in 38.79% (n=64) and 40.74% (n=33), respectively (p = 0.7683). Mean body mass index decreased by -4.93 ± 1.43 kg/m² in the test arm and -5.00 ± 1.50 kg/m² in the reference arm (p = 0.7128). Treatment-emergent adverse events were reported in 55.42% (n=92) of test-arm participants and 54.22% (n=45) of reference-arm participants. CONCLUSIONS:Test semaglutide demonstrated non-inferior efficacy, comparable safety, and similar tolerability to the innovator product.
Abstract Objectives To evaluate the correlation between weight loss and quality of life as assessed by SF-36 (36 item shoer form survey) questionnaire in patients treated with Semaglutide injection for weight management Materials and Methods This phase III, multicentre, randomized, open-label, active-controlled clinical study (CTRI/2025/04/085487) was conducted across 22 study sites in India after receiving regulatory and ethics committee approvals. Total 267 adult patients with BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with the presence of at least one co-morbidity of hypertension, dyslipidaemia and/or type 2 diabetes mellitus were included. Patients were randomized to either test arm to receive synthetic semaglutide injection or reference arm to receive Wegovy® every week subcutaneously for 24 weeks. The primary endpoint was change in body-weight from baseline to week 24. Secondary endpoints included change in BMI, waist circumference, SF-36, and glycaemic measures in diabetic and non-diabetic patients. Safety assessments included incidence of TEAEs and anti-drug/neutralizing antibody. This post-hoc analysis was conducted to evaluate the correlation between weight loss and improvement in quality of life as assessed by SF-36 physical function score. Results The Pearson’s correlation coefficient between change in weight loss and SF-36 physical functioning score was −0.155 with P value = .0467 in test arm. The Pearson’s correlation coefficient between change in weight loss and SF-36 physical functioning score was -0.046 with P value = .6831 in reference arm. There is negative correlation between weight loss and change in SF-36 physical functioning score in both test and reference arm indicating greater reduction in weight loss is associated with more increase in SF-36 score signifying improvement is SF-36 total score. The correlation between weight loss and improvement in SF-36 physical functioning score was statistically significant in test arm. The statistical significance observed in the Pearson correlation analysis in test arm supports the robustness of this association. Conclusions This post-hoc analysis demonstrated that there is improvement in quality of life as measured by SF-36 physical function score with reduction in weight, in patients treated with semaglutide injection for weight management.
Background:Type 2 diabetes mellitus (T2DM) is the most common non-communicable disease affecting over 89.8 million adults in India. Evidence suggests long-acting glucagon-like peptide-1 (GLP-1) receptor agonist improves glycaemic control in the patients with T2DM. This phase 3 trial compared a novel semaglutide injection developed by Zydus Lifesciences Ltd. with the reference biologic in Indian adults with T2DM inadequately controlled on metformin. Methods:In this multicentre, randomised study, 314 patients aged 18-65 years with HbA1c 7.0-10.5 % were randomised 1:1 to once-weekly semaglutide injection (test) or reference semaglutide for 24 weeks. Doses were titrated according to glycaemic targets. The primary endpoint was change in HbA1c at 24 weeks (pre-specified non-inferiority margin of 0.4 percentage points). Secondary endpoints included changes in fasting and post-prandial glucose, body weight, BMI, lipid profile, blood pressure, rescue medication use, safety profile and anti-drug antibody formation. Analyses were conducted on the modified intent-to-treat (mITT) population. Results:Of 314 randomised participants, 274 completed the trial (133 in the test arm and 141 in the comparator arm). HbA1c decreased from 8.36 % to 6.81 % in the test group and from 8.36 % to 6.79 % in the comparator, with a least-squares mean difference of -0.0038 % (95 % CI -0.20 to 0.19), meeting the pre-specified non-inferiority margin. Reductions in body weight (-4.59 vs -4.42 kg), BMI (-1.76 vs -1.68 kg/m2), fasting plasma glucose (-37.5 vs -39.0 mg/dL) and post-prandial plasma glucose (-54.5 vs -55.7 mg/dL) at week 24 were comparable between the groups. Treatment-emergent adverse events (TEAEs) were reported in 58.6 % of patients in the test group and 61.8 % of patients in the comparator group, respectively. Most events were mild and no serious adverse events occurred. Hypoglycaemia was infrequent and mild (1.9 % vs 0 %). Anti-drug antibodies were detected in 2.23 % of samples and had no impact on efficacy. Conclusions:This novel formulation of once-weekly semaglutide injection demonstrated non-inferior glycaemic efficacy, safety & immunogenicity to the reference product in Indian adults with type 2 diabetes. Trial registration:Clinical Trials Registry-India (CTRI/2025/03/082615).
