Safety and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older: two single-center, randomised, double-blind, placebo-controlled, phase 1 and phase 2 trials

AbstractCOVID-19 vaccines from multiple manufacturers are needed to cope with the problem of insufficient supply. We did two single-center, randomised, double-blind, placebo-controlled phase 1 and phase 2 trials to assess the safety, tolerability and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older in China. Eligible participants were enrolled, the ratio of candidate vaccine and placebo within each dose group was 3:1 (phase 1) or 5:1 (phase 2). From August 28, 2020, 168 participants were sequentially enrolled and randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 28 days or 0, 14, 28 days in phase 1 trial. From November 18, 2020, 960 participants were randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 21 days or 0, 14, 28 days in phase 2 trial. The most common solicited injection site adverse reaction within 7 days in both trials was pain. The most common solicited systematic adverse reactions within 7 days were fatigue, cough, sore throat, fever and headache. ELISA antibodies and neutralising antibodies increased at 14 days, and peaked at 28 days (phase 1) or 30 days (phase 2) after the last dose vaccination. The GMTs of neutralising antibody against live SARS-CoV-2 at 28 days or 30 days after the last dose vaccination were highest in the adult high dose group (0, 14, 28 days), with 102.9 (95% CI 61.9–171.2) and 102.6 (95% CI 75.2–140.1) in phase 1 and phase 2 trials, respectively. Specific T-cell response peaked at 14 days after the last dose vaccination in phase 1 trial. This vaccine is safe, and induced significant immune responses after three doses of vaccination.

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Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of the β-Lactamase Inhibitor Vaborbactam (RPX7009) in Healthy Adult Subjects

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00568-16 ◽

2016 ◽

Vol 60 (10) ◽

pp. 6326-6332 ◽

Cited By ~ 42

Author(s):

David C. Griffith ◽

Jeffery S. Loutit ◽

Elizabeth E. Morgan ◽

Stephanie Durso ◽

Michael N. Dudley

Keyword(s):

Plasma Clearance ◽

Healthy Adult ◽

Phase 1 ◽

High Dose ◽

Double Blind ◽

Time Curve ◽

Content Type ◽

Multiple Doses ◽

To Receive ◽

Lactamase Inhibitor

ABSTRACTVaborbactam (formerly RPX7009) is a member of a new class of β-lactamase inhibitor with pharmacokinetic properties similar to those of many β-lactams, including carbapenems. The pharmacokinetics and safety of vaborbactam were evaluated in 80 healthy adult subjects in a first-in-human randomized, placebo-controlled, double-blind, sequential single- and multiple-ascending-dose study. A total of 10 dose cohorts were enrolled in the study, with 6 subjects randomized to receive 250 to 2,000 mg of vaborbactam and 2 subjects randomized to receive placebo in each cohort. Maximum concentrations for vaborbactam were achieved at the end of the 3-h infusion. Vaborbactam exposure (Cmaxand area under the concentration-time curve [AUC]) increased in a dose-proportional manner following multiple doses. There was no evidence of accumulation with multiple doses, consistent with the terminal half-life of ∼2 h. Both the volume of distribution (Vss) and plasma clearance were independent of dose. For the 2,000-mg dose, the plasma clearance was 0.17 ± 0.03 liters/h, the AUC from 0 h to infinity (AUC0–∞) was 144.00 ± 13.90 mg · h/liter, and theVsswas 21.80 ± 2.26 mg · h/liter. Urinary recovery was 80% or greater over 48 h across all dose groups. No subjects discontinued the study due to adverse events (AEs), and no serious AEs (SAEs) were observed. All AEs were mild to moderate and similar among the vaborbactam- and placebo-treated subjects, with mild lethargy as the only unique AE reported with the high dose of vaborbactam. Overall, this study revealed the safety, tolerability, and pharmacokinetic profile of vaborbactam and formed the basis for advancement into patient studies in combination with meropenem, including treatment of patients with carbapenem-resistantEnterobacteriaceae(CRE) infections. (This study is registered at ClinicalTrials.gov under identifier NCT01751269.)

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A Single Administration of AZP-3601, a Novel, Long-Acting PTH Analog, Induces a Significant and Sustained Calcemic Response: Preliminary Data From a Randomized, Double-Blind, Placebo-Controlled Phase 1 Study

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.516 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A254-A254

Author(s):

Soraya Allas ◽

Michel Ovize ◽

Michael D Culler ◽

Clarisse Geraul ◽

Jeroen van de Wetering ◽

...

