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TRIAL NAME: Phase III - CERTAIN-1 (GT-1) (Japan); BRIEF: The purpose of this phase 3, multicenter study is to evaluate the efficacy and safety of ABT-493/ABT-530 in Japanese adults with chronic Hepatitis C Virus (HCV)-infected, HCV direct-acting antiviral agent (DAA) treatment-naïve, and DAA treatment-experienced Japanese adult subjects. ; DRUG USED: Mavyret; DRUG CLASS: New Molecular Entity (NME); INDICATION: Hepatitis C (HCV) (Antiviral); TARGET: HCV Protease, Non-structural 5A protein (NS5A); THERAPY: Combination; LEAD SPONSOR: AbbVie; CRITERIA: Inclusion Criteria: - Females were postmenopausal for at least 2 years; surgically sterile or had a vasectomized partner; or, if of childbearing potential and sexually active with a male partner, were currently using at least 1 effective method of birth control at the time of Screening and agreed to practice 1 effective method of birth control from Screening through 30 days after stopping study drug. Sexually active males were surgically sterile or, if sexually active with a female partner of childbearing potential, agreed to practice 1 effective form of birth control from Screening through 30 days after stopping study drug. - Screening central laboratory result indicated HCV single genotype infection for the appropriate treatment arm, without co-infection of any other genotype. - Chronic HCV infection is defined as one of the following: - Positive for anti-HCV antibody (Ab) and/or HCV RNA at least 6 months before Screening. - A liver biopsy consistent with chronic HCV infection. - Agreed to voluntarily sign and date an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) prior to the initiation of any screening or study specific procedures. - Participants who were able to understand and adhere to the study visit schedule and all other protocol requirements. - Absence of hepatocellular carcinoma (HCC) as indicated by an ultrasound, computed tomography (CT) scan or magnetic resonance imaging (MRI). Exclusion Criteria: - Females who were pregnant or planned to become pregnant, or breastfeeding or males whose partner was pregnant or planning to become pregnant during the study. - Participants co-infected with hepatitis B virus or human immunodeficiency virus. - Use of contraindicated medications or supplements within 2 weeks or 10 half-lives (if known), whichever was longer, prior to the first dose of any study drug. - Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol in the opinion of the investigator. - Any cause of liver disease other than chronic HCV infection. - Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of decompensated liver disease. - Consideration by the investigator, for any reason, that the participant is an unsuitable candidate to receive ABT-493/ABT-530. ; PRIMARY OUTCOME: Percentage of Participants in Arms A and B With Sustained Virologic Response 12 Weeks Post-treatment (SVR12); SECONDARY OUTCOME 1: Percentage of Participants in Arm A With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)

Yes

TRIAL NAME: Phase III - SUNRISE 2; BRIEF: The key objectives of this study are to determine, using sleep diaries, whether lemborexant at the doses 5 milligrams (mg) and 10 mg is superior to placebo on subjective sleep onset, subjective sleep efficiency, and subjective sleep maintenance in participants with insomnia disorder. ; DRUG USED: Dayvigo; DRUG CLASS: New Molecular Entity (NME); INDICATION: Insomnia; TARGET: Hypocretin/orexin receptor ; THERAPY: Monotherapy; LEAD SPONSOR: Eisai Inc.; CRITERIA: Inclusion Criteria: - Male or female, age 18 years or older at the time of informed consent - Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) criteria for Insomnia Disorder, as follows: - Complains of dissatisfaction with nighttime sleep in the form of difficulty getting to sleep, difficulty staying asleep, and/or awakening earlier in the morning than desired despite adequate opportunity for sleep - Frequency of complaint ≥3 times per week - Duration of complaint ≥3 months - Associated with complaint of daytime impairment - History of (Subjective Sleep Onset Latency) sSOL ≥30 minutes on at least 3 nights per week in the previous 4 weeks and/or subjective Wake after Sleep Onset (sWASO) ≥60 minutes on at least 3 nights per week in the previous 4 weeks - History of regular time spent in bed, either sleeping or trying to sleep, between 7 and 9 hours - Regular bedtime, between 21:00 and 01:00 and regular wake time, the time the participant gets out of bed for the day, between 05:00 and 10:00 - Insomnia Severity Index (ISI) score ≥15 - Confirmation of current insomnia symptoms as determined from the Sleep Diary completed on at least 7 consecutive mornings (minimum 5 of 7 for eligibility), such that sSOL ≥30 minutes on at least 3 of the 7 nights and/or sWASO ≥60 minutes on at least 3 of the 7 nights - Confirmation of time spent in bed, as determined from on the Sleep Diary completed on 7 mornings between the first and second screening visit, such that there are not more than 2 nights with duration of time spent in bed 7 hours and 10 hours - Confirmation of regular bedtimes and wake times such that the participant has a regular time spent in bed, either sleeping or trying to sleep, between 7 and 10 hours for the final 7 nights of the before visit 3. - Confirmation of regular bedtime between 21:00 and 01:00 and time of getting out of bed for the day between 05:00 and 10:00 for the final 7 nights of the before visit 3. - Willing and able to comply with all aspects of the protocol, including staying in bed for at least 7 hours each night - Willing to not start a behavioral or other treatment program for insomnia during the participants participation in the study Exclusion Criteria: - A current diagnosis of sleep-related breathing disorder, periodic limb movement disorder, restless legs syndrome, circadian rhythm sleep disorder, or an exclusionary score on screening instruments to rule out individuals with symptoms of certain sleep disorders other than insomnia. - STOPBang score greater than or equal to (>=) 5 - International Restless Legs Scale (IRLS) score >=16 - Epworth Sleepiness Scale (ESS) score >15 - Reports symptoms potentially related to narcolepsy that in the clinical opinion of the investigator indicates the need for referral for a diagnostic evaluation for the presence of narcolepsy - Reports a history of sleep-related violent behavior, or sleep driving, or any other complex sleep-related behavior, eg, making phone calls, or preparing and eating food while asleep - For participants who underwent polysomnography (PSG) within the previous year: - Age 18 to 64 years: Apnea Hypopnea Index ≥10, or Periodic Limb Movements with Arousal Index ≥10 - Age ≥65 years: Apnea Hypopnea Index >15, or Periodic Limb Movements with Arousal Index >15 - Beck Depression Inventory - II (BDI II) score >19 at Screening - Beck Anxiety Inventory (BAI) score >15 at Screening - Habitually naps more than 3 times per week - Females who are breastfeeding or pregnant at Screening or Study Baseline - Females of childbearing potential who are not practicing acceptable pregnancy prevention methods (NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal or have been sterilized surgically.) - Excessive caffeine use that in the opinion of the investigator contributes to the participant's insomnia, or habitually consumes caffeine-containing beverages after 18:00 and is unwilling to forego caffeine after 18:00 for the duration of his/her participation in the study - History of drug or alcohol dependency or abuse within approximately the previous 2 years - Reports habitually consuming more than 14 drinks containing alcohol per week (females) or more than 21 drinks containing alcohol per week (males), or unwilling to limit alcohol intake to no more than 2 drinks per day or forego having alcohol within the 3 hours before bedtime for the duration of his/her participation in the study - A prolonged QT/QT interval corrected by Fridericia's formula (QTcF >450 ms) as demonstrated by a repeated electro cardiogram(ECG) at Screening (repeated only if initial ECG indicates a QTcF interval >450 ms) - Current evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal, neurological [including participants who lack capacity and/or whose cognitive decline indicates disorientation to person/place/time and/or situation], or psychiatric disease or malignancy other than basal cell carcinoma) or chronic pain that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments - Comorbid nocturia resulting in frequent need to get out of bed to use the bathroom during the night - Scheduled for major surgery during the study - Used any prohibited prescription or over-the-counter concomitant medications within 1 week before the first dose of study medication - Used any modality of treatment for insomnia, including cognitive behavioral therapy or marijuana within 2 weeks before Screening - Failed treatment with suvorexant (Belsomra®) (efficacy and/or safety) following treatment with an appropriate dose and of adequate duration in the opinion of the investigator - Transmeridian travel across more than 3 time zones in the 2 weeks before Screening, or between Screening and Study Baseline - Previously participated in any clinical trial of lemborexant ; PRIMARY OUTCOME: Change From Baseline in Subjective Sleep Onset Latency (sSOL) at Month 6; SECONDARY OUTCOME 1: Change From Baseline in sSOL at the Beginning of Treatment (Mean of the 7 Nights After the First Dose in Placebo-Controlled Period), and at Months 1 and 3

Yes

TRIAL NAME: Phase I - SAD (Healthy Volunteers); BRIEF: The purpose of this study is to investigate the safety and tolerability of JNJ-54175446 versus placebo after single oral dose administration (ascending dose levels), to determine the maximal tolerated dose (MTD) or the safety and tolerability at exposures resulting in full target engagement for at least 24 hours in all participants (whichever comes first), to characterize the pharmacokinetics of JNJ-54175446 in plasma, cerebrospinal fluid (CSF) and urine and to investigate the effect of food (high fat/high calorie) on the pharmacokinetics of JNJ 54175446 after single oral dose administration. ; DRUG USED: JNJ-54175446; DRUG CLASS: New Molecular Entity (NME); INDICATION: Major Depressive Disorder (MDD); TARGET: P2X7 Receptor; THERAPY: Monotherapy; LEAD SPONSOR: Janssen-Cilag International NV; CRITERIA: Inclusion Criteria: - Participants must have a body mass index (BMI) between 18 and 32 kg/m^2, inclusive (BMI = weight/height^2) - Participants must be healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel[excluding liver function tests], hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities to be not clinically significant. This determination must be recorded in the subject's source documents and initialed by the investigator - A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug. In addition, their female partner should also use an appropriate method of birth control for at least the same duration For Part 1 and 3: - Healthy male participants between 18 and 54 years of age, inclusive For Part 2: - Healthy male or female participants between 55 and 75 years of age, inclusive - Participant must be healthy on the basis of both physical and neurological examination performed at screening and at admission to the clinical unit - Women must not be of childbearing potential (i.e., must be postmenopausal with amenorrhea for at least 12 months); permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy); or otherwise be incapable of pregnancy Exclusion Criteria: - Participant has a history of or current liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic (including coagulation disorders), rheumatologic, psychiatric, or metabolic disturbances, any inflammatory illness or any other illness that the Investigator considers should exclude the participant - Participant has any liver function test (including alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyltransferase [gamma-GT], alkaline phosphatase [ALP] and bilirubin) at screening exceeding the upper limit of normal - Participant has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening - Participant has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening - Participant has a Prothrombin time [PT] >14 seconds and/or an activated partial thromboplastin time [aPTT] >35 seconds ; PRIMARY OUTCOME: Number of Participants with Adverse Events; SECONDARY OUTCOME 1:

Yes

TRIAL NAME: Phase IIIb/IV - PHYSACTO; BRIEF: The primary objectives of the study are to explore the effect of treatment with orally inhaled tiotropium + olodaterol fixed dose combination with and without exercise training, and tiotropium comparing to placebo, on top of behavioural modification in improving exercise capacity in patients with COPD ; DRUG USED: Stiolto Respimat; DRUG CLASS: New Molecular Entity (NME); INDICATION: Chronic Obstructive Pulmonary Disease (COPD); TARGET: Beta Adrenergic Receptors, Muscarinic acetylcholine receptor; THERAPY: Monotherapy and Combo Therapy; LEAD SPONSOR: Boehringer Ingelheim; CRITERIA: Inclusion criteria: - All patients must sign an informed consent consistent with International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) - Good Clinical Practice (GCP) guidelines prior to participation in the trial, which includes medication washout and restrictions. - All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria: Patients must have relatively stable airway obstruction with a post-bronchodilator forced expiratory volume in one second >=30% and <80% of predicted normal; Global Initiative for Chronic Obstructive Lung Disease grade II - III, and a post-bronchodilator Tiffeneau index <70% at Visit 1. - Male or female patients, aged >=40 years and <=75 years. - Patients must be current or ex-smokers with a smoking history of more than 10 pack years. Patients who have never smoked cigarettes must be excluded. Exclusion criteria: - Patients with a significant disease other than chronic obstructive pulmonary disease. - Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis. - Patients with a history of asthma. - A diagnosis of thyrotoxicosis. - A diagnosis of paroxysmal tachycardia (>100 beats per minute). - A history of myocardial infarction within 1 year of screening visit. - Unstable or life-threatening cardiac arrhythmia. - Hospitalized for heart failure within the past year. - Known active tuberculosis. - A malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years. - A history of life-threatening pulmonary obstruction and patients with chronic respiratory failure. - A history of cystic fibrosis. - Clinically evident bronchiectasis. - A history of significant alcohol or drug abuse. - Any contraindications for exercise testing. - Patients who have undergone thoracotomy with pulmonary resection. - Patients being treated with any oral ß-adrenergics. - Patients being treated with oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day. - Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigators opinion will be unable to abstain from the use of oxygen therapy during clinic visits. - Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit or patients who are currently in a pulmonary rehabilitation program. - Patients who have a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnoea, such as arthritis in the leg, angina pectoris or claudication or morbid obesity. - Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to screening visit. - Patients with known hypersensitivity to ß-adrenergics drugs, anticholinergic drugs, benzalkonium chloride, disodium edentat, or any other component of the Respimat® inhalation solution delivery system. - Pregnant or nursing women. - Women of childbearing potential not using highly effective methods of birth control. - Patients who have previously been randomized in this study or are currently participating in another study. ; PRIMARY OUTCOME: Endurance Time During Endurance Shuttle Walk Test (ESWT) to Symptom Limitation After 8 Weeks; SECONDARY OUTCOME 1: Average Daily Walking Time Measured by the Activity Monitor in the Week Prior to Week 12

Yes

TRIAL NAME: Phase I/II - Dose Selection; BRIEF: The current understanding of PR104 justifies the evaluation of PR104 in subjects with relapsed/refractory AML and ALL. These include: - Hypoxia. Leukemic bone marrow is likely to demonstrate a level of hypoxia sufficient to activate PR104 to its active metabolites PR104H and PR104M. - Myelotoxicity as the primary toxicity at MTD. In prior clinical studies in subjects with solid tumors PR104 has demonstrated myelotoxicity as the primary toxicity. This observation suggests that PR104 will exert a similar effect on leukemic cells. - AKR1C3. AML has been reported to exhibit high levels of AKR1C3 which should lead to selective activation of PR104 within both hypoxic and oxic leukemic cells. - Preclinical data. PR104 has demonstrated impressive activity in an initial study using primary human ALL in a mouse model. The initial dose finding phase of the study will provide estimates of the activity and toxicity of PR104 in subjects with refractory/relapsed AML, and determine the optimal individualized dose to give each subject based on his/her covariates (prior CR duration, prior number of salvage therapies, age). Once a potentially beneficial dose has been determined, an expanded cohort of subjects with AML or ALL will receive PR104 at a uniform dose. This information will prove valuable in defining the future clinical development of PR104, and in determining if PR104 has sufficient activity and acceptable safety in AML to warrant future phase II or phase III studies in this indication. Primary objectives - Determine the toxicities and recommended dose of PR104 when administered IV to subjects with relapsed/refractory AML and ALL. Secondary objectives - Evaluate the pharmacokinetics (PK) of PR104 and a series of PR104 metabolites - Evaluate any anti-tumor effects of PR104 - Evaluate the expression of AKR1C3 in bone marrow and leukemic cells - Evaluate potential biomarkers of hypoxia ; DRUG USED: PR104; DRUG CLASS: New Molecular Entity (NME); INDICATION: Acute Myelogenous Leukemia (AML); TARGET: DNA; THERAPY: Monotherapy; LEAD SPONSOR: Proacta, Incorporated; CRITERIA: Inclusion Criteria: - Signed informed consent - Age 18 years or more - Histologically diagnosed acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) by WHO classification - Refractory or relapsed disease (requiring at least 5% leukemic blasts in the bone marrow, regardless of the presence of other features such as new or recurrent dysplastic changes or extramedullary disease) according to the following definitions: AML Relapsed (defined as ≥5% leukemic blasts in the bone marrow) after receiving up to 2 prior induction regimens, (i.e., first or second relapse); Refractory (defined as ≥5% leukemic blasts in the bone marrow) to not more than 1 prior induction regimen (defined as failure to achieve a CR or CRp following induction therapy), (i.e., up to 1 induction failure). ALL Relapsed/refractory (defined as ≥5% leukemic blasts in the bone marrow) after receiving 1 or more prior induction regimens, (i.e., any number of relapses) - ECOG performance status of 0-2 - At least 2 weeks from administration of prior anti-leukemia therapy unless subject has progressed while receiving targeted therapy on a continuous dosing schedule - No remaining clinically significant toxicities from prior chemotherapy of grade 2 or greater - Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must be willing to use an acceptable contraceptive method (abstinence, oral contraceptive or double barrier device) for the duration of the study and for 30 days following the last dose of study drug, and must have a negative urine or serum pregnancy test within 2 weeks prior to beginning treatment on this trial - Sexually active men must be willing to use an acceptable contraceptive method for the duration of time on study and for 30 days following the last dose of study drug - Clinical laboratory values within the following ranges unless considered due to leukemic organ involvement: Serum creatinine 2.0 mg/dl; Total bilirubin 1.5x the upper limit of normal unless considered due to Gilbert's syndrome; Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) 3x the upper limit of normal - Willingness to provide at least one pre-PR104 leukemia sample (e.g., bone marrow or peripheral blood) for analysis of AKR1C3. Exclusion Criteria: - Pregnant and nursing subjects - Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, or uncontrolled congestive heart failure - Another active concomitant malignancy likely to effect any of the primary or secondary outcome measures in the current study - Subjects receiving any other standard or investigational treatment for their hematologic malignancy (other than hydroxyurea). Subjects with CNS leukemia are eligible and may receive concurrent standard intrathecal chemotherapy. ; PRIMARY OUTCOME: Determine the optimal individualized dose to give each refractory/relapsed AML subject based on his/her covariates (prior CR duration, prior number of salvage therapies, age).; SECONDARY OUTCOME 1:

No

TRIAL NAME: Phase IIa - NewPLACE; BRIEF: This 2-arm, multi-center, open-label, parallel-group phase II trial will assess the efficacy, safety and pharmacokinetics/pharmacodynamics of the human antibody MOR202 in subjects with anti-PLA2R antibody-positive membranous nephropathy indicated for immunosuppressive therapy ; DRUG USED: Felzartamab; DRUG CLASS: Biologic; INDICATION: Autoimmune Disorders; TARGET: Cluster of Differentiation 38 (CD38); THERAPY: Monotherapy; LEAD SPONSOR: HI-Bio; CRITERIA: Inclusion Criteria: - Subjects > 18 to < 80 years (at date of signing the informed consent form [ICF]). - Urine protein to creatinine ratio (UPCR) of > 3.0 g/g or proteinuria > 3.5 g/24 h - Estimated glomerular filtration rate (eGFR) > 50 ml/min/1.73 m² (eGFR >30 and < 50 ml/min/1.73 m² can be included provided an interstitial fibrosis and tubular atrophy (IFTA) score of < 25% in a kidney biopsy) - Not in spontaneous remission despite proper treatment with angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs) (sufficient dose and treatment duration) as per clinical practice and scientific guidelines. If the subject is intolerant to ACEI and ARBs, the reason must be documented and approval for enrollment be obtained from the Medical Monitor. - Systolic blood pressure (BP) <150 mmHg and diastolic BP <100 mmHg after 5 minutes of rest. - Serum anti-PLA2R antibodies > 50.0 RU/mL determined by Euroimmun ELISA. - Female subjects: A female is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: 1. Not a female of childbearing potential (FCBP) 2. A FCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 3 months after the last dose of MOR202 Key Exclusion Criteria: - Hemoglobin < 80 g/L. - Thrombocytopenia: Platelets < 100.0 x 109/L. - Neutropenia: Neutrophils < 1.5 x 109/L. - Leukopenia: Leukocytes < 3.0 x 109/L. - Hypogammaglobulinemia: Serum immunoglobulins ≤ 4.0 g/L. Subjects may receive supportive therapies to meet the above criteria - B-cells < 5 x 106/L - Diabetes mellitus type 2: Subjects with type 2 diabetes mellitus may only enter the clinical trial if a kidney biopsy performed within 6 months prior to screening shows MN without evidence of diabetic nephropathy and diabetes is controlled, as shown by: 1. Glycated hemoglobin (HbAlc) <8.0 % or 64 mmol/mol. 2. No diabetic retinopathy known. 3. No peripheral neuropathy known. - Total bilirubin, aspartate aminotransferase or alanine aminotransferase >1.5 x ULN, alkaline phosphatase >3.0 x ULN. ; PRIMARY OUTCOME: efficacy: percent change of anti-PLA2R antibody levels; SECONDARY OUTCOME 1: efficacy: immunological complete response (ICR) rate

No

TRIAL NAME: Phase III - CLARITY-3; BRIEF: ; DRUG USED: Nuplazid; DRUG CLASS: New Molecular Entity (NME); INDICATION: Major Depressive Disorder (MDD); TARGET: Serotonin 5-HT2A receptor; THERAPY: Monotherapy; LEAD SPONSOR: ; CRITERIA: ; PRIMARY OUTCOME: ; SECONDARY OUTCOME 1:

No

TRIAL NAME: Phase II - FALKON; BRIEF: Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by the presence of bone in soft tissue where bone normally does not exist, known as Heterotopic Ossification (HO). It is often associated with painful, recurrent episodes of soft tissue swelling (flare-ups) that lead to abnormal stiffening and immobility (ankyloses) of major joints with cumulative and irreversible loss of movement and disability. This study will evaluate the efficacy of 2 dosing regimens of IPN60130 in inhibiting new HO volume compared with placebo (a dummy treatment) in adult and paediatric participants with FOP. It will be assessed by a scan (provides internal images of the body) called low dose Whole Body Computed Tomography (WBCT), excluding head. Adults and participants 5 years of age or older are also eligible for a sub study to evaluate HO lesions assessed by another type of scan, Fluorine-18-labelled natrium fluoride Positron Emission Tomography-Computed Tomography ([18F]NaF PET-CT ). ; DRUG USED: IPN60130; DRUG CLASS: New Molecular Entity (NME); INDICATION: Fibrodysplasia Ossificans Progressiva (FOP); TARGET: ALK-2 (activin receptor-like kinase-2)/Activin A receptor, type I (ACVR1); THERAPY: Monotherapy; LEAD SPONSOR: Clementia Pharmaceuticals Inc.; CRITERIA: Key Inclusion Criteria: - Participants must be at least 5 years of age, to be confirmed (entry for younger paediatric participants <15 years of age will only be once safety in adult and older paediatric participants ≥15 years of age has been established) at the time of signing the informed participant/parent consent and, for participants who are minors, age-appropriate assent. - Participants must be at least 15 years of age at the time of signing the informed participant/parent consent for the main study and, for participants who are minors, age-appropriate assent - Participants must be clinically diagnosed with FOP, with the R206H ACVR1 mutation or other FOP variants associated with progressive HO. - Participants must have disease progression in the preceding year of the screening visit. - Participants who have participated in a prior clinical study using another investigational product for the treatment of FOP may be enrolled after a washout of at least 5 half-lives of the other investigational product. Participants with prior treatment such as, but not limited to, imatinib, isotretinoin, garetosmab, or palovarotene may be enrolled 30 days after discontinuation or after washout of at least 5 half-lives, whichever is longer. 1. Washout period for palovarotene is 30 days 2. Washout period for garetosmab is 4 months - Participants must be able to perform pulmonary function tests adequately and reliably. - Participants must be able to have an adequate echocardiography assessment at screening for evaluation of left ventricular structure and function as defined by the protocol. - Participants must be accessible for treatment and follow-up and be able to undergo all study procedures. Participants living at distant locations from the investigational site must be able and willing to travel to a site for the initial and all on-site follow-up visits. Participants must be able to undergo low-dose WBCT (excluding head) without sedation. - Body weight ≥10 kg. - Abstinent or using two highly effective forms of birth control. Females must also have a negative blood or urine pregnancy test prior to administration of study drug. - Participants must be capable of giving written, signed, and dated informed participant/parent consent; and for participants who are minors, age-appropriate assent and/or legal guardian consent (performed according to local regulations) Key Exclusion Criteria: - Participants with complete heart block and left bundle branch block on screening electrocardiogram. - Participants with screening echocardiography showing septal or left ventricular free wall thickness >12 mm for adult participants or a z-score >3 compared with population norms for children and adolescent participants or left ventricular ejection fraction (LVEF) <50%. - Participants with severe mitral or tricuspid regurgitation on echocardiography at screening. - Participants with significant underlying lung disease requiring supplementary oxygen or forced vital capacity <35% of predicted at screening. - Participants with uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric, or another significant disease as judged by the investigator. - Participants with severe hepatic impairment. - Concomitant medications that are strong inhibitors (including grapefruit juice) or inducers (including St John's Wort) of cytochrome P450 (CYP) 3A4 activity; or kinase inhibitors such as imatinib. - Prior use in the past year and concomitant use of bisphosphonates for participants in the PET-CT sub study. - Concurrent participation in another interventional clinical study, or a noninterventional study with radiographic measures or invasive procedures (e.g. collection of blood or tissue samples). - Amylase or lipase >2× the upper limit of normal (ULN) or with a history of chronic pancreatitis. - Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5×ULN. - Participants with hematologic abnormalities: - Hgb<10g/dL - Platelets<75,000/mm3 - WBC<2000/mm3 - Participants with coagulation test measurements outside of the normal range at screening. ; PRIMARY OUTCOME: Annualized change in HO volume as assessed by low-dose WBCT (excluding the head) in treated participants receiving IPN60130 compared with placebo.; SECONDARY OUTCOME 1: Change in HO volume of new HO lesions as detected by WBCT in participants receiving IPN60130 compared with placebo recipients

No

TRIAL NAME: Phase II - COMPARE (vs. Krystexxa); BRIEF: This is a randomized, parallel-arm, multicenter study to compare the safety and efficacy profiles of SEL-212 and KRYSTEXXA®. Participants will be randomized 1:1 to receive treatment with SEL-212 or KRYSTEXXA® for 6 months. Efficacy assessments, as measured by serum uric acid (SUA) levels, will be conducted at intervals that are appropriate to determine treatment effect differences. Safety will be monitored throughout the study. ; DRUG USED: SEL-212; DRUG CLASS: Biologic; INDICATION: Gout; TARGET: Uric Acid; THERAPY: Combination; LEAD SPONSOR: Selecta Biosciences, Inc.; CRITERIA: Key Inclusion Criteria: 1. History of symptomatic gout defined as: 1. ≥ 3 gout flares within 18 months of Screening or 2. Presence of ≥ 1 tophus or 3. Current diagnosis of gouty arthritis 2. At the Screening Visit: male age 21 - 80 years, inclusive, or female of non-childbearing potential age 21-80 years, inclusive, where non-childbearing potential is defined as: 1. > 6 weeks after hysterectomy with or without surgical bilateral salpingooperhectony or 2. Post-menopausal (> 24 months of natural amenorrhea) 3. Has at the Screening Visit SUA ≥ 7 mg/dL, with chronic refractory gout defined as having failed to normalize SUA and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the medically appropriate dose or for whom these drugs are contraindicated; 4. Willing to provide written informed consent prior to the conduct of any study specific procedures; 5. Understands and is willing and able to comply with study requirements, including the schedule of follow-up visits Key Exclusion Criteria: 1. Prior exposure to any experimental or marketed uricase (e.g., pegloticase [Krystexxa®], pegadricase [SEL-037], rasburicase [Elitek, Fasturtec]); 2. History of anaphylaxis or severe allergic reactions to medications; 3. History of any allergy to pegylated products 4. Drugs known to interact with Rapamune cannot be used during the trial; 5. Uncontrolled diabetes; 6. Glucose-6-phosphate dehydrogenase (G6PD) deficiency; 7. Uncontrolled hypertension; 8. Participants whose arrhythmia is unstable on current treatment; 9. History of coronary artery disease, including myocardial infarction or unstable angina, within the last 6 months; 10. Congestive heart failure; 11. History of hematological disorders within 1 year or autoimmune disorders, is immunosuppressed or immunocompromised; 12. Has received an inactivated vaccine in the previous 3 months or has received a live virus vaccine in the previous 6 months; 13. Is planning to receive any vaccination or live virus vaccination during the study; ; PRIMARY OUTCOME: Number of Participants With Serum Uric Acid (SUA) Reduction of < 6 mg/dL for at Least 80% of the Time; SECONDARY OUTCOME 1: Number of Participants With SUA Reduction of < 6 mg/dL for At Least 80% of the Time During Month 6

Yes

TRIAL NAME: Phase IIIb - DUAL IX; BRIEF: This trial is conducted globally. The aim of this trial is comparing glycaemic control and safety of insulin degludec/liraglutide (IDegLira) versus insulin glargine (IGlar) as add-on therapy to SGLT2i (sodium-glucose cotransporter 2 inhibitors) in subjects with type 2 diabetes mellitus. ; DRUG USED: Xultophy; DRUG CLASS: Non-NME; INDICATION: Diabetes Mellitus, Type II; TARGET: GLP-1 Receptor, Insulin Receptor; THERAPY: Combination; LEAD SPONSOR: Novo Nordisk A/S; CRITERIA: Inclusion Criteria: - Male or female, age at least 18 years at the time of signing informed consent - Subjects diagnosed (clinically) with type 2 diabetes mellitus - HbA1c 7.0-11.0% [53-97 mmol/mol] (both inclusive) by central laboratory analysis - Body mass index (BMI) equal to or above 20 kg/m^2 and below 40 kg/m^2 - Insulin naïve subjects; however short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as well as prior insulin treatment for gestational diabetes - A stable daily dose for at least 90 days prior to the day of screening of any SGLT2i in monotherapy or in combination with metformin ± DPP4i ± pioglitazone. Use of pioglitazone is not allowed in subjects treated with dapagliflozin Exclusion Criteria: - Receipt of any investigational medicinal product within 90 days prior to screening - Use of any OADs (other than SGLT2i in monotherapy or in combination with metformin or DPP4i or pioglitazone as described in the inclusion criteria) within 90 days prior to the day of screening - Use of glucagon-like peptide-1 (GLP-1) receptor agonist (e.g., exenatide or liraglutide) within 90 days prior to the day of screening - Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent severe metabolic dysregulation (e.g., diabetes ketoacidosis) in the previous 90 days prior to the day of the screening - Subjects presently classified as being in NYHA (New York Heart Association) Class III or IV1 - Renal impairment estimated Glomerular Filtration Rate 60 mL/min/1.73 m2 as per CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) - Impaired liver function, defined as ALT (alanine aminotransferase) equal to or above 2.5 times upper normal limit at screening - Known or suspected hypersensitivity to trial product(s) or related products ; PRIMARY OUTCOME: Change in HbA1c (Glycosylated Haemoglobin); SECONDARY OUTCOME 1: Change in Body Weight

