EXTENDED ABSORPTION OF LIOTHYRONINE FROM POLY-ZINC-LIOTHYRONINE (PZL): RESULTS FROM A PHASE 1, DOUBLE-BLIND, RANDOMIZED, AND CONTROLLED STUDY IN HUMANS

Background : ALX-0081 is a bivalent Nanobody ® based on the variable domain of naturally occurring heavy-chain only antibodies. It binds with high affinity to the A1 domain of von Willebrand Factor (vWF) and thereby blocks the interactions between platelets and vascular collagen. It selectively prevents thrombus formation under high shear stress conditions. Aim : Test ALX-0081 single IV infusions (60 minutes) dosed from 0.5mg to 12mg total in 40 male healthy volunteers in double-blind, randomized, placebo controlled study and assess pharmacokinetic (PK), pharmacodynamic (PD), safety and immunogenicity. Results : ALX-0081 displayed non-linear pharmacokinetic properties, following a 2 compartment model. Ristocetin induced platelet aggregation (RIPA) was analyzed as marker for PD effect with full inhibition (defined as measured levels dropping <10%) observed at ALX-0081 concentrations of ~ 400ng/ml. All subjects dosed ≥ 2mg achieved full RIPA inhibition at 1h post-dosing for maximum of 12h. ALX-0081 treatment was well tolerated and safe, no signs of bleeding were reported and no immunogenic response was detected. Target related mild and transient reductions of vWF and FVIII plasma levels were observed and all events were fully reversible. Phase Ib study design : double-blind, randomized, placebo controlled, multiple ascending dose study. ALX-0081 added to standard anti-thrombotic regimen (ASA, clopidogrel, UFH) in patients with stable angina undergoing elective PCI. Single-dose escalation will be followed by multiple dosing (up to 4 doses in 24h). Dose escalation will be guided by safety and efficacy marker. Endpoints: safety, pharmacological profile, biomarker (RIPA, RICO and ACT) and early clinical outcome (MACE, IMR, molecular marker). Conclusion : ALX-0081 can be administered safely over a wide range of dose-regimen. First results of the phase Ib study in stable angina patients will be presented.

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A Phase 1 Randomized Placebo-Controlled Study to Assess the Safety, Immunogenicity and Genetic Stability of a New Potential Pandemic H7N9 Live Attenuated Influenza Vaccine in Healthy Adults

Vaccines ◽

10.3390/vaccines8020296 ◽

2020 ◽

Vol 8 (2) ◽

pp. 296

Author(s):

Irina Kiseleva ◽

Irina Isakova-Sivak ◽

Marina Stukova ◽

Marianna Erofeeva ◽

Svetlana Donina ◽

...

Keyword(s):

Adverse Events ◽

Influenza Vaccine ◽

Phase 1 ◽

Healthy Adults ◽

Controlled Study ◽

Temperature Sensitive ◽

Serious Adverse Events ◽

Double Blind ◽

Human Influenza Virus ◽

Live Attenuated Influenza Vaccine

This study describes a double-blind randomized placebo-controlled phase I clinical trial in healthy adults of a new potential pandemic H7N9 live attenuated influenza vaccine (LAIV) based on the human influenza virus of Yangtze River Delta hemagglutinin lineage (ClinicalTrials.gov Identifier: NCT03739229). Two doses of H7N9 LAIV or placebo were administered intranasally to 30 and 10 subjects, respectively. The vaccine was well-tolerated and not associated with increased rates of adverse events or with any serious adverse events. Vaccine virus was detected in nasal swabs during the 6 days after vaccination or revaccination. A lower frequency of shedding was observed after the second vaccination. Twenty-five clinical viral isolates obtained after the first and second doses of vaccine retained the temperature-sensitive and cold-adapted phenotypic characteristics of LAIV. There was no confirmed transmission of the vaccine strain from vaccinees to placebo recipients. After the two H7N9 LAIV doses, an immune response was observed in 96.6% of subjects in at least one of the assays conducted.

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Pharmacokinetics and Safety of Icotinib Hydrochloride Cream in Patients with Mild to Moderate Chronic Plaque Psoriasis: A Randomized Double-Blind Vehicle-Controlled Phase 1 Study

BioMed Research International ◽

10.1155/2019/9072683 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8

Author(s):

Lunfei Liu ◽

Honggang Lou ◽

Jiong Zhou ◽

Ying Shen ◽

Min Zheng ◽

...

