BAROSTIM NEO Hypertension Pivotal Trial
The BAROSTIM NEO Hypertension Trial is a prospective, randomized, controlled trial assessing
the safety and efficacy of the BAROSTIM NEO System in subjects with resistant hypertension.
All subjects are now in long term follow-up and are required to have at least one annual
visit.
Parameters assessed during visits are:
- Office Cuff Blood Pressure
- Physical Assessment
- Subject Medications
- Serious adverse events
A Multicenter, Observational, Open-Label, Single-Arm Study of Tysabri in Early Relapsing-Remitting Multiple Sclerosis in Anti-JCV Antibody Negative Patients
Multiple studies have demonstrated the positive effect of early therapy on patients who were in the earliest stages of relapsing-remitting multiple sclerosis (RRMS; having 1 clinical event clinically isolated syndrome [CIS] and magnetic resonance images [MRIs] suggestive of MS). These studies involved partially effective medications, all with approximately a 30% reduction in relapse rate.Tysabri is a monoclonal antibody that binds and interferes with the action of 41 integrin which results in reducing certain cells of the immune system transmigration across the blood brain barrier.In the recently presented Tysabri Observational Program (TOP) data, early treatment was most effective in treatment-nave patients and patients with lower Expanded Disability Status Scale (EDSS) scores. Thus, use of an effective agent (Tysabri) in the early stages of MS (when immune cell collections have not yet developed behind the blood-brain barrier [BBB]) may be beneficial, and has not been systematically studied.Study population includes RRMS patients diagnosed with Mc Donald's Criteria, Age 18 to 45 years old, Anti-JCV antibody negative test within 6 months of Screening Visit or negative test for anti-JCV antibody at Baseline Visit.Methodology:This is a Phase 4, single-country, multicenter, open-label, prospective, observational study.The primary objective of the study is to determine which baseline and yearly response factors (clinical and para clinical) predict overall disease-free status at Month 12 and Month 24, and clinical disease-free status in subsequent Months 36 and 48. The response factors include clinical assessments of sustained EDSS progression, relapse status, and MRI measures, and patient reported outcomes (PROs) of cognition, capacity to work, quality of life (QoL), and visual function assessments.In general, continuous variables will be presented with summary statistics (mean, standard deviation, median, range), and categorical variables will be presented with frequency distributions. All analyses will be conducted using 2-sided tests at the type I error rate (alpha level) of 0.05 unless otherwise stated.There will be up to 10 clinic visits included in this protocol. A patients participation in the study will last up to 48 months.
An Open-Label, Phase 2 Basket Study of Neratinib in Patients With Solid Tumors With Somatic Activating HER Mutations
This is an open-label, multicenter, multinational, Phase 2 basket study exploring the
efficacy and safety of neratinib as monotherapy or in combination with other therapies in
participants with HER (EGFR, HER2) mutation-positive solid tumors. The study has a basket
design and includes several cohorts, either defined by an actionable somatic mutation or by
actionable mutation and tumor histology, including HER2 mutant breast, HER2 mutant cervical,
HER2 mutant salivary gland, and EGFR Exon 18 mutant Non-small cell lung cancers.
The trial will consist of a screening period, a treatment period, and an end of treatment
visit occurring when neratinib is discontinued for any reason, a safety follow-up visit
occurring 28 days after the last dose of neratinib and a survival follow-up period.
Not recruiting | Any Cancer Condition or Solid Tumor | Multisite
A Randomized Multicenter Pivotal Study of CDX-011 (CR011-vcMMAE)in Patients With Metastatic, gpNMB Over-Expressing, Triple Negative Breast Cancer (The METRIC Study)
CDX-011 consists of an antibody attached to a drug, monomethyl auristatin E (MMAE), that can
kill cancer cells. The antibody delivers the drug to cancer cells by attaching to a protein
called glycoprotein NMB (gpNMB) that is expressed on the cancer cell. The MMAE is then
released inside of the cell, where it interferes with cell growth and may lead to cell death.
This study will examine the efficacy and safety of CDX-011 in patients with advanced TNBC
that makes the gpNMB protein. The effect of CDX-011 will be compared to treatment with
capecitabine.
