Safety and pharmacokinetics of BXQ-350 in a phase 1a and 1b trial of solid tumors and high-grade glioma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13531-e13531 ◽  
Author(s):  
Olivier Rixe ◽  
John Charles Morris ◽  
Vinay K. Puduvalli ◽  
John L. Villano ◽  
Trisha Michel Wise-Draper ◽  
...  
Keyword(s):  
Adverse Events ◽  
Dose Escalation ◽  
Phase 1 ◽  
High Grade Glioma ◽  
High Grade ◽  
Antitumor Effects ◽  
Serious Adverse Events ◽  
Blood Pressure Elevation ◽  
Saposin C ◽  
Ongoing Phase

e13531 Background: BXQ-350 is composed of the multifunctional, lysosomal-activator protein Saposin C and phosphatidylserine lipid with demonstrated antitumor effects in vitro and in vivo. In this abstract we update the safety and pharmacokinetic (PK) profile based on an ongoing Phase 1 trial. Methods: BXQ-350 was administered in a Phase 1a dose-escalation trial (NCT02859857), and an ongoing Phase 1b trial (data cut off at max of 6 cycles, 01DEC2018) to refractory solid tumor/high-grade glioma patients (pts). In Phase 1a, pts received escalating IV BXQ-350 doses of 0.7, 1.1, 1.4, 1.8, or 2.4 mg/kg on days 1, 2, 3, 4, 5, 8, 10, 12, 15, 22 (cycle 1), 29 (cycle 2), and thereafter 28-day cycles. PK was assessed over a 24-hr period following the first dose. The Saposin C level was analyzed by ELISA and PK parameters were calculated using noncompartmental methods. Results: The 1a cohort of 18 pts (age 24-69) had a median of 3 cycles and 1b cohort of 20 pts (age 31-80) had median of 2 cycles with no treatment-related serious adverse events to date. Moderately severe related adverse events (AEs, n case, n events) are reported with serious non-related events. The most common treatment-related AE was fatigue (2 at dose 1.1, 2 at 1.8, 1 at 2.4mg/kg and 3 in 1b), at 2.4 mg/kg, 1 pt had moderate blood pressure elevation. Exposures in the 1.4 and 1.8 mg/kg cohorts were less than dose-proportional, likely due to higher clearance in those groups. The overall mean clearance and half-live values were 66.8 (mL/kg/h) and 4.03 h, respectively. Conclusions: BXQ-350 has had no serious related AEs during dose-escalation or in the on-going trial supporting a tolerable safety profile at 2.4 mg/kg. Clinical trial information: NCT02859857. [Table: see text]

A Phase 1 Dose-Escalation Study of Oral 5-Aminolevulinic Acid in Adult Patients Undergoing Resection of a Newly Diagnosed or Recurrent High-Grade Glioma

Neurosurgery ◽  
2017 ◽  
Vol 81 (1) ◽  
pp. 46-55 ◽  
Author(s):  
Jeffrey W. Cozzens ◽  
Barbara C. Lokaitis ◽  
Brian E. Moore ◽  
Devin V. Amin ◽  
José A. Espinosa ◽  
...  
Keyword(s):  
United States ◽  
Adverse Events ◽  
Dose Level ◽  
Dose Escalation ◽  
Aminolevulinic Acid ◽  
Medical Center ◽  
Phase 1 ◽  
High Grade Glioma ◽  
The United States ◽  
High Grade

Abstract BACKGROUND: The utility of oral 5-aminolevulinic acid (5-ALA)/protoporphyrin fluorescence for the resection of high-grade gliomas is well documented. This drug has received regulatory approval in Europe but awaits approval in the United States. OBJECTIVE: To identify the appropriate dose and toxicity or harms of 5-ALA used for enhanced intraoperative visualization of malignant brain tumors, reported from a single medical center in the United States. METHODS: Prior to craniotomy for resection of a presumed high-grade glioma, individuals were given oral 5-ALA as part of a rapid dose-escalation scheme. At least 3 patients were selected for each dose level from 10 to 50 mg/kg in 10 mg/kg increments. Adverse events, intensity of tumor fluorescence, and results of biopsies in areas of tumor and the tumor bed under white light and deep blue light were recorded. RESULTS: A total of 19 patients were studied in this phase 1 study. Serious adverse events were unrelated to the ingestion of 5-ALA. At the highest dose level studied (50 mg/kg), 2 out of 6 patients were observed to have transient dermatologic redness and peeling. These were grade 1 adverse events, which were not serious enough to be dose limiting. Patients at higher dose levels (>40 mg/kg) were more likely to have strong tumor fluorescence. There were no instances of false positive fluorescence. CONCLUSION: The use of 5-ALA for brain tumor fluorescence is safe and effective to a dose of 50 mg/kg. Dose-limiting toxicity was not reached in this study.