Yes

TRIAL NAME: Phase I - Single Agent or w/PDR001; BRIEF: The purpose of this "first-in-human" study of FAZ053 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of FAZ053 administered Intravenously (i.v.)as a single agent or in combination with PDR001 in adult patients with advanced solid tumors. By blocking the interaction between Programmed Death Ligand-1 (PD-L1) and its receptors, Programmed Death-1 (PD-1) and B7.1, FAZ053 inhibits the PD-L1 immune checkpoint, resulting in activation of an antitumor immune response by activating effector T-cells and inhibiting regulatory T-cells. This study has been designed as a Phase I, open-label, multi-center study with a dose escalation part of FAZ053 as single agent and in combination with PDR001, followed by a dose expansion part of FAZ053 as single agent. FAZ053 will initially be dosed every three weeks. A less frequent dosing regimen such as every 6 weeks may be evaluated in parallel. A patient may continue treatment with FAZ053 single agent or in combination with PDR001 until the patient experiences unacceptable toxicity, confirmed disease progression per immune related Response Criteria and/or treatment is discontinued at the discretion of the investigator or the patient. ; DRUG USED: LAE005; DRUG CLASS: Biologic; INDICATION: Solid Tumors; TARGET: Immune System, Programmed death-1 receptor (PD-1) / Programmed death ligands (PD-L1 and PD-L2); THERAPY: Monotherapy and Combo Therapy; LEAD SPONSOR: Novartis Pharmaceuticals; CRITERIA: Inclusion Criteria: - Written informed consent prior to any procedure. - Dose escalation cohorts of FAZ053 single agent and FAZ053 in combination with PDR001: Patients with advanced/metastatic solid tumors with measurable or non-measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 who may or may not have received prior treatment with an immune checkpoint inhibitor, who have progressed despite standard therapy, or for whom no standard therapy is available. - Dose expansion groups of FAZ053 single agent: Patients with advanced/metastatic solid tumors with at least one measurable lesion as determined by RECIST version 1.1 who may or may not have received prior treatment with an immune checkpoint inhibitor (for FAZ053 single agent no treatment with an anti-PD-L1 inhibitor is permitted), who have progressed despite standard therapy, or for whom no standard therapy is available and fit into one of the following groups: - FAZ053 single agent: TNBC/ Chordoma/ ASPS - Performance Status (PS) ≤ 2: - Patient must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening/ baseline and during therapy on this study. Exclusion Criteria: - Presence of symptomatic central nervous system (CNS) metastases or CNS metastases that require local CNS-directed therapy (e.g. radiotherapy or surgery) or increasing doses of corticosteroids within the prior 2 weeks. Patients with treated brain metastases should be neurologically stable (for 4 weeks post-treatment and prior to study enrollment) and off of steroids for at least 2 weeks before administration of any study treatment. - History of severe hypersensitivity to study treatment excipients and additives or other monoclonal antibodies (mAbs) and/or their excipients. - Active, known or suspected autoimmune disease. Patients with vitiligo, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur in the absence of an external trigger should not be excluded. Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded. - Treatment with cytotoxic or targeted antineoplastics within 3 weeks of initiation of study treatment. For cytotoxic agents that have major delayed toxicity a washout period of one cycle is indicated (examples are nitrosoureas and mitomycin C which typically require a 6 week washout). Prior antibodies or immunotherapies require a 6 week washout. - Patients receiving systemic chronic steroid therapy or any immunosuppressive therapy (≥ 10mg/day prednisone or equivalent). Topical, inhaled, nasal and ophthalmic steroids are allowed. - Active infection requiring systemic antibiotic therapy. Other protocol-defined inclusion/exclusion criteria may apply. ; PRIMARY OUTCOME: Number of participants with Adverse Events (AEs) as a measure of safety and tolerability; SECONDARY OUTCOME 1: Serum concentration-time profiles of FAZ053 as single agent and FAZ053 in combination with PDR001.

No

TRIAL NAME: Phase I/II - Moderate-to-Severe; BRIEF: A two-component therapeutic consisting of FCX-013 and veledimex for the treatment of localized scleroderma (or morphea). The first component, FCX-013, is autologous human fibroblasts genetically-modified using lentivirus and encoded for matrix metalloproteinase 1 (MMP-1), a protein responsible for breaking down collagen. FCX-013 is designed to be injected under the skin at the location of the fibrotic lesions where the genetically-modified fibroblast cells will produce MMP-1 to break down excess collagen accumulation. With the FCX-013 therapy, the patient will take an oral compound (Veledimex) to induce MMP-1 protein expression from the injected cells. Once the fibrosis is resolved, the patient will stop taking the oral compound which will stop further MMP-1 production from the injected cells. FCX-013 plus veledimex is being developed in anticipation of improving skin function in patients by resolving fibrotic lesions and normalizing dermal collagen production ; DRUG USED: FCX-013; DRUG CLASS: Biologic; INDICATION: Scleroderma; TARGET: Fibroblasts, MMP (metalloproteinase), Stem Cells/Other Cell Therapies; THERAPY: Combination; LEAD SPONSOR: Castle Creek Biosciences, LLC.; CRITERIA: Inclusion Criteria: - Subject is an adult, ≥ 18 years of age with moderate to severe localized scleroderma/morphea with sclerotic lesions which have been unresponsive to standard of care therapy. - Subject has stable control of localized disease (clinically inactive) over the 3 months prior to Screening and through Baseline - Subject has not participated in previous clinical research study in the 3 months prior to Screening and through Baseline - Subject has provided informed written consent - Female subjects of childbearing potential and male subjects engaging in sexual activity that could lead to pregnancy agree to use adequate birth control regimen - Subject is able to understand the study, cooperate with the study procedures and willing to return to the clinic for the required follow-up visits Exclusion Criteria: - Subject has a clinically significant skin disorder other than localized scleroderma/morphea in the anatomical area of interest - Subject has localized scleroderma/morphea only located on the face or over a joint, or lesions that can be successfully managed with topical medications or phototherapy - Subject has symptoms consistent with systemic scleroderma that have not been stable, or that require treatment that has not been stable for 3 months prior to Screening and through Baseline - Subject has been treated with UVA1 phototherapy within 2 months prior to Baseline - Subject requires treatment with a non-stable regimen of systemic immunosuppressive therapy, for any medical condition, or plans to initiate such treatment during the study period - Subject requires treatment with a non-stable regimen of physical therapy, for localized scleroderma/morphea, or plans to initiate such treatment during the study period. - Subject has any medical instability limiting ability to travel to the investigative center. - Subject has clinical signs of infection at (or in close proximity to) the target lesion. - Subject has a history of, or current, malignancy at/near site of injection (except basal cell carcinoma or squamous cell carcinoma that have been treated) - Subject has a history of, or current, clinically significant liver abnormalities. - Subject has a history of, or current, clinically significant cardiac abnormalities, or a significant abnormality on ECG - Subject has clinically significant laboratory abnormalities - Subject has active infection with human immunodeficiency virus (HIV), or hepatitis B/C - Subject has an active drug or alcohol addiction - Subject has any known allergy to any of the constituents of the product - Subject has received an interventional chemical or biological investigational study product for the specific treatment of localized scleroderma in the 3 months prior to Screening and through Baseline - Subject is pregnant or nursing or plans to become pregnant or nurse during the study period ; PRIMARY OUTCOME: Evaluate the Safety of FCX-013 Plus Veledimex; SECONDARY OUTCOME 1: Evaluate the Antifibrotic Effects of FCX-013 Plus Veledimex

No

TRIAL NAME: Phase II - X2202; BRIEF: The purpose of this study was to determine if BVS857 is safe, tolerable and increases thigh muscle thickness in patients with spinal bulbar and muscular atrophy (SBMA). ; DRUG USED: BVS857; DRUG CLASS: New Molecular Entity (NME); INDICATION: Spinal Bulbar Muscular Atrophy (SBMA, Kennedy's Disease, X-linked spinal muscular atrophy type 1); TARGET: IGF-1R (Insulin-like Growth Factor-1 Receptor) ; THERAPY: Monotherapy; LEAD SPONSOR: Novartis Pharmaceuticals; CRITERIA: Key Inclusion Criteria: - Genetic diagnosis of SBMA with symptomatic muscle weakness - Able to complete 2 minute timed walk - Serum IGF-1 level less than or equal to 170 ng/mL Key Exclusion Criteria: - Medically treated diabetes mellitus or known history of hypoglycemia - History of Bell's palsy - Treatment with systemic steroids > 10 mg/day (or equivalent dose); androgens or androgen reducing agents; systemic beta agonists; or other muscle anabolic drugs within the previous 3 months - History of cancer, other than non-melanomatous skin cancer - Retinopathy - Papilledema Other protocol defined inclusion/exclusion criteria may apply ; PRIMARY OUTCOME: Number of Patients With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths as a Measure of Safety and Tolerability; SECONDARY OUTCOME 1: Mean Change From Baseline in Score on the Adult Myopathy Assessment Tool (AMAT) in Part B, Cohort 5

No

TRIAL NAME: Phase II - Pulmonary Sarcoidosis; BRIEF: The purpose of this study is to assess if ACZ885 will improve lung function in association with reduction of tissue inflammation in patients with chronic sarcoidosis. ; DRUG USED: Ilaris; DRUG CLASS: Biologic; INDICATION: Sarcoidosis; TARGET: IL-1 (Interleukin-1); THERAPY: Monotherapy; LEAD SPONSOR: Novartis Pharmaceuticals; CRITERIA: Key Inclusion Criteria: - Male and female subjects ages 18 to 80 years of age (both inclusive) - Pulmonary sarcoidosis disease duration of ≥1 year - Clinically active disease demonstrated either by a biopsy (any organ) or by bronchoalevolar lavage (lymphocytosis >15%, CD4+/CD8+ ration>3.5, CD103+/CD4+/CD4+ ratio <0.2). Patients must also have all of the following criteria: 1. MMRC dyspnea scale ≥1 2. Threshold FVC 50 - 90% of predicted 3. Evidence of parenchymal lung involvement by HRCT at screening or by historical radiological evidence (e.g. CT, MRI or x-ray) Key Exclusion Criteria: - Treated pulmonary hypertension - Previous exposure to concomitant treatment according to the following criteria: 1. Prednisone >15 mg/day or changes in prednisone dose in the 8 weeks prior to screening 2. More than one immune-modulator (i.e., methotrexate, azathioprine, leflunomide, hydroxychloroquine) or changes in their dosing levels within 12 weeks of randomization. 3. Mycophenolate use within 12 weeks of randomization - Prior treatment with any biologic drug targeting the immune system within 180 days of randomization or history of any previous use of rituximab - History of bleeding disorder - Forced vital capacity (FVC) <50% of predicted - Extra-pulmonary sarcoidosis as primary treatment indication (e.g., involving brain, heart, eye and renal disease with significant hypercalcemia) - Any conditions or significant medical problems which in the opinion of the investigator immune-compromise the patient and/or places the patient at unacceptable risk for immunomodulatory therapy, such as: 1. Absolute neutrophil count (ANC) <LLN (1,500/μl) 2. Thrombocytopenia CTCAE v4.03 Grade 1: Platelets <LLN (75.0 x 10exp9/L) 3. Any active or recurrent bacterial, fungal (with exception of onychomycosis) or viral infection 4. Presence of human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C infections based on screening lab results 5. Presence of active or latent tuberculosis (Tb). If historical Tb result is available, Tb status needs to be confirmed pre-randomization as determined by screening laboratory measurements. 6. Clinical evidence or history of multiple sclerosis or other demyelinating diseases, or Felty's syndrome - Live vaccinations within 3 months prior to the start of the trial - Current severe progressive or uncontrolled disease which in the judgment of the clinical investigator renders the patient unsuitable for the trial - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using methods of contraception defined in the protocol for the study. ; PRIMARY OUTCOME: Change Between Baseline and Week 24 in Pulmonary Function as Measured by Spirometry; SECONDARY OUTCOME 1: Change Between Baseline and Week 12 in Pulmonary Tissue Inflammation (Lung Parenchyma) as Measured by SUVmax[F-18]FDG-PET/CT