Eligible patients who enroll in the study will be randomly assigned (by chance) to receive
treatment with CDX-011 or with capecitabine. For every three patients enrolled, two will
receive CDX-011 and one will receive treatment with capecitabine. All patients enrolled in
the study will be closely monitored to determine if their cancer is responding to treatment
and for any side effects that may occur.
A Study of HSP90 Inhibitor AT13387 Alone and in Combination With Crizotinib in the Treatment of Non-small Cell Lung Cancer (NSCLC)
This is a 3-part phase 1-2 study in patients with anaplastic lymphoma kinase (ALK) + or other
potentially crizotinib-sensitive NSCLC who have been receiving crizotinib. Part A is a
single-arm, Phase 1, open-label, dose escalation design in patients with NSCLC who have
already been receiving crizotinib for at least 8 weeks and continue to tolerate therapy. Part
B is a Phase 2, open-label, randomized continuation design comparing crizotinib alone versus
the combination of crizotinib + AT13387 at the maximum tolerated dose established in Part A.
Part C is an open-label, randomized, Phase 2, Simon's 2 stage design evaluating single agent
AT13387 or combination AT13387 + crizotinib at the MTD established in Part A in patients who
progressed on crizotinib at any time.
Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4 Study)
The A4 study is a clinical trial for older individuals who have evidence of amyloid plaque
build-up in their brains who may be at risk for memory loss and cognitive decline due to
Alzheimer's disease. The A4 study will test an anti-amyloid investigational drug in older
individuals who do not yet show symptoms of Alzheimer's disease cognitive impairment or
dementia with the aim of slowing memory and cognitive decline. The A4 study will also test
whether anti-amyloid treatment can delay the progression of AD related brain injury on
imaging and other biomarkers.
Phase II Randomized Trial of ABT-888 in Combination With Metronomic Oral Cyclophosphamide in Refractory BRCA-Positive Ovarian, Primary Peritoneal, Ovarian High-Grade Serous Carcinoma, Fallopian Tube Cancer, or Triple-Negative Breast Cancer
Background:
- The poly (ADP-ribose) polymerase (PARP) family of enzymes is critical for maintaining
genomic stability by regulating a variety of DNA repair mechanisms.
- Individuals with deleterious mutations in the BRCA1 or BRCA2 tumor suppressor genes have
an increased risk of developing breast and ovarian cancers due to impaired or defective
DNA damage repair; these individuals have an increased susceptibility to DNA-damaging
agents and PARP inhibitors. Inhibition of PARP inhibits the repair of DNA damage caused
by alkylating agents such as cyclophosphamide.
- Metronomic cyclophosphamide has demonstrated efficacy in several tumor types. The PARP
inhibitor ABT-888 has been shown to potentiate the action of cyclophosphamide in
xenograft models. This combination is well tolerated in a Phase I study and showing
promising activity.
Objectives:
- Compare the response rate (complete response (CR) + partial response (PR)) of the
combination of ABT-888 with metronomic oral cyclophosphamide to the response rate
(CR+PR) of metronomic oral cyclophosphamide in patients with deleterious BRCA mutations
and refractory ovarian cancer or patients with primary peritoneal or ovarian high-grade
serous carcinoma or fallopian tube cancer.
- Compare the response rate (CR+PR) of the combination of ABT-888 with metronomic oral
cyclophosphamide to the response rate (CR+PR) of single-agent oral cyclophosphamide in
patients with triple-negative metastatic breast cancer, stratified for deleterious BRCA
mutation.
- Compare the response rate (CR+PR) of the combination of ABT-888 with metronomic oral
cyclophosphamide to the response rate (CR+PR) of single-agent metronomic oral
cyclophosphamide in patients with refractory low-grade lymphomas.
Secondary Objectives:
- Determine PAR levels in tumor biopsies, evaluate in archival tissue whether patients tumors
have mutations in genes involved in DNA damage repair (e.g., BRCA/Fanconi anemia/protein 53
(p53)), perform exploratory gene expression profiling to correlate PARP messenger ribonucleic
acid (mRNA) levels or BRCA mutation status with response to therapy, count circulating tumor
cells (CTCs), and determine H2AX levels in CTCs and tumor biopsies (National Cancer Institute
(NCI) clinical center only).
Eligibility:
-Adults with refractory BRCA-positive ovarian cancer, primary peritoneal or ovarian
high-grade serous carcinoma, fallopian tube cancer, triple-negative breast cancer, or
low-grade lymphoid malignancies (non-Hodgkin's lymphoma) whose disease has progressed
following at least one line of therapy.