BACKGROUND:Several countries are using fractionated or limited-dose regimens of full dose inactivated polio vaccine (IPV) in infants in addition to oral poliovirus vaccine (OPV), due to procurement cost of IPV and delivery challenges for its campaign use. An adjuvanted dose-sparing IPV (ds-IPV) with around a one-fourth antigen content of the full dose of IPV was developed in India. A non-inferiority trial was conducted to compare the immune response of ds-IPV with IPV in infants. METHODS:A phase 2/3, double-blind, randomised controlled trial was conducted at nine tertiary care hospitals in India. Healthy infants aged 6-8 weeks, who received a birth dose of bivalent OPV were enrolled. Participants with fever or acute infection, and previous receipt or plan to receive any other poliovirus-containing vaccines were excluded. Infants were randomly assigned (1:1; block randomisation managed through an interactive web response system) to receive either ds-IPV or IPV in a three-dose regimen-a single dose of 0·5 mL administered by intramuscular route at age 6 weeks, 10 weeks, and 14 weeks. The vaccine syringes were masked with an opaque peel before administration to maintain masking. All participants were concomitantly administered oral rotavirus vaccine, and injectable DTwP-HB-Hib and pneumococcal conjugate vaccine in the contralateral thigh by the intramuscular route. Blood samples were collected at baseline before the first dose and at 28 days after the third dose for measuring the neutralising antibodies against each poliovirus serotype using microneutralisation assay. The site staff evaluating the study outcomes, participants' parents, and the laboratory personnel were masked to the vaccine allocations. The primary outcome of type-specific percentage seroconversion at 28 days after the third dose of ds-IPV or IPV (non-inferiority margin ≥10%) and secondary outcomes of type-specific geometric mean titres and percentage seroprotection (titre ≥8) were assessed in the per-protocol population as the primary population and the full analysis population as the supportive population. Secondary outcomes on safety evaluation included immediate, solicited, unsolicited, and serious adverse events. This study is registered with the Clinical Trials Registry of India (CTRI/2022/05/042363), and is complete. FINDINGS:Between May 23, 2022, and April 13, 2024, of the 658 participants screened, 648 were eligible and randomly assigned to ds-IPV (n=324) or IPV (n=324). Consent was withdrawn for five participants after randomisation; thus, a total of 643 infants received ds-IPV (n=323) or IPV (n=320). The seroconversion rates for type 1 poliovirus in the ds-IPV and IPV groups were 283 (94·7% [95% CI 91·5 to 96·9]) of 299 participants and 270 (92·8% [89·2 to 95·5]) of 291 participants, respectively, with a difference of 1·9 (95% CI -2·1 to 5·8). The seroconversion rates for type 2 poliovirus in the ds-IPV and IPV groups were 287 (96·3% [93·5 to 98·1]) of 298 participants and 284 (97·9% [95·6 to 99·2]) of 290 participants, respectively, with a difference of -1·6 (-4·7 to 1·5). The seroconversion rates for type 3 poliovirus in the ds-IPV and IPV groups were 291 (97·3% [94·8 to 98·8]) of 299 participants and 288 (99·0% [97·0 to 99·8]) of 291 participants, respectively, with a difference of -1·6 (-3·8 to 0·5). Solicited events, including tenderness, redness, swelling, and fever, were very common (≥10%) in both vaccine groups. No causally related serious adverse events were reported. INTERPRETATION:ds-IPV was immunologically non-inferior to IPV and had a similar safety profile. The new adjuvanted IPV could become an alternative option to IPV. The availability of ds-IPV will support a constant supply of IPV for use in poliovirus-naive and exposed target populations. FUNDING:Serum Institute of India.
Background Pneumococcal conjugate vaccines (PCVs) have markedly reduced childhood pneumococcal diseases, yet serotype replacement and regional heterogeneity remain important challenges. The World Health Organization recommends either a 3p + 0 or 2p + 1 schedule for PCV immunization programmes. BE-PCV14, a 14-valent vaccine, has previously been shown to be non-inferior to PCV13 in a 3p + 0 regimen. In this Phase III trial, we aimed to descriptively compare the immunogenicity and safety of BE-PCV14 and PCV13 in a 2p + 1 schedule in Indian infants. Methods In this randomized, single-blind, multicenter trial, 400 PCV-na & iuml;ve infants (6-8 weeks old) were randomized 1:1 to receive either BE-PCV14 or PCV13; at 6 and 14 weeks, with a booster at 9 months. Serum IgG against 14 vaccine serotypes plus cross-protective 6 A were measured at post primary (28 days post dose 2), pre booster (at 9 months) and post booster (30 days post dose 3) time points. The primary endpoint was the proportion achieving IgG >= 0.35 mu g/mL (seroresponse rate) for the 12 serotypes common to both vaccines at post primary, pre booster and post booster time points. Solicited local and systemic reactions were recorded for 7 days after each dose; unsolicited, and serious adverse events (SAEs) were captured throughout. Findings Between May 2023 and July 2024, 400 participants were enrolled of which 380 (95%) completed the study. Post primary seroresponse rates in the BE-PCV14 arm for common serotypes ranged from 72.6% (95% CI: 65.8, 78.5) (serotype 3) to 100% (95% CI: 98.0, 100.0) (14, 19 F); PCV13 rates ranged from 71.6% (95% CI: 64.9, 77.5) to 100% (95% CI: 98.1, 100.0) (14, 19 F, 19 A). Post booster rates were 87.6% (95% CI: 82.1, 91.6) to 100% (95% CI: 98.0, 100.0) for BE-PCV14 and 85.0% (95% CI: 79.4, 89.4) to 100% (95% CI: 98.1, 100.0) for PCV13. BE-PCV14 elicited high responses against the two additional serotypes, i.e., 22 F: 96.8% (95% CI: 93.1, 98.5), 33 F: 92.5% (95% CI: 87.8, 95.5), and cross-protective 6 A: 93.0% (95% CI: 88.4, 95.9). Of the participants that received BE-PCV14 or PCV13, 33.5% (95% CI: 27.3, 40.3) and 38% (95% CI: 31.6, 44.9) had mild AEs and 11.5% (95% CI: 7.8, 16.7) and 10.5% (95% CI: 7.0, 15.5) had moderate AEs, respectively. Two unrelated SAEs occurred in the BE-PCV14 arm. Interpretation Administered in a 2p + 1 schedule, BE-PCV14 was highly immunogenic, well tolerated, and comparable to PCV13 while broadening serotype coverage. These findings support consideration of BE-PCV14 for routine infant immunization programmes using a 2p + 1 schedule, particularly in settings where the additional serotypes contribute to ongoing pneumococcal disease.