Yes

TRIAL NAME: Phase III - SevereBD vs. Placebo; BRIEF: NMDA antagonist drugs have increasingly been demonstrated to reduce symptoms of depression and suicidal ideation. NeuroRx has developed a sequential therapy consisting of IV NRX-100 (ketamine HCL) for rapid stabilization of symptoms of depression and suicidal ideation followed by oral NRX-101 (fixed dose combination of D-cycloserine and lurasidone) for maintenance of stabilization from symptoms of depression and suicidal ideation. This study will test the hypothesis that that NRX-100 is superior to placebo in achieving rapid reduction in symptoms of depression and suicidal ideation in patients with Severe Bipolar Depression and Acute Suicidal Ideation or Behavior within 24 hours of administration. ; DRUG USED: Cyclurad; DRUG CLASS: Non-NME; INDICATION: Bipolar Disorder; TARGET: NMDA Glutamate Receptor, Serotonin 5-HT2A receptor; THERAPY: Monotherapy; LEAD SPONSOR: NeuroRx, Inc.; CRITERIA: Inclusion Criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: 1. 18 to 65 years of age, inclusive, at screening. 2. Able to understand and provide written and dated informed consent prior to screening. Deemed likely to comply with study protocol and communicate AEs and other clinically important information, and agree to be hospitalized to complete screening and initiate experimental treatment. 3. Resides in a stable living situation, in the opinion of the investigator 4. Has an identified reliable informant, in the opinion of the investigator 5. Diagnosed with bipolar disorder (BD) according to the criteria defined in the DSM-5. The diagnosis of BD will be made by a psychiatrist and supported by the MINI 7.0.2. 6. Suicidal ideation or behavior as evidenced by an answer of "Yes" to item 4 or item 5 on the C-SSRS. 7. A score of greater than or equal to 20 on the 10 items of the BISS that correspond with MADRS (equivalent to MADRS (BDM) total score of 30). 8. In good general health, as ascertained by medical history, physical examination (including measurement of seated vital signs), clinical laboratory evaluations, and electrocardiogram 9. If female, a status of non-childbearing potential or use of an acceptable form of birth control per the following specific criteria: 1. Non-childbearing potential (e.g., physiologically incapable of becoming pregnant, i.e., permanently sterilized [status post hysterectomy, bilateral tubal ligation], or post-menopausal with last menses at least one year prior to screening); or 2. Childbearing potential, and meets the following criteria: i. Using any form of hormonal birth control, on hormone replacement therapy started prior to 12 months of amenorrhea, using an intrauterine device (IUD), having a monogamous relationship with a partner who has had a vasectomy, or sexually abstinent. ii. Negative urinary pregnancy test at screening, confirmed by a second negative urinary pregnancy test at randomization prior to receiving study treatment. iii. Willing and able to continuously use one of the following methods of birth control during the course of the study, defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly: implants, injectable or patch hormonal contraception, oral contraceptives, IUD, double-barrier contraception, sexual abstinence. The form of birth control will be documented at screening and pre-ketamine baseline. 10. Body mass index between 18-35kg/m2. 11. Concurrent psychotherapy will be allowed if the type and frequency of the therapy (e.g., weekly or monthly) has been stable for at least three months prior to screening and is expected to remain stable for the duration of the study. 12. Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin, benzodiazepines, or trazodone) will be allowed if the therapy has been stable for at least four weeks prior to screening and if it is expected to remain stable during the course of the subject's participation in the study. Subjects can also continue treatment with benzodiazepines used for anxiety if therapy has been stable for at least four weeks prior to screening and if it is expected to remain stable during the course of the subject's participation in the study. Exclusion Criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study. 2. Female who is pregnant or breastfeeding. 3. Female with a positive pregnancy test at screening or before oral dosing of investigational product. 4. Current DSM-5 diagnosis of moderate or severe substance use disorder (except marijuana or tobacco use disorder) within the 12 months prior to screening. Substance abuse cannot be the precipitant of entry to treatment. 5. Subjects with a lifetime history of PCP/ketamine drug use, or failed use of ketamine for depression. 6. History of schizophrenia or schizoaffective disorder, or any history of psychotic symptoms when not in an acute bipolar mood episode. 7. History of anorexia nervosa, bulimia nervosa, or eating disorder NOS (OSFED) within five years of screening. 8. Has dementia, delirium, amnestic, or any other cognitive disorder. 9. Any major psychiatric disorder, including a personality disorder, which is clinically predominant to BD at screening, or has been the primary focus of treatment predominant to BD at any time within six months prior to screening. 10. Current major psychiatric disorder, diagnosed at screening with the MINI 7.0.2, that is the primary focus of treatment, with BD as the secondary focus of treatment, within the past six months. 11. A clinically significant abnormality on the screening physical examination that might affect safety or study participation, or that might confound interpretation of study results according to the study clinician. 12. Current episode of: 1. Untreated hypertension, (Stage 1 or greater) as defined by a systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg at screening on two of three measurements at least 15 minutes apart. If untreated due to missing medication dose/s this is not exclusionary. 2. Hypertension, Stage 2, as defined by a systolic blood pressure ≥155 mmHg or diastolic blood pressure ≥99 mmHg within 1.5 hours prior to ketamine infusion on two of three measurements at least 15 minutes apart at the pre-ketamine assessment (on Day 0 at Visit 1). 3. Recent myocardial infarction (within one year). 4. Syncopal event within the past year. 5. Congestive heart failure (CHF) New York Heart Association Criteria >Stage 2. 6. Angina pectoris. 7. Heart rate <50 or >105 beats per minute at screening, pre-ketamine infusion (Day 0) or at randomization (Day 1). 8. QTcF ≥450 msec at screening for men, ≥ 470 msec for women, pre-ketamine infusion (Day 0), or at randomization (Day 1), on two of three measurements at least 15 minutes apart. 13. History of hypertension, or on antihypertensives for the purpose of lowering blood pressure, with either an increase in antihypertensive dose or increase in the number of antihypertensive drugs used to treat hypertension over the last two months. 14. Chronic lung disease, excluding asthma. 15. Lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system (CNS) disorder (e.g., Alzheimer's or Parkinson's Disease), epilepsy, mental retardation, or any other disease/procedure/accident/intervention that, according to the screening clinician, is deemed associated with significant injury to or malfunction of the CNS; or history of significant head trauma within the past two years. 16. Presents with any of the following lab abnormalities: a. Subjects with diabetes mellitus fulfilling any of the following criteria: i. Unstable diabetes mellitus defined as glycosylated hemoglobin (HbA1c) >8.0 % at screening. ii. Admitted to hospital for treatment of diabetes mellitus or diabetes mellitus-related illness in the past 12 weeks. iii. Not under physician care for diabetes mellitus. iv. Has not been on the same dose of oral hypoglycemic drug(s) and/or diet for the four weeks prior to screening. For thiazolidinediones (glitazones) this period should not be less than eight weeks. b. Any other clinically significant abnormal laboratory result (as determined by the investigator and medical monitor) at the time of the screening. 17. Any current or past history of any physical condition which, in the investigator's opinion, might put the subject at risk or interfere with study results interpretation. 18. Subjects on exclusionary concomitant psychotropic medications (see Appendix 1) as defined in the study manual. 19. At randomization, subjects prescribed more than one agent in each category; 1. Approved antidepressants (e.g., SSRIs, SNRIs, TeCAs, fluoxetine), but not 5-HT-2a antagonists (lurasidone, aripiprazole, olanzapine, quetiapine) 2. Mood stabilizers (e.g., lithium, carbamazepine, valproic acid) 20. Subjects with exclusionary laboratory values (see Table 2). 21. Known allergies to lurasidone or Latuda, cycloserine or Seromycin, or the excipients mannitol, croscarmellose sodium, magnesium stearate, silicon dioxide, and/or HPMC (hydroxypropylmethylcellulose). 22. Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation. 23. Study site personnel and/or persons employed by NeuroRx, Inc. or Target Health or by the investigator or study site (i.e., permanent, temporary contract worker, or designee responsible for the conduct of the study), or an immediate family member (i.e., spouse or parent, child, or sibling [biological or legally adopted]) of such persons. ; PRIMARY OUTCOME: Suicidal Ideation; SECONDARY OUTCOME 1: Depression

No

TRIAL NAME: Phase II - BIANCA-SC; BRIEF: The purpose of this study is to evaluate efficacy, safety and tolerability of blisibimod when taken with methotrexate in the induction of remission in ANCA-Associated Small Vessel Vasculitis. ; DRUG USED: Blisibimod; DRUG CLASS: Biologic; INDICATION: Antineutrophil Cytoplasmic Antibodies (ANCA) Associated Vasculitis; TARGET: B-cell activating factor (BAFF); THERAPY: Monotherapy; LEAD SPONSOR: Anthera Pharmaceuticals; CRITERIA: Inclusion Criteria: 1. 18 years of age or older (male or female). 2. Granulomatosis with polyangiitis (GPA, or Wegener's granulomatosis) or microscopic polyangiitis (MPA) according to the definitions of the American College of Rheumatology and Chapel Hill Consensus Conference. 3. Active GPA or MPA disease at screening. 4. Positive for either PR3-ANCA or MPO-ANCA at screening. 5. Subject willing to initiate corticosteroids and methotrexate (MTX) if not already on corticosteroids and/or MTX at baseline. 6. Clinical intention to prescribe MTX therapy for treatment of GPA or MPA. Exclusion Criteria: 1. Diagnosed with Churg Strauss syndrome. 2. Severe GPA or MPA disease that would conventionally be treated with cyclophosphamide. 3. Nursing or pregnant. 4. Active systemic infection or deep-space infection. 5. Active hepatitis B, active hepatitis C or a documented history of HIV, hepatitis B, or hepatitis C. 6. Liver disease. 7. History of documented anti-glomerular basement membrane (GBM) disease. 8. Malignancy within the past 5 years. 9. History of active tuberculosis (TB) or history of TB infection. 10. Anemia, neutropenia, or thrombocytopenia. 11. Serum creatinine level greater than 2.5 mg/dL. 12. Prior administration of a B-cell modulating therapy other than rituximab. 13. Subject has not yet completed at least 3 months or 5 half-lives (whichever is longer) since ending other investigational study. 14. History of congenital immunodeficiency. ; PRIMARY OUTCOME: Induction of clinical remission; SECONDARY OUTCOME 1: Time to complete remission