A phase I study to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activities of daily oral BAL101553, a novel tumor checkpoint controller (TCC) in adult patients with progressive or recurrent glioblastoma (GBM) or high-grade glioma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS2601-TPS2601
Author(s):  
Alvaro Henrique Ingles Garces ◽  
Elizabeth R. Plummer ◽  
Juanita Suzanne Lopez ◽  
Rebecca Sophie Kristeleit ◽  
Julie MacDonald ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Dose Escalation ◽  
Spindle Assembly Checkpoint ◽  
Phase 1 ◽  
High Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
Tumor Cell Death ◽  
Antitumor Activities ◽  
Dose Escalation Study

TPS2601 Background: BAL101553 (prodrug of BAL27862) is a novel TCC that promotes tumor cell death by modulating the spindle assembly checkpoint. BAL27862 is a lipophilic, small molecule (MW 387) shown in rats to penetrate the brain (1:1 plasma ratio) and has shown promising antitumor activity in orthotopic preclinical models of GBM as monotherapy or in combination with radiotherapy (RT) with/without chemotherapy. In a completed Phase 1 study with 2-h IV infusions (Days 1, 8, 15, q28d, NCT01397929 , CDI-CS-001, Lopez et al. J Clin Oncol 34, 2016 suppl; 2525), dose-limiting vascular effects were observed and appeared Cmax related. Preclinical data suggest that antiproliferative effects of BAL101553/27862 are driven by exposure (AUC); thus vascular toxicity and antitumor activity are mediated by different PK drivers. In this ongoing study (NCT02490800, CDI-CS-002), daily oral BAL101553 was initially examined in solid-tumor patients; no vascular toxicities were observed at doses up to the MAD of 30 mg QD. Given this absence, the study was amended to enroll separate cohorts of patients with progressive or recurrent GBM or high-grade glioma. Methods: This is an ongoing multicenter, open-label, Phase 1 dose-escalation study using a 3+3 design to determine the MTD, characterize dose-limiting toxicities and assess the PK, PD and antitumor activities of daily oral administration of BAL101553 in consecutive 28-day cycles at a starting dose of 8 mg QD. Patients with histologically-confirmed GBM or high-grade glioma, with progressive or recurrent disease after prior RT with/without chemotherapy, are eligible for enrollment. This includes patients with histologically-confirmed low-grade glioma with unequivocal evidence by imaging of transformation to high-grade glioma. Adverse events are assessed using CTCAEv4; tumor response by RANO (every 2 cycles). The dose escalation allows for doubling of dose levels depending on observed toxicities. PD assessments include circulating tumor cells. PK profiles are assessed throughout the first two treatment cycles. Clinical trial information: NCT02490800.

scholarly journals QOLP-23. PHASE II RANDOMISED PLACEBO-CONTROLLED DOUBLE-BLIND STUDY OF ACETAZOLAMIDE VERSUS PLACEBO FOR CEREBRAL OEDEMA IN RECURRENT AND/OR PROGRESSIVE HIGH-GRADE GLIOMA REQUIRING TREATMENT WITH DEXAMETHASONE

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii179-ii180
Author(s):  
Meera Agar ◽  
Anna Nowak ◽  
Elizabeth Hovey ◽  
Elizabeth Barnes ◽  
John Simes ◽  
...  
Keyword(s):  
Adverse Events ◽  
Dose Reduction ◽  
Primary Endpoint ◽  
Performance Status ◽  
Case Series ◽  
High Grade Glioma ◽  
Double Blind Study ◽  
High Grade ◽  
Serious Adverse Events ◽  
Double Blind