Keyword(s):

Serum Calcium ◽

Clinical Symptoms ◽

Phase 1 ◽

High Dose ◽

Single Administration ◽

Double Blind ◽

Double Blind Placebo ◽

Healthy Humans ◽

Dose Dependent

Abstract Hypoparathyroidism is a rare disease characterized by a deficiency in parathyroid hormone (PTH) that results in hypocalcemia and hyperphosphatemia. Current treatment approaches, including high dose oral calcium and active vitamin D, as well as recombinant human PTH (1–84), do not provide adequate or consistent control of either serum calcium or clinical symptoms over a full 24-hour period. AZP-3601 is a novel 36 amino-acid PTH analog that has been designed to potently bind to the R0 conformation of the PTH1 receptor, which results in prolonged signaling responses in vitro and prolonged calcemic responses in animals despite having a short circulating half-life. A Phase 1 double-blind, placebo-controlled, single and multiple ascending dose study is being conducted to evaluate the safety, tolerability and pharmacodynamics of AZP-3601 in healthy adults. Here we report data from the first cohorts of the single ascending dose portion of the study. Sequential cohorts of 4 (cohort 1) to 8 (cohort 2 to 4) healthy male subjects aged 18–60 years, with a body mass index of 19–28 kg/m2, were assigned to receive 5, 10, 20 or 40μg of AZP-3601 or placebo at a ratio of 3:1. The study drug was administered in the morning by subcutaneous injection in the abdominal wall and was well tolerated with no remarkable adverse events. As compared with placebo controls, AZP-3601 treatment produced a clear, dose-dependent increase in mean albumin-adjusted serum calcium values from baseline. The normal physiological diurnal variation of albumin-adjusted serum calcium was gradually attenuated with 5 and 10μg AZP-3601, and was completely eliminated with 20μg. With the dose of 40μg AZP-3601, mean albumin-adjusted serum calcium values were significantly increased but stayed within normal laboratory range and remained elevated through at least 24 hours post-administration. We observed a dose-dependent decrease in mean endogenous serum PTH that was significantly correlated with the concomitant increase in mean serum calcium. These data provide initial evidence of the pharmacodynamic effect of AZP-3601 in healthy humans characterized by a sustained calcemic response for at least 24 hours following a single administration.

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Low-dose Ondansetron with Dexamethasone More Effectively Decreases Vomiting after Strabismus Surgery in Children than Does High-dose Ondansetron

Anesthesiology ◽

10.1097/00000542-199801000-00013 ◽

1998 ◽

Vol 88 (1) ◽

pp. 72-75 ◽

Cited By ~ 75

Author(s):

William M. Splinter ◽

Elliot J. Rhine

Keyword(s):

Nitrous Oxide ◽

Dose Group ◽

Low Dose ◽

Maximum Dose ◽

Demographic Data ◽

Strabismus Surgery ◽

High Dose ◽

Healthy Children ◽

Double Blind ◽

Dexamethasone Group

Background Ondansetron and dexamethasone have been observed to decrease the incidence of vomiting by children after general anesthesia. This study compared the effect of high-dose (150 microg/kg) ondansetron with low-dose (50 microg/kg) ondansetron plus 150 microg/kg dexamethasone on the incidence of vomiting after strabismus in children. Methods This study had a double-blind, blocked, stratified, randomized design. With parental consent and Hospital Ethics Committee approval, healthy children aged 2-14 yr who were undergoing elective strabismus surgery were studied. Anesthesia was induced intravenously with propofol or by inhalation with halothane and nitrous oxide. Patients in the high-dose group were given placebo plus 150 microg/kg (maximum dose, 8 mg) of ondansetron intravenously, whereas patients in the low-dose group were given 150 microg/kg dexamethasone (maximum dose, 8 mg) and 50 microg/kg ondansetron intravenously in a double-blind manner. Anesthesia was maintained with halothane and nitrous oxide. All incidences of vomiting occurring as long as 24 h after anesthesia were recorded. Results Three of the 200 patients enrolled in the study were excluded from data analysis. The groups were similar with respect to demographic data and potential confounding variables. Patients vomited from 0-12 times. The low-dose ondansetron plus dexamethasone group had a lower incidence of vomiting, 9% (95% CI = 4-17%) versus 28% (95% CI = 20-38%; P < 0.001). Only 1% of the patients in the low-dose ondansetron plus dexamethasone group vomited while in the hospital. Conclusions Low-dose ondansetron plus dexamethasone is an effective prophylactic antiemetic combination for children undergoing strabismus surgery.

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The Efficacy and Safety of Shen Guo Lao Nian Granule for Common Cold of Qi-Deficiency Syndrome: Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase II Clinical Trial

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/1806461 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11

Author(s):

Xuemei Liu ◽

Juanjuan Fu ◽

Tao Fan ◽

Wei Liu ◽

Hongli Jiang ◽

...