No

TRIAL NAME: Phase II - CAPS - 201 Study; BRIEF: This is a Phase 2 study to investigate the safety and efficacy of ATI-450 for the Maintenance of Remission in Patients with Cryopyrin-Associated Periodic Syndrome (CAPS) Previously Managed with Anti-IL-1 Therapy. ; DRUG USED: ATI-450; DRUG CLASS: New Molecular Entity (NME); INDICATION: Cryopyrin (CIAS1)-Associated Periodic Syndromes (CAPS); TARGET: Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK2), p38 MAP kinase (MAPK); THERAPY: Monotherapy; LEAD SPONSOR: Aclaris Therapeutics, Inc.; CRITERIA: Inclusion Criteria: - Diagnosis of Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease. Prior agreement between the Investigator and Aclaris for study eligibility is required for patients who do not have a molecular diagnosis of NALP3 mutations available (either testing not performed, or testing performed, but negative) upon study entry. For those patients who have not been molecularly tested for NALP3 mutations, molecular testing should be performed during the study. - Patients with a PGA score of "minimal" or less and hsCRP and SAA values within the normal range (≤10mg/L), and who are considered to have achieved that response as a result of successful anti-IL-1 therapy. - Continuous Treatment with anti-IL1 therapy for at least 6 months. - Able to understand and comply with study procedures and able to provide informed consent. - Male or non-pregnant, non-nursing female patients at least 18 years of age, inclusive. - Female patients who are of childbearing potential must use 2 methods of highly effective contraception* - one of which must be a physical barrier- for the duration of the study and for 30 days after the last dose. - Male patients of childbearing potential with a female partner of childbearing potential must agree to use a condom plus another highly effective form of birth control for the duration of the study and for 90 days after the last dose. - Female patients must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to dosing on Day 1. - Willing and capable of taking appropriate Covid-19 risk mitigation precautions (e.g. wearing a mask in public, adhering to social distancing, etc.) as required by local, state, or federal guidelines during participation in the study. Exclusion Criteria: - Participation in any clinical study with an investigative agent within 12 weeks prior to entry or within 5 half-lives of the investigational agent. - Being treated with another immuno-suppressive agent (i.e., in addition to an anti-IL-1 product) for CAPS syndrome (anti- IL-1 therapy will have been used for at least 6 months and will be stopped at study entry). - Use of any of the following treatments within the indicated washout period prior to the baseline visit: - Systemic immunosuppressant or immunomodulatory therapy (e.g., etanercept, alefacept, infliximab, methotrexate) within 16 weeks prior to Visit 2 (excluding anti- IL-1 therapy for CAPS). - Janus Kinase (JAK) inhibitors (systemic or topical) within 4 weeks prior to Visit 2. - Systemic corticosteroids within 4 weeks prior to Visit 2 (Intranasal, inhaled, and topical ocular corticosteroids are allowed). - History of being immunocompromised, including a positive HIV at screening (ELISA and Western blot) test result. [Previous treatment with anti-IL1 therapy is not an exclusion] - A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody test result. - Live vaccinations within 3 months prior to the start of the trial, or during the trial. - History of recurrent and/or evidence of active bacterial, fungal, or viral infections. - History or evidence of active or latent tuberculosis (TB). - Tests performed at a central laboratory at screening that meet any of the criteria below (out of range labs may be rechecked one time, after consultation with sponsor or designee, before patient is considered a screen failure): - White blood cell (WBC) count <3.0×103 cells/mm3 - Absolute neutrophil count (ANC) <1.5×103 cells/mm3 - Lymphocyte count <0.5×103 cells/mm3 - Platelet count <100×103 cells/mm3 - Hemoglobin <10 g/dL - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2×upper limit of normal (ULN) - Total bilirubin level >2×ULN, unless patient has been diagnosed with Gilberts' disease and this is clearly documented - Estimated glomerular filtration rate Estimated glomerular filtration rate (eGFR), <40 mL/min/1.73m2 based on Modification of Diet and Renal Disease formula - Any clinically significant laboratory abnormality that would affect interpretation of study data or safety of the patient's participation in the study, per the judgment of the investigator. - Patient has clinically significant abnormal findings other than CAPS from physical examination that may affect the interpretation of study data or the safety of the patient's participation in the study, per the judgment of the investigator. - Patient has a clinically important history of a medical disorder that would compromise patient safety or data quality, per the judgement of the investigator. - Blood pressure (BP) levels (in supine position after at least 5 minutes rest): <90 mmHg or >140 mmHg for systolic BP or <40 mmHg or >90 mmHg for diastolic blood pressure. - Patients with history of stroke. - Significant cardiac disease that would affect interpretation of study data or the safety of the patient's participation in the study, per the judgment of the investigator, including recent myocardial infarction or unstable angina, or heart failure with New York Heart Association Class III or IV symptoms. - Patients with the following screening or pre-dose ECG findings, specifically: - Evidence of atrial fibrillation, atrial flutter, complete right or left bundle branch block, Wolff-Parkinson-White Syndrome, or other significant rhythm disturbance - Evidence of acute ischemia - Screening or pre-dose baseline mean QTcF >450 msec for males or >470 msec for females (use of the ECG algorithm is acceptable for this purpose) - Personal or family history of congenital long QT syndrome or sudden death - Any other finding that is considered clinically significant - A confirmed diagnosis of Covid-19 at baseline or at any time during the study. ; PRIMARY OUTCOME: Number of Participants With Treatment-emergent Adverse Events (TEAEs); SECONDARY OUTCOME 1:

No

TRIAL NAME: Phase I - 150169 (NIAID); BRIEF: Background: - Malaria is a severe infection caused by a parasite. People can get malaria if a mosquito that carries the parasite bites them. Although malaria does not occur in the United States, many people in Africa, Asia, and South America do get malaria. In some cases, malaria can cause death. In 2013 alone, 584,000 people died due to malaria. Researchers want to find ways to prevent and treat malaria. Objective: - To find out if combining live, infectious malaria parasites (known as Sanaria PfSPZ Challenge) and two FDA approved drugs that kill malaria parasites (pyrimethamine [PYR] and chloroquine [CQ]) is safe and can provide people protection against malaria. The Sanaria PfSPZ Challenge has been used in other studies without significant side effects. Eligibility: - Healthy people ages 18-50 who weigh less than 170 pounds and are not pregnant or breastfeeding - No history of hepatitis B, hepatitis C, or HIV infection - Not currently enrolled in a clinical trial that involves a research drug or vaccine - Have not traveled to an area with high malaria transmission within the last 5 years - Never diagnosed with malaria in the past Design: - Participants will be in 1 of 4 groups. - Participants will receive a combination of injections and drugs. What combination they will receive will depend on what group they are in. This combination of injections and drugs may include: - Injections of Sanaria PfSPZ Challenge (live, infectious malaria parasites) into a vein - FDA approved antimalarial drug called chloroquine (CQ) - FDA approved antimalarial drug called pyrimethamine (PYR) - FDA approved antimalarial drug called Malarone - The study will last approximately 3-7 months (depending on which group participants are in). - There will be up to 68 study visits for three groups. One group will have up to 27 study visits. During the study visits, participants may have: - Medical history review - Physical exams - Electrocardiogram (ECG): soft electrodes will be placed on the skin. A machine will record the heart s electrical signals to evaluate heart function. - Blood and urine tests - Medication given in the clinic under direct observation - Injection of Sanaria PfSPZ Challenge into a vein - Participants will receive a diary, thermometer, and ruler to record their body temperature and any symptoms. ; DRUG USED: PfSPZ Vaccine; DRUG CLASS: Vaccine; INDICATION: Malaria; TARGET: Immune System, Interferon-gamma (IFN-g)/Type II Interferon, Plasmodium, T-Cell Receptor (TCR); THERAPY: Monotherapy; LEAD SPONSOR: National Institute of Allergy and Infectious Diseases (NIAID); CRITERIA: - INCLUSION CRITERIA: All of the following criteria must be fulfilled for a subject to participate in this trial: 1. Age greater than or equal to 18 and less than or equal to 50 years. 2. In good general health and without clinically significant medical history 3. Malaria comprehension exam completed, passed (a score of greater than or equal to 80% or per investigator s discretion) and reviewed prior to enrollment 4. Reliable access to the clinical trial center and availability to participate for duration of study 5. Females of childbearing potential must be willing to use reliable contraception (as defined below) from 21 days prior to study day -2 to 28 days following last Sanaria . - Subject to the judgment and discretion of the PI, female participants who meet ANY ONE of the criteria listed immediately below, may not be required to take any additional measures to avoid pregnancy. Such participants will be counseled on risks at the time of consent and at appropriate points (e.g. when pregnancy testing occurs) during the study: - Females who have had their uterus, and/or BOTH ovaries removed - Females who have had BOTH fallopian tubes surgically tied or removed - Females who are above the age of 45 and have spontaneously had no menses at any point during the past 12 or more consecutive months (i.e. have reached menopause) - Females who, in the conservative and reasonable judgment of the PI (e.g. due to sexual orientation or serious life choice (such as being celibate clergy or transgender), during the entire trial will NOT participate in any potentially reproductive sexual contact - Females who, in the conservative and reasonable judgment of the PI, are in a monogamous stable relationship with a male who has undergone vasectomy at least 4 months prior or another procedure/medical condition that deems the male sterile - Subject to the judgment and discretion of the PI, female participants who DO NOT meet ANY of the criteria listed above, will be appropriately counseled on reproductive risks and pregnancy avoidance, and will be required to adhere to the following measures and agree to 2 methods of pregnancy prevention as noted below: CATEGORY 1: - a highly effective hormonal method to prevent pregnancy [e.g. CONSISTENT, CONTINUOUS use of contraceptive pill, patch, ring, implant or injection], and/or - IUD or equivalent IN ADDITION TO CATEGORY 2: -a barrier method to be used at the time of potentially reproductive sexual activity (e.g. [male/female condom, 'cap,' or diaphragm] plus spermicide). EXCLUSION CRITERIA: A subject will be excluded from participating in this trial if any one of the following criteria is fulfilled: 1. Currently is breast-feeding (if female). 2. Pregnancy as determined by a positive urine or serum human choriogonadotropin (beta-hCG) test at any point during the study (if female). 3. Recent travel to a malaria endemic area within 5 years of enrollment 4. Planned travel to a malaria endemic area during the study period 5. History of confirmed malaria diagnosis on peripheral blood smear or by clinical history in the past 10 years. 6. Hemoglobin, WBC, platelets, ALT, and creatinine outside of local lab normal range (subjects may be included at the investigator s discretion for not clinically significant values outside of normal range) 7. Abnormal urinalysis as defined by positive urine glucose, protein, and hemoglobin. Subject can be included if investigator determine the abnormality is not clinically significant . 8. Anticipated use during the study period, or use within the following periods prior to enrollment: 1. Investigational malaria vaccine within the last five years 2. Malaria chemoprophylaxis within 6 months 3. Chronic systemic immunosuppressive medications (>14 days) within 6 months (e.g.cytotoxic medications, oral/parental corticosteroids >0.5 mg/kg/day prednisone or equivalent). Corticosteroid nasal spray for allergic rhinitis and topical corticosteroids for mild, uncomplicated dermatitis are allowed. 4. Blood products or immunoglobulins within 6 months 5. Systemic antibiotics with antimalarial effects within 30 days (such as clindamycin, doxycycline) 6. Investigational or non-registered product or vaccine within 30 days 7. Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior to Sanaria PfSPZ Challenge 8. Medications known to interact with pyrimethamine, chloroquine, atovaquone, proguanil (during the study period only) 9. History of: 1. Sickle cell disease, sickle cell trait, or other hemoglobinopathies 2. Splenectomy or functional asplenia 3. Systemic anaphylaxis 4. Any allergic reactions to study drugs 5. Documented history of chronic or active neurologic disease (including seizures, uncontrolled migraine headaches) 6. Psoriasis or porphyria 7. Ocular diseases including retinopathy or visual field defects 10. Clinically significant medical condition, physical examination findings, other clinically significant abnormal laboratory results, or past medical history that may have clinically significant implications for current health status and participation in the study in the opinion of the Investigator. A clinically significant condition or process includes but is not limited to: 1. A process that would affect the immune response, or requires medication that affects the immune response 2. Any contraindication to repeated phlebotomy 3. A condition or process in which signs or symptoms could be confused with reactions to malaria challenge and/or infection, including dermatologic abnormalities at the site of sporozoite inoculation 4. A chronic or subclinical condition which could be exacerbated by administration of any of the PfSPZ-CVac components or malaria infection 11. Weight > 77.2 Kg at the time of screening (this will result in a minimum dose of pyrimethamine of approximately 0.7mg/Kg for a 50mg daily dose). (Note not required for Arm 4 CHMI controls) 12. History of, or known active cardiac disease including: (1) prior myocardial infarction (heart attack); (2) angina pectoris; (3) congestive heart failure; (4) valvular heart disease; (5) cardiomyopathy; (6) pericarditis; (7) stroke or transient ischemic attack; (8) exertional chest pain or shortness of breath; or ( 9) other heart conditions under the care of a doctor 13. Clinically significant ECG findings, as determined by the expert study cardiologist 14. Moderate or high risk for coronary heart disease (CHD) based on NHANES I cardiovascular risk assessment 15. Acute illness at the time of enrollment 16. Infection with HIV, Hepatitis B, Hepatitis C 17. Psychiatric condition that precludes compliance with the protocol including but not limited to: 1. Psychosis within the past 3 years 2. Ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years 18. Suspected or known current alcohol or drug abuse as defined by the American Psychiatric Association in the DSM V at the discretion of the PI 19. Clinical trial staff and/or Sanaria employees with direct involvement in the conduct of the trial are excluded from participation. 20. Participating in other clinical trials involving investigational interventions or off label medication use during the study period (excluding participation in the optional long term follow up visits). Participation in other trials such as observational or imaging studies will be discussed with the investigators. 21. Any other finding that, in the judgment of the Investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a subject s ability to give informed consent, or increase the risk of having an adverse outcome from participating in the study ; PRIMARY OUTCOME: Incidence and severity of local and systemic adverse events (AEs) and serious adverse events (SAEs) occurring after each Sanaria PfSPZ Challenge (Safety); SECONDARY OUTCOME 1: P. falciparum blood stage infection defined as detection of at least 2 P.falciparum parasites by microscopic examination of 0.5 L of blood or two consecutive positive diagnostic qRTPCR following homologous CHMI. (Protective Efficacy)