Abstract INTRODUCTION Symptoms of raised intracranial pressure (ICP) in recurrent or progressive high-grade glioma (HGG) generally require corticosteroid treatment, often causing toxicity with variable effects on reversing ICP symptoms. Acetazolamide reduces ICP in other clinical settings including case series in glioma. AIM To explore whether addition of oral acetazolamide enables safe dexamethasone dose reduction in management of raised ICP in recurrent and/or progressive HGG. METHODS Participants had recurrent, progressive and/or persistent residual HGG requiring recommencement of dexamethasone, dose increase or dexamethasone dependency; prior/current bevacizumab was an exclusion. Eligible participants were randomised 1:1 to acetazolamide 250mg twice daily or placebo for 8 weeks. Standardised protocols were used for dexamethasone dose changes in both arms, with planned dose decrease from day 5 once ICP symptoms were stable. The primary endpoint was a composite of dexamethasone dose reduction and stability of performance status. Secondary endpoints included toxicity and feasibility (accrual and compliance). RESULTS Thirty participants of a planned sample of 84 were enrolled (mean age 58 y (32-89)) from 7 Australian sites. The mean baseline dexamethasone dose was 6.2mg (4-16mg). Mean duration on treatment was 38 days (4-57) in placebo group and 31 days (3-60) in acetazolamide group, with 9 participants (30%) completing all study treatment (6 placebo, 3 acetazolamide). Study withdrawal was due to adverse events (n=6 (1 placebo, 5 acetazolamide)) and disease progression (n=6 (3 per arm)). Four participants (13%) (2 per arm) were stable responders meeting the primary endpoint criteria (≥50% corticosteroid dose reduction from baseline by 28 days maintained for 7 days, and no deterioration in performance status). Ten participants experienced a total of 13 serious adverse events (acetazolamide arm: 5 participants (33%), 6 events, 2 related). DISCUSSION The addition of acetazolamide did not facilitate dexamethasone reduction. The study closed early due to poor accrual and increasing availability of bevacizumab.

Results of a Phase 1/2 Study for KW-0761, a Monoclonal Antibody Directed Against CC Chemokine Receptor Type 4 (CCR4), In CTCL Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 962-962 ◽  
Author(s):  
Madeleine Duvic ◽  
Lauren Pinter-Brown ◽  
Francine M Foss ◽  
Lubomir Sokol ◽  
Jeffrey Jorgensen ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Adverse Events ◽  
Chemokine Receptor ◽  
Dose Escalation ◽  
Research Funding ◽  
Phase 1 ◽  
Open Label ◽  
Serious Adverse Events ◽  
Cc Chemokine ◽  
Overall Response

Abstract Abstract 962 Introduction: KW-0761 is a defucosylated, humanized, monoclonal antibody with enhanced antibody dependent cellular cytotoxicity (ADCC; Potelligent®) that binds to CC chemokine receptor 4 (CCR4). CCR4 is over expressed in PTCL and CTCL, and is a potential target for anti-neoplastic therapy in these disorders. Study Design: This multicenter, open-label, dose escalation phase 1/2 study is in patients with previously treated PTCL and CTCL (including MF and SS). The study is composed of a dose escalation phase (Phase 1) and preliminary assessment of safety and efficacy (Phase 2). The phase 1 portion is a standard 3+3 design at doses of 0.1, 0.3, and 1 mg/kg. In the first treatment course, KW-0761 is administered i.v. once a week for four weeks, followed by a 2-week observation period. Subjects demonstrating a response or maintaining stable disease may receive additional infusions of KW-0761 every other week until progression or withdrawal from study. For CTCL patients, the overall global response score is a composite of response in all compartments (skin, lymph nodes, viscera). For subjects with Sezary Syndrome (SS), response in blood is also considered for overall response. For PTCL patients, the response is based on criteria defined by the International Working Group (IWG). Results: Forty-two patients who had received at least one prior systemic therapy (median 5; range 1–17) are enrolled. The median age is 67 (range: 35–85) years with more males (57%) than females (43%). A total of 40 patients received at least four doses of KW-0761 at 0.1 mg/kg (n=3), 0.3 mg/kg (n=3) and 1 mg/kg (n=34). There are no dose limiting toxicities (DLT) or drug-related serious adverse events (SAEs) reported in the dose escalation portion of the study. Most observed adverse events (AEs) are mild to moderate in severity. There does not appear to be any dose relationship with the incidence or severity of the AEs. The most frequent AEs are chills, headache, nausea, pyrexia, infusion related reactions and back pain. There does not seem to be an increase in the rate of infections associated with the use of this drug. Six of 42 patients who received at least one dose of KW-0761 developed a new skin eruption not consistent with the patients' underlying disease, including one grade 3 hypersensitivity rash with eosinophils. No significant hematologic AEs have been observed except for lymphopenia which is due to the pharmacologic effect of the drug. A total of 38 patients (23 with MF; 15 with SS) are evaluable for efficacy (only one subject with PTCL was enrolled and is not included in this analysis). A summary of all patients evaluable for efficacy to date is presented in the table belowa: Conclusions: KW-0761 is well tolerated at doses of 0.1–1.0 mg/kg. The MTD has not been reached in this study. The overall response rate is 39% for all patients in the phase 1/2 trial with a higher rate in SS patients (47%) versus MF patients (35%). Additionally, 12 of 15 SS patients had a response in the blood, including 7 CRs. These promising results warrant further clinical studies using KW-0761 in refractory or relapsed CTCL patients. Disclosures: Duvic: Kyowa-kirin-pharma.com: Consultancy, Research Funding. Pinter-Brown:Kyowa-Kirin: Consultancy, Research Funding. Foss:Kyowa-Kirin: Consultancy, Research Funding. Sokol:Kyowa-Kirin: Research Funding. Jorgensen:Kyowa Hakko Kirin Co, Ltd.: Research Funding. Spitalny:Kyowa-Kirin: Employment. Kim:Kyowa-Kirin: Consultancy, Research Funding.