Keyword(s):

Plaque Psoriasis ◽

Phase 1 ◽

Vehicle Group ◽

Controlled Study ◽

Application Site ◽

Dependent Manner ◽

Local Tolerability ◽

Phase 1 Study ◽

Double Blind ◽

Quality Life

Objective.This phase I study aimed to systematically assess the safety, local tolerability, pharmacokinetics, and preliminary efficacy of topical icotinib hydrochloride cream in patients with mild to moderate plaque psoriasis.Materials and Methods.Eligible Chinese adult patients with mild to moderate psoriasis were assigned to the icotinib cream or vehicle group. Icotinib cream with increasing concentrations (0.5%, 1.0%, 2.0%, and 4.0%) or vehicle were administered by the fingertip unit method to the skin lesions twice a day for 4 weeks. Safety assessments included the incidence and severity of adverse events (AEs), local tolerability at the treatment area, vital signs, and laboratory examinations. Plasma levels of icotinib were also measured for the pharmacokinetics calculation. The efficacy was preliminarily explored by assessing the improvement in the severity level using Target Plaque Severity Score (TPSS) and overall improvement using the Psoriasis Area Severity Index (PASI) and Dermatological Quality Life Index.Results.Forty-one patients were enrolled and qualified for safety analysis. 27 (65.9%) patients experienced at least one AE, of which application-site adverse drug reactions (ADRs) were reported in 6 (14.6%) patients. All ADRs were of grade 1 or 2, most common irritation (4.5%), itching (3.1%), and erythema (2.4%), and resolved during follow-up. The systemic exposure to icotinib was very low; the highest plasma concentration was 0.214 ng/mL, while the area under the curve from 0 to 12 hours was 1.626 h·ng/mL. The TPSS improved for all icotinib groups after treatment in a dose- and time-dependent manner.Conclusion.This phase 1 study demonstrated favorable safety, tolerable toxicity, and preliminary efficacy of icotinib cream in patients with mild to moderate psoriasis. The dose concentration of 2.0% (twice daily based on the fingertip unit method) is recommended for further study.Study Design.This is a single-center, randomized, double-blind, and vehicle-controlled study.

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Randomized, double-blind, vector-controlled study of targeted immunotherapy in patients (pts) with hormone-refractory prostate cancer (HRPC)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.2501 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 2501-2501 ◽

Cited By ~ 10

Author(s):

P. W. Kantoff ◽

L. M. Glode ◽

S. I. Tannenbaum ◽

D. L. Bilhartz ◽

W. G. Pittman ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Scan ◽

Single Case ◽

Phase 1 ◽

Specific Antigen ◽

Safety Data ◽

Data Monitoring Committee ◽

Controlled Study ◽

Double Blind ◽

Gm Csf

2501 Background: Therapeutic vaccines for prostate cancer have yielded encouraging data in uncontrolled Phase 1 and 2 studies. PROSTVAC-VF comprises 2 recombinant viral vectors each containing genes encoding the prostate-specific antigen (PSA) gene modified to optimize antigen presentation in HLA-A2+ pts and 3 T-cell costimulatory molecules (B7.1, LFA3, and ICAM-1 [TRICOM]). These vectors are administered in a heterologous prime-boost regimen with concurrent low-dose GM-CSF to enhance recruitment of antigen-presenting cells to the immunization site. Here we report results of a Phase 2 study in pts with metastatic HRPC. Methods: In this randomized, double-blind, controlled study, pts were randomized 2:1 to receive either PROSTVAC-VF plus GM-CSF or Control (empty vectors plus GM-CSF placebo) for 24 weeks. Eligible pts had rising PSA despite castrate testosterone levels and measurable, asymptomatic or non-narcotic-dependent metastases (positive bone scan or lymph node metastases on abdominal-pelvic CT scan). The primary endpoint is progression-free survival (PFS), with progression defined as appearance of new lesions on bone scan or RECIST-defined progression of nodal metastases. The planned sample size was 120 pts. The study was designed to detect a difference of 38% vs 12% PFS at Week 24 with a 2-sided α of 0.05 and 80% power. An independent Data Monitoring Committee evaluated safety data quarterly. Results: 125 pts were enrolled. Demographics are available for 122 pts (mean age, 73.3 years [range, 52–94]; ∼11% African American). Common adverse events (AEs) in 106 evaluable pts (blinded as of Jan 2006) included immunization site reactions (73%), fatigue (26%), fever (14%), and nausea (13%). The majority were of Grade 1/2 severity. Serious AEs attributed to immunization included 1 thrombotic thrombocytopenic purpura (TTP) event. Conclusions: A large, randomized, controlled study of therapeutic immunization with PROSTVAC-VF in 125 pts with metastatic HRPC has been completed. The therapy is well tolerated and findings are consistent with Phase 1 results, but also included a single case of TTP. Full efficacy data collection is ongoing. [Table: see text]