Keyword(s):

Clinical Trial ◽

Phase Ii ◽

Study Protocol ◽

Common Cold ◽

Dose Group ◽

Deficiency Syndrome ◽

Phase Ii Clinical Trial ◽

High Dose ◽

Double Blind ◽

Double Blind Placebo

Background. Common cold is one of the most frequently occurring illnesses in primary healthcare services and represents considerable disease burden. Common cold of Qi-deficiency syndrome (CCQDS) is an important but less addressed traditional Chinese medicine (TCM) pattern. We designed a protocol to explore the efficacy, safety, and optimal dose of Shen Guo Lao Nian Granule (SGLNG) for treating CCQDS. Methods/Design. This is a multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. A total of 240 eligible patients will be recruited from five centers. Patients are randomly assigned to high-dose group, middle-dose group, low-dose group, or control group in a 1 : 1 : 1 : 1 ratio. All drugs are required to be taken 3 times daily for 5 days with a 5-day follow-up period. Primary outcomes are duration of all symptoms, total score reduction on Jackson’s scale, and TCM symptoms scale. Secondary outcomes include every single TCM symptom duration and score reduction, TCM main symptoms disappearance rate, curative effects, and comparison between Jackson’s scale and TCM symptom scale. Ethics and Trial Registration. This study protocol was approved by the Ethics Committee of Clinical Trials and Biomedicine of West China Hospital of Sichuan University (number IRB-2014-12) and registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-15006349).

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Immunogenicity and safety of a third dose, and immune persistence of CoronaVac vaccine in healthy adults aged 18-59 years: interim results from a double-blind, randomized, placebo-controlled phase 2 clinical trial

10.1101/2021.07.23.21261026 ◽

2021 ◽

Author(s):

Hongxing Pan ◽

Qianhui Wu ◽

Gang Zeng ◽

Juan Yang ◽

Deyu Jiang ◽

...

Keyword(s):

Large Scale ◽

Dose Group ◽

Geometric Mean ◽

Development Program ◽

Neutralizing Antibody ◽

Immune Memory ◽

High Dose ◽

Phase 2 ◽

Serious Adverse Events ◽

Double Blind

Background Large-scale vaccination is being implemented globally with CoronaVac, an inactivated vaccine against coronavirus disease 2019 (COVID-19). Immunogenicity and safety profiles of homologous two-dose schedules have been published. We report interim results of immune persistence, and the immunogenicity and safety of a third dose of CoronaVac. Methods In this ongoing, placebo-controlled, double-blind phase 2 trial in 18-to-59-year-olds, we randomly assigned subjects, 1:1:1:1, to one of four schedules to receive a third dose, 28 days or 6 months after two two-dose regimens (14-day or 28-day apart): schedule 1: days 0, 14, 42; schedule 2: days 0, 14, 194; schedule 3: days 0, 28, 56; schedule 4: days 0, 28, 208. For each schedule, participants were randomly assigned to either a medium-dose group (3 μg per 0.5 mL of aluminum hydroxide diluent per dose), a high-dose group (6 μg), or a placebo group (2:2:1). The primary outcome was geometric mean titers (GMTs) of neutralizing antibody to live SARS-CoV-2. Results Overall, 540 participants received a third dose. In the 3 μg group, neutralizing antibody titers induced by the first two doses declined after 6-8 months to below the seropositive cutoff (GMT: 4.1 [95%CI 3.3-5.2] for Schedule 2 and 6.7 [95%CI 5.2-8.6] for Schedule 4). When a third dose was given 6-8 months after a second dose, GMTs assessed 14 days later increased to 137.9 [95%CI 99.9-190.4] for Schedule 2, and 143.1 [95%CI 110.8-184.7] for Schedule 4, approximately 3-fold above Schedule 1 and Schedule 3 GMTs after third doses. Similar patterns were observed for the 6 μg group. The severity of solicited local and systemic adverse reactions reported within 28 days after the third dose were grade 1 to grade 2 in all vaccination cohorts. None of the fourteen serious adverse events were considered to be related to vaccination. Conclusions A third dose of CoronaVac administered 6 or more months after a second dose effectively recalled specific immune response to SARS-CoV-2, resulting in a remarkable increase in antibody levels, and indicating that a two-dose schedule generates good immune memory. Optimizing the timing of a booster dose should take into account immunogenicity, vaccine efficacy/effectiveness, local epidemic situation, infection risk, and vaccine supply. (Funded by the National Key Research and Development Program, Beijing Science and Technology Program and National Science Fund for Distinguished Young Scholars; ClinicalTrials.gov number, NCT04352608.)