A phase I study of the tolerability, safety, pharmacokinetics and preliminary antitumor effects of KBP-5209, a novel pan-HER inhibitor, in patients with advanced solid tumors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2565-2565
Author(s):  
Sarina Anne Piha-Paul ◽  
Sunil Sharma ◽  
Chengkon Shih ◽  
Bert H. O'Neil ◽  
Qinghong Zhou ◽  
...  
Keyword(s):  
Adverse Events ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Human Study ◽  
Study Drug ◽  
Nausea And Vomiting ◽  
Advanced Solid Tumors ◽  
Irreversible Inhibitor ◽  
Antitumor Effects ◽  
Serious Adverse Events

2565 Background: KBP-5209 is a novel potent and irreversible inhibitor of tyrosine kinases of the human epidermal growth factor receptor (EGFR) family that preclinically has demonstrated potent antitumor activities in esophageal and gastric cancers and NSCLC. Methods: This first-in-human study (NCT02442414) was conducted to determine tolerability, safety, pharmacokinetics and antitumor activity of KBP-5209 administered QD or BID in patients (pts) with advanced solid tumors. Dose escalation (DE) initially was based on a modified accelerated titration plan and then shifted to a standard 3+3 design. The starting dose was 20 mg QD. Eligible patients were adults with advanced, refractory solid tumors with ECOG PS < 1. A cycle was 28 days. DLTs were evaluated for during the first cycle. DE enriched for patients with tumors having molecular alterations in EGFR or HER2/3. Dose escalation continues so dose expansion has not initiated. Results: As of 26 Nov, 2016, 23 pts (15 females, 8 males) are a part of the evaluable population with a median age 57 (37-79) treated at doses of 20mg (1), 40mg (3), 60mg (7), 70mg (4), 80mg (6) QD and 20mg BID (2).Tumor types included breast (6), CRC (4), ovarian (3), H&N (2), sarcoma (2), and NSCLC, sinus, gastric, gallbladder, pancreas, CUP tumor (1 each). Tumor genetic profiles were available for 20 pts. DLTs were G3 diarrhea, nausea, and vomiting, which occurred in 1 pt at 80mg QD and G3 Diarrhea, occurring in 1pt at 80mg QD. The most common adverse events related to study drug were diarrhea (60.9%), nausea (47.8%), vomiting (43.5%), fatigue (21.7%), decreased appetite (17.4%) and lipase increased (17.4%). Serious adverse events (SAEs) related to study drug were reported in 4pts: diarrhea (1 pt, 70mg QD; 1pt, 80mg QD), nausea and vomiting (1pt, 70mg QD), and diarrhea, nausea and vomiting (1 pt, 80mg QD). Stable disease has been observed in 7pts up to 24 weeks, in which 2/28 pts (7%) achieved tumor shrinkage. Conclusions: Based on the present data, KBP-5209 has been well tolerated with a safety profile similar to other pan-HER inhibitors. For QD dosing, maximum tolerated dose has been identified as 70mg QD. The BID dose escalation continues. Clinical trial information: NCT02442414.