Study Design:
- This is a randomized, multi-histology Phase II trial with patients enrolled into 3
cohorts: BRCA-positive ovarian cancer or primary peritoneal or ovarian high-grade serous
carcinoma or fallopian tube cancer (A); triple-negative breast cancer (B); or low grade
non-Hodgkin's lymphoma (C). Patients in cohort A will be randomized to the combination
of ABT-888 with metronomic oral cyclophosphamide or metronomic oral cyclophosphamide
alone. Patients in cohort B will be randomized to the combination of ABT-888 with
metronomic oral cyclophosphamide or metronomic oral cyclophosphamide alone. Patients in
cohort C will be randomized to the combination of ABT-888 with metronomic oral
cyclophosphamide or metronomic oral cyclophosphamide alone.
- Cyclophosphamide (50 mg) and ABT-888 (60 mg) will be administered orally once a day,
continuously in 21-day cycles.
An Open Label Multicentre Phase 1 Study of Oral IGF-1R Inhibitor PL225B in Subjects With Advanced Refractory Solid Tumors.
An open label multicentre Phase 1 study of oral IGF-1R inhibitor PL225B in subjects with
advanced refractory solid tumors. This is a dose-finding trial using the modified Accelerated
Titration Design with 3 new subjects per cohort and 100% dose increments in the accelerated
phase followed by standard phase with 40% dose increments.Subjects will receive study drug on
a daily basis for twenty-one (21) days according to the dose and schedule specified for a
particular cohort of therapy. Toxicity profile of the drug will be assessed during Cycle 1 of
subject treatment in each cohort for determination of Maximum Tolerated Dose (MTD) according
to the schedule given below.
Not recruiting | Any Cancer Condition or Solid Tumor | Multisite
Portico Re-sheathable Transcatheter Aortic Valve System US IDE Trial
The PORTICO pivotal IDE trial will include a randomized cohort of 750 subjects enrolled at up
to 70 investigational sites in the United States and Australia. Patients will be randomized
(1:1) to receive the SJM Portico Transcatheter Heart Valve and Delivery Systems (Portico) or
any FDA-approved, commercially-available Transcatheter Aortic Valve Replacement (TAVR)
System. The randomized cohort will be tested for two co-primary endpoints at 30 days (primary
safety endpoint) and 1 year (primary effectiveness endpoint). At the time of the primary
randomized cohort analysis, the risk cohorts will be combined and analysis will be conducted
on the intention-to-treat (n=750) population.
The FlexNav Delivery System study will be conducted as a separate arm of the PORTICO IDE
trial and will include up to 200 high or extreme risk subjects; including a minimum of 100
analysis subjects. The study will characterize the safety of the next-generation Portico
Delivery System ("FlexNav™ Delivery System"). The primary analysis cohort will include
FlexNav analysis subjects.
The IDE Valve-in-Valve registry will enroll up to 100 high or extreme risk subjects with a
failed surgical bioprosthesis who are eligible to receive a Portico Transcatheter Heart
Valve.
All subjects enrolled in the PORTICO pivotal IDE trial will undergo follow-up at baseline,
peri- and post-procedure, at discharge or 7 days post-procedure (whichever comes first), 30
days, 6 months, 12-months and then annually through 5-years.
A Multi-Center, Randomized, Prospective, Open-Label Phase III Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Hepatitis C Immune Globulin Intravenous (Human), Civacir, in Orthotopic Liver Transplant Recipients
End stage liver disease secondary to Hepatitis C virus infection is the most frequent indication for liver transplantation. However, recurrence of the disease is almost universal and is the cause of increased morbidity and mortality. At this time, attempts to treat recurrence have been difficult as the treatment is difficult to tolerate and often ineffective in the post transplant setting. In this study, we hope to learn if treatment with hepatitis C immunoglobulin (Civacir) post-operatively is safe and effective in the prevention of disease recurrence. Participants will be randomized 1:1 to 300mg/kg or control. Participants will be followed out to 6 months with monitoring of hepatic function and HCV levels. Safety data will be collected through medical follow up, examinations and follow up of hepatic function. Statistical analysis will be conducted by the sponsor to determine if the drug (and dose) are effective in preventing recurrent HCV.
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