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FIGHT: A phase 3 randomized, double-blind, placebo controlled study evaluating (bemarituzumab) FPA144 and modified FOLFOX6 (mFOLFOX6) in patients with previously untreated advanced gastric and gastroesophageal cancer with a dose finding phase 1 lead-in.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.tps4135 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. TPS4135-TPS4135 ◽

Cited By ~ 2

Author(s):

Daniel V.T. Catenacci ◽

Peter C. Enzinger ◽

Anteneh A. Tesfaye ◽

Mohamedtaki Abdulaziz Tejani ◽

Janine Powers ◽

...

Keyword(s):

Phase 1 ◽

Dose Finding ◽

Controlled Study ◽

Gastroesophageal Cancer ◽

Phase 3 ◽

Double Blind ◽

Double Blind Placebo ◽

Modified Folfox6

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Platelet Aggregation Analysis of AMG 531 in a Randomized, Placebo-Controlled Study in Healthy Japanese Subjects.

Blood ◽

10.1182/blood.v108.11.1071.1071 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1071-1071

Author(s):

Yuji Kumagai ◽

Tomoe Fujita ◽

Machiko Ozaki ◽

Kunihiko Sahashi ◽

Masayuki Ohkura ◽

...

Keyword(s):

Platelet Count ◽

Platelet Aggregation ◽

Adverse Events ◽

Phase 1 ◽

Subcutaneous Administration ◽

Controlled Study ◽

Limit Of Quantification ◽

Double Blind ◽

Aggregation Analysis ◽

Japanese Subjects

Abstract AMG 531 is a novel thrombopoiesis-stimulating peptibody currently being investigated for the treatment of chronic immune thrombocytopenic purpura. This study was a double-blind, phase 1 evaluation of safety (including a platelet aggregation analysis), pharmacodynamics, and pharmacokinetics of AMG 531 in healthy Japanese men. Thirty subjects were randomly assigned 4:1 (AMG 531:placebo) to each of 3 sequential dose cohorts (0.3, 1, and 2 μg/kg) of 10 subjects each. A single dose of AMG 531 or placebo was administered by subcutaneous injection, and subjects were evaluated for 6 weeks. Concentrations of 0.2 and 2 μg/mL collagen and 0.5 and 2 μmol/L adenosine phosphate were used as reagents in the platelet aggregation analysis conducted on day -1, day 2, day 15, and at the end of the study. No enhancement or reduction in platelet aggregation was detected in samples collected from subjects treated with AMG 531 compared with either pretreatment or placebo samples. Overall, adverse events were similar between the AMG 531 and placebo groups. Treatment-related adverse events (headache, “feeling hot,” migraine without aura, and/or malaise) were reported for 5 of 24 subjects treated with AMG 531. Four of 8 subjects who received the 1 μg/kg dose and 7 of 8 subjects who received the 2 μg/kg dose had platelet count increases ≥ 1.5-fold over baseline, and 3 of 8 subjects who received the 2 μg/kg dose had platelet count increases ≥ 2-fold over baseline, a pharmacodynamic effect similar to that seen in previous studies of non-Japanese subjects. Serum concentrations of AMG 531 were below the lower limit of quantification in all but 2 subjects who received the 2 μg/kg dose. In summary, platelets in subjects treated with AMG 531 functioned normally compared with pretreatment and placebo samples. AMG 531 was generally well tolerated and was effective at raising platelet counts after a single subcutaneous administration.

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