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Safety, tolerability, and immunogenicity of a SARS-CoV-2 recombinant spike protein vaccine: a randomised, double-blind, placebo-controlled, phase 1-2 clinical trial (ABDALA Study).

10.1101/2021.11.30.21267047 ◽

2021 ◽

Author(s):

Francisco Hernandez-Bernal ◽

Maria del Carmen Ricardo-Cobas ◽

Yenima Martin-Bauta ◽

Zadis Navarro-Rodriguez ◽

Marjoris Pinera-Martinez ◽

...

Keyword(s):

Placebo Group ◽

Neutralizing Antibodies ◽

Phase 1 ◽

Vaccination Schedule ◽

Phase 2 ◽

Igg Antibodies ◽

Protein Vaccine ◽

Double Blind ◽

Double Blind Placebo ◽

The Third

Aim: To evaluate the safety and immunogenicity of a SARS-CoV-2 recombinant spike protein vaccine (Abdala), administered intramuscularly in different strengths and vaccination schedules. Method: A phase 1-2, randomized, double-blind, placebo-controlled trial was done. Subjects were randomly distributed in 3 groups: placebo, 25 and 50 μg RBD. The product was applied intramuscularly, 0.5 mL in the deltoid region. During the first phase, two immunization schedules were studied: short (0-14-28 days) and long (0-28-56 days). In phase 2, only the short scheme was evaluated. The main endpoints were: safety and proportion of subjects with seroconversion of anti-RBD IgG antibodies to SARS-CoV-2. Blood samples were collected in several points according to the corresponding vaccination schedule to determine the level of RBD-specific IgG antibodies (seroconversion rates and geometric mean of the titers), the percentage of inhibition of RBD-ACE-2 binding and levels of neutralizing antibodies. Results: The product was well tolerated. Severe adverse events were not reported. Adverse reactions were minimal, mostly mild and local (from the injection site), resolved in the first 24-48 hours without medication. In phase 1, at day 56 (28 days after the third dose of the short vaccination schedule, 0-14-28 days) seroconversion of anti-RBD IgG was seen in 95.2 % of the participants (20/21) for the 50 μg group and 81 % of the participants (17/21) for the 25 μg group, and none in the placebo group (0/22); whereas neutralizing antibodies to SARS-CoV-2 were seen in 80 % of the participants (8/10) for the 50 μg group and 94.7% of the participants (18/19) for the 25 μg group. For the long schedule, at day 70 (14 days after the third dose) seroconversion of anti-RBD IgG was seen in 100% of the participants (21/21) for the 50 μg group and 94.7% of the participants (18/19) for the 25 μg group, and none in the placebo group (0/22); whereas neutralizing antibodies to SARS-CoV-2 were seen in 95 % of the participants (19/20) for the 50 μg group and 93.8% of the participants (15/16) for the 25 μg group In phase 2, at day 56 seroconversion of anti-RBD IgG was seen in 89.2% of the participants (214/240) for the 50 μg group, 77.7% of the participants (185/238) for the 25 μg group, and 4.6% in the placebo group (11/239); whereas neutralizing antibodies to SARS-CoV-2 were seen in 97.3% of the participants (146/150) for the 50 μg group and 95.1% of the participants (58/61) for the 25 μg group. Conclusion: Abdala vaccine against SARS-CoV-2 was safe, well tolerated and induced humoral immune responses against SARS-CoV-2 among adults from 19 to 80 years of age.

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Low-Dose Interleukin 2 in Children with Recently Diagnosed Type 1 Diabetes: A Phase 1/2 Randomised, Double-Blind, Placebo-Controlled Dose Finding Study

SSRN Electronic Journal ◽

10.2139/ssrn.3384899 ◽

2019 ◽

Author(s):

Randa Salet ◽

Michelle Rosenzwajg ◽

Roberta Lorenzon ◽

Alexandra Roux ◽

Jean Claude Carel ◽

...

Keyword(s):

Type 1 Diabetes ◽

Low Dose ◽

Phase 1 ◽

Interleukin 2 ◽

Dose Finding ◽

Double Blind ◽

Double Blind Placebo ◽

Finding Study ◽

Dose Finding Study

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DESTINATION: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma

Respiratory Research ◽

10.1186/s12931-020-01541-7 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Andrew Menzies-Gow ◽

Sandhia Ponnarambil ◽

John Downie ◽

Karin Bowen ◽

Åsa Hellqvist ◽

...