A first-in-human phase I dose escalation of YH001, an anti-CTLA-4 monoclonal antibody (mAb) in combination with toripalimab (anti-PD-1 mAb) in patients with advanced solid tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2577-2577
Author(s):  
Vinod Ganju ◽  
Adam Cooper ◽  
Bo Gao ◽  
Kate Wilkinson
Keyword(s):  
Adverse Events ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Phase 1 ◽  
Gastroesophageal Junction ◽  
Advanced Solid Tumors ◽  
Dose Escalation Study ◽  
Gastroesophageal Junction Cancer ◽  
Anti Cancer ◽  
Ongoing Phase

2577 Background: YH001 is a humanized anti -hCTLA-4 IgG1 mAb that relieves CTLA-4-mediated immunosuppression, and thereby enhances the T-cell-mediated antitumor immune response. Pre-clinical data have shown potent anti-cancer activity when combined with anti-PD-1 mAb. Methods: This is an ongoing phase 1 dose-escalation study. Patients (pts) with advanced solid tumors received YH001 by IV administration at 0.05 to 6.0 mg/kg for 1 cycle (21 days) then in combination with Toripalimab (anti-PD-1 mAb) at 240 mg Q3W for 4 cycles. An accelerated titration method followed by the standard “3+3” design was utilized to evaluate safety, tolerability and preliminary efficacy. Results: As of 31-Dec-2020 data cut-off, 10 pts were enrolled and treated at 0.05 mg/kg (n = 2), 0.1 mg/kg (n = 3), 0.3 mg/kg (n = 3) and 1 mg/kg (n = 2). The median age was 62 years (range 46-74). Baseline ECOG scores were 0 (n = 8), 1(n = 2) with all pts progressed after a median of 2 prior lines of available standard therapy (range 1-4) including 1 pt progressed after immunotherapy of pembrolizumab. There were no dose limiting toxicities (DLT) observed. No severe adverse events (SAEs), Grade (G) 3 or above adverse events (AEs) and AEs leading to treatment discontinuation were reported. Twelve drug related AEs were all G1/2 events including 2 G2 AEs (1 rash maculopapular at 0.05mg/kg, 1 hypothyroidism at 0.1mg/kg), 10 G1 AEs (1 hypotension, 1 dry skin, 1 pruritus at 0.05mg/kg; 1 rash, 1 rash macular, 1 hyperthyroidism, 2 rash pruritus at 0.1mg/kg, 2 fatigues at 0.3mg/kg). Among 7 patients having imaging tumor assessment by RECIST v1.1, there were 4 SD, including 1 at 0.05 mg/kg with tongue carcinoma at week 8 assessment, 1 at 0.1 mg/kg with nasopharyngeal carcinoma at week 8 and 15 assessment, 2 at 0.3 mg/kg with gastroesophageal junction cancer and uterus leiomyosarcoma at week 8. Conclusions: YH001 combined with Toripalimab is safe and tolerable up to 1 mg/kg dose level. Updated safety and preliminary efficacy data will be presented. Clinical trial information: NCT04481009.

scholarly journals Gemcitabine Plus Radiation Therapy for High-Grade Glioma: Long-Term Results of a Phase 1 Dose-Escalation Study