Yes

TRIAL NAME: Phase III - Pain Treatment (Japan); BRIEF: The purpose of this study is to evaluate the efficacy and safety of Relugolix (TAK-385) in patients having pain symptoms associated with uterine fibroids. ; DRUG USED: Orgovyx; DRUG CLASS: New Molecular Entity (NME); INDICATION: Uterine Fibroids; TARGET: Gonadotropin-Releasing Hormone (GnRH) Receptor; THERAPY: Monotherapy; LEAD SPONSOR: Takeda; CRITERIA: Inclusion Criteria: Inclusion Criteria for Entering the Screening Period (at VISIT 1) 1. In the opinion of the investigator or subinvestigator, the participant is capable of understanding and complying with protocol requirements. 2. The participant signs and dates a written, informed consent form prior to the initiation of any study procedures. 3. Prior to VISIT 1, the participant has a diagnosis of uterine fibroids confirmed by transvaginal ultrasound, abdominal ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), or laparoscopy, and has never received any surgical treatment for the myoma (measurable noncalcified myoma with a longest diameter of ≥3 cm). 4. The participant is a premenopausal Japanese woman. 5. The participant is aged 20 years or older on the day of signing and dating the informed consent form. 6. The participant has 1 or more measurable noncalcified myomas with a longest diameter of ≥3 cm confirmed by transvaginal ultrasound. 7. The participant has experienced 1 or more regular menstrual cycles (25 to 38 days) immediately prior to VISIT 1 and that should include menstrual bleeding for at least 3 consecutive days. 8. The participant who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the study. Inclusion Criteria for Entering the Run-in Period (at VISIT 2) 9. The participant has experienced regular menstrual cycles (25 to 38 days) immediately prior to VISIT 2 that should include menstrual bleeding for at least 3 consecutive days (at least 2 regular menstruation cycles to be confirmed by Inclusion criteria #7 and #9). Inclusion Criteria for Entering the Treatment Period (at VISIT 3) 10. The participant has 1 or more measurable noncalcified myomas, with a longest diameter of ≥3 cm confirmed by transvaginal ultrasound (the same myoma should be measured in Inclusion criterion #6). 11. The participant has a maximum Numerical Rating Scale (NRS) score of ≥4 during 1 menstrual cycle just before VISIT 3. 12. The participant has pain symptoms associated with uterine fibroids for at least 2 days during 1 menstrual cycle just before VISIT 3. 13. The participant has experienced regular menstrual cycles (25 to 38 days) after VISIT 1 that should include menstrual bleeding for at least 3 consecutive days (at least 3 regular menstruation cycles to be confirmed by Inclusion criteria #7, #9 and #13). Exclusion Criteria: 1. The participant has received any investigational compound within 24 weeks prior to the start of the administration of the study drug for the day of first menstruation after VISIT 1. 2. The participant has received relugolix (including placebo) in a previous clinical study. 3. The participant is an immediate family member or study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, or sibling) or may consent under duress. 4. The participant has lower abdominal pain due to irritable bowel syndrome or severe interstitial cystitis. 5. The participant has a current history of thyroid gland disorder with irregular menstruation, or has a potential for irregular menstruation due to thyroid gland disorder, as determined by the investigator or subinvestigator. 6. The participant has a previous or current history of pelvic inflammatory disease within 8 weeks prior to VISIT 1. 7. The participant has a positive Pap smear test result obtained within 1 year prior to VISIT 1 (if there are no previous test results, those who were judged positive in the test conducted before VISIT 2). 8. The participant has a history of panhysterectomy or bilateral oophorectomy. 9. The participant has had markedly abnormal uterine bleeding or anovulatory bleeding, as determined by the investigator or subinvestigator. 10. The participant has a malignant tumor or a history of a malignant tumor within 5 years prior to VISIT 1. 11. The participant has been treated with selective estrogen receptor modulators (SERMs) (excluding drugs for external use and dietary supplements) within 4 weeks prior to VISIT 2. 12. The participant has been treated with any of the following drugs within 8 weeks prior to VISIT 2: oral contraceptive or sex hormone preparations (norethindrone, norethisterone, medroxyprogesterone, estrogen, or other progestins), and within 16 weeks prior to VISIT 2: gonadotropin-releasing hormone (GnRH) analogues, dienogest, danazol, or aromatase inhibitors (for 1- and 3-month sustained-release preparations, within 20 and 28 weeks prior to VISIT 2, respectively). 13. The participant has a previous or current history of severe hypersensitivity or severe allergies to drugs. 14. The participant has nondiagnosable abnormal genital bleeding. 15. Female participant who is pregnant, lactating, or intending to become pregnant or to donate ova prior to the signing of informed consent, during the study period, or within 1 month after the end of the study. 16. The participant has clinically significant cardiovascular disease (eg, myocardial infarction or unstable angina pectoris within 24 weeks prior to VISIT 1) or uncontrollable hypertension (eg, resting systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg at Screening and Run-in Period). 17. The participant is ineligible for this study based on standard 12-lead electrocardiogram (ECG) findings, as determined by the investigator or subinvestigator. 18. The participant has active liver disease or jaundice, or with alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin (total bilirubin) >1.5 times the upper limit of normal (ULN) in the clinical laboratory tests at VISIT 1 and 2. 19. The participant has a previous or current history of diseases considered to be ineligible for this study, including severe hepatic impairment, jaundice, renal impairment, cardiovascular disease, endocrine system disease, metabolic disorder, pulmonary disease, gastrointestinal disease, neurological disease, urological disease, immune disease, mental disorder (especially depression-like symptoms) and suicide attempt resulting from a mental disorder. 20. The participant has a previous or current history of drug abuse (defined as any illicit drug use) or alcohol abuse. 21. The participant is ineligible for this study for other reasons, as determined by the investigator or subinvestigator. ; PRIMARY OUTCOME: Percentage of Participants With a Maximum NRS Score of 1 or Less During the 28 Days Before the Final Dose of Study Drug; SECONDARY OUTCOME 1: Percentage of Participants With a Maximum NRS Score of 0 During the 28 Days Before the Final Dose of Study Drug

Yes

TRIAL NAME: Phase II - C2501007; BRIEF: This is a study with 3 kinase inhibitors (PF 06650833, PF 06700841 and PF 06826647) in participants with moderate to severe HS. The study will have a maximum duration of approximately 26 weeks. This includes an up to 6-week Screening Period, a 16 week Dosing Period and a 4 week Follow up Period. ; DRUG USED: PF-06650833; DRUG CLASS: New Molecular Entity (NME); INDICATION: Hidradenitis Suppurativa; TARGET: Interleukin-1 receptor-associated kinase 4 (IRAK4); THERAPY: Monotherapy; LEAD SPONSOR: Pfizer; CRITERIA: Inclusion Criteria: - male or female participants, between 18-75, with a diagnosis of moderate to severe Hidradenitis Suppurativa Exclusion Criteria: - History of human immunodeficiency virus (HIV) or positive HIV serology at screening, - Infected with hepatitis B or hepatitis C viruses. - Have evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) ; PRIMARY OUTCOME: Percentage of Participants Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 16- Minimum Risk (MR) [Full Analysis Set (FAS), Non-responder Imputation (NRI)].; SECONDARY OUTCOME 1: Percentage of Participants Achieving HiSCR Response at Weeks 1, 2, 4, 6, 8, and 12 - MR (FAS, NRI).