Keyword(s):

High Dose ◽

Treatment Cessation ◽

Uncontrolled Asthma ◽

Phase 3 ◽

Double Blind ◽

Double Blind Placebo ◽

Long Term Treatment ◽

To Receive

Abstract Background Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. The efficacy, safety and oral corticosteroid-sparing potential of tezepelumab are being investigated in two ongoing, phase 3, randomized, double-blind, placebo-controlled studies (NAVIGATOR [NCT03347279] and SOURCE [NCT03406078]). DESTINATION (NCT03706079) is a long-term extension (LTE) of these studies. Methods DESTINATION is a randomized, double-blind, placebo-controlled LTE study in adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma who are receiving treatment with medium- or high-dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids. The study population will comprise patients who complete the 52- and 48-week NAVIGATOR and SOURCE studies, respectively. Patients who were randomized to receive tezepelumab 210 mg every 4 weeks (Q4W) in either predecessor study will continue to receive this regimen for 1 year; those who were previously randomized to receive placebo will be re-randomized (1:1) to receive either tezepelumab 210 mg Q4W or placebo for 1 year. Patients will receive their prescribed controller medications throughout DESTINATION and study physicians will have the opportunity to down- or up-titrate dosage of these medications, if appropriate. The primary objective is to evaluate the long-term safety and tolerability of tezepelumab over 104 weeks (inclusive of the treatment period of either predecessor study). The secondary objective is to assess the long-term effect of tezepelumab on asthma exacerbations. Patients recruited from SOURCE will be followed up post-treatment for 12 weeks. Patients recruited from NAVIGATOR who complete 100 weeks of tezepelumab treatment will be eligible for either 12 weeks of follow-up or a 36-week extended follow-up during which the clinical benefit of tezepelumab after treatment cessation will be investigated. Discussion DESTINATION will evaluate the long-term safety, tolerability and efficacy of tezepelumab versus placebo with continued dosing for up to 2 years. DESTINATION will also evaluate the clinical effect of tezepelumab after treatment cessation. This LTE study aims to elucidate the long-term safety implications of receiving tezepelumab and to assess its potential long-term treatment benefits in patients with severe, uncontrolled asthma. Trial registration NCT03706079 (ClinicalTrials.gov). Registered 15 October 2018.

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Double-Blind, Randomized, Three-Armed, Placebo-Controlled, Clinical Investigation to Evaluate the Benefit and Tolerability of Two Dosages of IQP-AE-103 in Reducing Body Weight in Overweight and Moderately Obese Subjects

Journal of Obesity ◽

10.1155/2019/3412952 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Ralf Uebelhack ◽

Udo Bongartz ◽

Stephanie Seibt ◽

Gordana Bothe ◽

Pee Win Chong ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Placebo Group ◽

Body Fat ◽

Dose Group ◽

Low Dose ◽

Clinical Investigation ◽

Controlled Trial ◽

High Dose ◽

Double Blind

Objective. This study was performed to determine the efficacy and tolerability/safety of IQP-AE-103 on body weight reduction in overweight to moderately obese adults. Methods. A double-blind, randomized, placebo-controlled trial involved one hundred and eight subjects (BMI between 25 and 35 kg/m2) that were randomly assigned to either the low-dose or the high-dose IQP-AE-103 group, or the placebo group. Following a 2-week run-in period, subjects received two capsules of investigational product after three daily main meals for 12 weeks. Subjects were instructed to maintain a nutritionally balanced hypocaloric diet according to the individual’s energy requirement. Body weight, body fat, and waist and hip circumference were measured at baseline, and after 2, 4, 8, and 12 weeks. Subjects also rated their feelings of hunger and fullness using visual analogue scales, and food craving on a 5-point scale at the same time intervals. Blood samplings for safety laboratory parameters were taken before and at the end of the study. Results. After 12 weeks of intake, the high-dose IQP-AE-103 group had a significantly greater weight loss compared with the placebo (5.03 ± 2.50 kg vs. 0.98 ± 2.06 kg, respectively; p<0.001) and the low-dose group (3.01 ± 2.19 kg; p=0.001). The high-dose group experienced a decrease in body fat of 3.15 ± 2.41 kg compared with a decrease of 0.23 ± 2.74 kg for the placebo group (p<0.001). High-dose IQP-AE-103 also decreased the feeling of hunger in 66% subjects. A beneficial effect of IQP-AE-103 on the lipid metabolism was also demonstrated in the subgroup of subjects with baseline total cholesterol levels above 6.2 mmol/L. No side effects related to the intake of IQP-AE-103 were reported. Conclusions. These findings indicate that IQP-AE-103 could be an effective and safe weight loss intervention. This trial is registered with NCT03058367.

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