2016 ◽  
Vol 94 (2) ◽  
pp. 305-311 ◽  
Author(s):  
Michelle M. Kim ◽  
Sandra Camelo-Piragua ◽  
Matthew Schipper ◽  
Yebin Tao ◽  
Daniel Normolle ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Dose Escalation ◽  
Phase 1 ◽  
High Grade Glioma ◽  
Long Term Results ◽  
High Grade ◽  
Dose Escalation Study

scholarly journals ACTR-64. PHASE 2 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS AND CLINICAL ACTIVITY OF PI3K/mTOR INHIBITOR GDC-0084 IN GBM PATIENTS WITH UNMETHYLATED O6-METHYLGUANINE-METHYLTRANSFERASE (MGMT) PROMOTER STATUS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi28-vi28
Author(s):  
Patrick Wen ◽  
John DeGroot ◽  
James Battiste ◽  
Samuel Goldlust ◽  
James Garner ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Mtor Inhibitor ◽  
Phase 1 ◽  
Mammalian Target Of Rapamycin ◽  
High Grade Glioma ◽  
Clinical Activity ◽  
High Grade ◽  
Newly Diagnosed ◽  
Open Label ◽  
Once Daily

Abstract BACKGROUND GDC-0084 is a potent, oral, selective small molecule inhibitor of class I phosphoinositide 3-kinase and mammalian target of rapamycin (PI3K/mTOR). GDC-0084 crosses the blood-brain barrier and achieves a brain / plasma ratio of approximately 1.0. GDC-0084 was given as once daily dosing in a phase 1 study (Wen et al, J Clin Oncol 34, 2016(15) suppl.2012) in 47 patients with recurrent high-grade gliomas. The adverse events were generally consistent with the established PI3K/mTOR inhibitor class-effects. The MTD identified was 45mg once daily. METHODS The current study is conducted in the newly diagnosed GBM patient with unmethylated MGMT promotor status upon completion of standard adjuvant XRT/TMZ. It has a 2-part design: an open-label, dose-escalation phase to assess the safety, tolerability, MTD (Part 1, followed by an expansion cohort (Part 2) commencing once MTD is established. Dose-escalation started at 60mg, and progressed in 15mg increments, per standard 3 + 3 rules. Part 2 recruits 20 patients, who are randomized to take GDC-0084 at the identified MTD, in fed and fasted states. RESULTS Part 1 of the study is complete. There were no DLTs among 3 pts treated at the 60mg. Among 6 pts treated at 75mg, DLTs were identified as hyperglycaemia (symptomatic) and oral mucositis. Adverse effects seen were generally modest, manageable and consistent with the PI3K-class. PK parameters are in line with phase 1 data. Part 2 recruitment is ongoing. CONCLUSION GDC-0084 displays a safety profile consistent with previous data in recurrent high-grade glioma but appears better tolerated in the newly diagnosed GBM setting. An MTD of 60mg is identified.

scholarly journals Safety and Immunogenicity of Nanocovax, a SARS-CoV-2 Recombinant Spike Protein Vaccine

2021 ◽  
Author(s):  
Thuy P Nguyen ◽  
Quyet Do ◽  
Lan T Lan ◽  
Duc V Dinh ◽  
Hiep Khong ◽  
...  
Keyword(s):  
Adverse Events ◽  
Aluminum Hydroxide ◽  
Dose Escalation ◽  
Phase 1 ◽  
Vaccine Safety ◽  
Antibody Responses ◽  
Phase 2 ◽  
Serious Adverse Events ◽  
To Receive ◽  
Trial Phase

Background Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminum hydroxide adjuvant. Methods We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 microgram (mcg), 50 mcg, and 75 mcg doses, aluminum hydroxide adjuvanted). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2 which involved in 560 healthy adults, the primary outcomes are vaccine safety; and anti-S IgG antibody response. Secondary outcomes were surrogate virus neutralization, wild-type SARS-CoV-2 neutralization, and T-cell responses by intracellular staining (ICS) for interferon gamma (IFNg). We performed primary analyses at day 35 and day 42. Results For phase 1 study, no serious adverse events (SAE) were observed for all 60 participants. Most adverse events (AE) were grade 1 and disappeared shortly after injection. For phase 2 study, after randomization, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive placebo. Reactogenicity was absent or mild in the majority of participants and of short duration (mean, ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. There was no statistical difference in antibody responses among dose strengths on Day 42, in terms of anti S-IgG level and neutralizing antibody titer. Conclusions Up to 42 days, Nanocovax vaccine was safe, well tolerated and induced robust immune responses. We propose using Nanocovax 25 mcg for Phase 3 to evaluate the vaccine efficacy. (Research funded by Nanogen Pharmaceutical Biotechnology JSC., and the Ministry of Science and Technology of Vietnam; ClinicalTrials.gov number, NCT04683484.)

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