Yes

TRIAL NAME: Phase II - 09-07 (Low or Int-1); BRIEF: The study will enroll low risk MDS patients who need red blood cell transfusions and who are refractory to or are not using erythropoiesis-stimulating agents. The purpose of the study is to determine whether oral rigosertib treatment results in hematological improvements according to the 2006 International Working Group criteria in these patients. The study will also record any side effects that may occur during the study. ; DRUG USED: Estybon (Oral); DRUG CLASS: New Molecular Entity (NME); INDICATION: Myelodysplastic Syndrome (MDS); TARGET: PI3K/AKT pathway, Polo-like kinase 1 (Plk1); THERAPY: Monotherapy; LEAD SPONSOR: Onconova Therapeutics, Inc.; CRITERIA: Inclusion Criteria: - Diagnosis of MDS according to World Health Organization (WHO) criteria (Appendix 2) or French-American-British (FAB) classification that must be confirmed by bone marrow (BM) aspirate and/or biopsy within 6 weeks prior to Screening. - Myelodysplastic syndrome (MDS) classified as Low risk or Int-1 risk, according to International Prognostic Scoring System (IPSS) classification; in addition, patients should never have been classified as Int-2 or High-risk since their MDS was diagnosed; - Transfusion dependency defined by transfusion of at least 4 units of Red blood cells (RBC) within 56 days before Screening (pre-transfusion Hgb values values must be ≤ 9 g/dL to be taken into account). - Refractory to 8- to 12-week course of Erythropoiesis-stimulating agent (ESA) administered within the past 2 years before enrollment, or erythropoietin (EPO) level ˃ 500 mU/mL and off ESA for at least 8 weeks before Screening. - Off all other treatments for MDS (azacitidine, decitabine, lenalidomide, chemotherapy, immunotherapy) for at least 2 weeks prior to Screening. - Eastern Cooperative Oncology Group(ECOG) performance status of 0, 1 or 2. - Willing to adhere to the prohibitions and restrictions specified in this protocol. - The patient must signed an informed consent form (ICF) indicating that s/he understands the purpose of, and procedures required for, the study and is willing to participate. Exclusion Criteria: - Ongoing clinically significant anemia due to factors such as iron, vitamin B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal (GI) bleeding. - Serum ferritin < 50 ng/mL. - Hypoplastic MDS (cellularity <10%) - Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast. - Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. - Active infection not adequately responding to appropriate therapy. - Total bilirubin ≥ 2.0 mg/dL not related to hemolysis or Gilbert's disease. - Alanine transaminase (ALT) or aspartate transaminase (AST) ≥ 2.5 x the upper limit of normal (ULN). - Serum creatinine ≥ 2.0 mg/dL. - Ascites requiring active medical management including paracentesis. - Hyponatremia (defined as serum sodium value of < 130 mEq/L). - Female patients who are pregnant or lactating. - Patients of childbearing potential who are unwilling to follow strict contraception requirements. - Female patients with reproductive potential who do not have a negative blood or urine pregnancy test at Screening. - Major surgery without full recovery or major surgery within 3 weeks of Screening. - Uncontrolled hypertension (defined as a systolic pressure ≥ 160 mmHg and/or a diastolic pressure ≥ 110 mmHg). - New onset seizures (within 3 months prior to the first dose of rigosertib) or poorly controlled seizures. - Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy. - Chronic use (˃ 2 weeks) of corticosteroids (˃ 10 mg/24 hr equivalent prednisone) within 4 weeks of Screening. - Investigational therapy within 4 weeks of Screening. - Allergy to a local anaesthetic. - Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements. ; PRIMARY OUTCOME: Hematologic Improvement; SECONDARY OUTCOME 1: Overall Response

No

TRIAL NAME: Phase II - Sputum Eosinophilia; BRIEF: GW766994 is a selective, competitive antagonist of the human CC chemokine receptor-3 (CCR3). It is proposed that the inhibition of the CCR3 receptor may provide a treatment for airway inflammation such as in asthma. This will be a double-blind, placebo controlled, parallel group study being conducted to evaluate the effects of GW766994 in subjects with mild-moderate asthma who have high sputum eosinophilia. The primary objective is to compare the effects of GW766994 to placebo on sputum eosinophils. ; DRUG USED: GW766944; DRUG CLASS: New Molecular Entity (NME); INDICATION: Asthma; TARGET: Chemokine Receptor 3 (CCR3); THERAPY: Monotherapy; LEAD SPONSOR: GlaxoSmithKline; CRITERIA: Inclusion Criteria: - Physician diagnosis of asthma (>12% improvement in FEV1 with a bronchodilator or PC20 methacholine less than 8 mg/ml) documented within the past 2 years. - Males and females aged ≥18-75 years inclusive. - A female subject is eligible to participate if she is of: - Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory]. - Child-bearing potential and agrees to use one of the contraception methods listed in Section 9.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 2 days after the last dose of GW766994. - Non smoker. Current smokers with a with a pack history of less than 10 years may be enrolled into the study. Subjects who only use chewing tobacco products may be enrolled at the discretion of the Investigator and after consultation with the GSK medical monitor. - Sputum eosinophils >4.9%. - AST, ALT, alkaline phosphatase and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). - QTcB or QTcF < 450 msec assessed within 6 months of the screening visit. - To be eligible, female patients must have a negative urine pregnancy test. - Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. - The subject is able to understand and comply with protocol requirements, instructions and protocol- stated restrictions. Exclusion Criteria: - Any clinically relevant abnormality identified on the screening medical assessment, laboratory examination, or ECG. - Current smokers. - Subjects unable to produce a technically acceptable sputum sample. - Sputum TCC >25 million cells/g. - Clinically significant hepatic impairment or current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) - Positive HIV, Hepatitis B surface antigen or Hepatitis C antibody within 3 months of screening. - The subject regularly drinks more than 28 units of alcohol in a week, if male or 21 units per week, if female. One unit of alcohol is defined as a medium (125ml) glass of wine, half a pint (250ml) of beer, or one measure (25ml) of spirits. - Pregnant and lactating women. - Asthma considered unstable within 2 months prioir to screening. - Respiratory Infection: Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within the 4 weeks before screening and led to a change in asthma management, or in the opinion of the Investigator is expected to affect the subjects asthma status or the subjects ability to participate in the study. - Baseline post-bronchodilator FEV1 <50% predicted (spirometry to be done at screening visit). - Regular oral prednisone use. - Subjects who have received therapy with monoclonal antibodies within the proceeding 3 months prior to screening visit. - Co-morbidities that, in the investigator's opinion may interfere with study including systemic inflammatory conditions such as rheumatoid arthritis. - Donation of blood in excess of 500 mL within a 56-day period prior to dosing - Participation in a trial with any drug within 30 days or 5 half-lives (whichever is longer), or participation in a trial with a new chemical entity within 2 months prior to first dose of current study medication, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study procedures or compromise subject safety. - The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened but not limited to amphetamines, barbiturates, cocaine, opiates, and cannabinoids. Subjects who use benzodiazepines or other anxiolytic on a regular basis can be included at the discretion of the investigator and in consultation with the GSK medical monitor. - Cytochrome P450 3A4 inhibitors including but not limited to antiretrovirals (protease inhibitors) (e.g.indinavir, nelfinavir, ritonavir, saquinavir); imidazole and triazole anti-fungals (e.g. ketaconazole, itraconazole); macrolide antibiotics (e.g. clarithromycin, erytrhomycin and; telithromycin); calcium channel blockers (diltiazem and verapamil) and nefazodone, 6 weeks before. - Consumption of seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication. - Unwillingness or inability to follow the procedures outlined in the protocol. ; PRIMARY OUTCOME: Number of eosinophils (absolute cell count) in induced sputum; SECONDARY OUTCOME 1: Number of eosinophils (absolute cell count) in blood

No

TRIAL NAME: Phase I - Safety/Tolerability; BRIEF: This is a single arm, open-label, multicenter phase I study to assess the safety, tolerability and preliminary efficacy of autologous T cells transduced with a specific γδTCR, i.e. TEG002, in a dose escalation and expansion study in relapsed/refractory Multiple Myeloma patients. The study will comprise of a Dose Escalation Segment and an Expansion Segment. The study consists of a screening period, leukapheresis of mononuclear cells, and conditioning chemotherapy, followed by TEG002. All subjects continue to be followed regularly for safety and efficacy assessments until 1 year after TEG002 administration. ; DRUG USED: GDT-002; DRUG CLASS: Biologic; INDICATION: Multiple Myeloma (MM); TARGET: Immune System, Stem Cells/Other Cell Therapies, T-Cell Receptor (TCR); THERAPY: Monotherapy; LEAD SPONSOR: Gadeta B.V.; CRITERIA: Inclusion Criteria: - Signed informed consent - Adult - Relapsed or refractory Multiple Myeloma as defined by the IMWG - Life expectancy ≥3 months - ECOG performance status 0 or 1 - Adequate vital organ function - Adequate bone marrow function - Toxicities from prior/ongoing therapies recovered to ≤ Grade 2 or subject's baseline - WCBP and men who can father children must be willing and able to use adequate contraception Exclusion Criteria: - Any uncontrolled medical or psychiatric disorder that would preclude participation as outlined - Pregnant or lactating women - Amyloidosis - Uncontrolled infection(s) - Active CNS disease - Previous allogeneic-HSCT - History of another primary malignancy that requires intervention beyond surveillance or that has not been in remission for at least 1 year. - Subjects that received experimental or systemic therapy < 14 days before TEG002 infusion - NYHA Class ≥ II - Patients depending on dialysis - Patients with a history of pulmonary embolism or deep vein thrombosis - T cell mediated active autoimmune disease OR any active autoimmune disease requiring immunosuppressive therapy ; PRIMARY OUTCOME: Safety determined by incidence of (S)AEs by type and grade, including the occurrence of dose-limiting toxicities (DLTs); SECONDARY OUTCOME 1: Feasibility of TEG002 generation in r/r MM patients as measured by the number of TEG002 products successfully generated in r/r MM patients

No

TRIAL NAME: Phase II - Dose-Rising; BRIEF: A Phase 2, randomized, double-blind, dose rising study to determine the safety, tolerability, and preliminary efficacy of four concentrations of SOR007 (Uncoated Nanoparticulate Paclitaxel) Ointment (SOR007) compared to SOR007 ointment vehicle applied to actinic keratosis (AK) lesions on the face twice daily for up to 28 days. ; DRUG USED: SOR007; DRUG CLASS: Non-NME; INDICATION: Actinic Keratoses; TARGET: Microtubules (Tubulin); THERAPY: Monotherapy; LEAD SPONSOR: DFB Soria, LLC; CRITERIA: Inclusion Criteria: - Signed informed consent. - Men and women with actinic keratosis. - Age 45-85. - Women who have had surgical sterilization or are post-menopausal (absence of menses for at least one year) are eligible. Women of child-bearing potential who are non-pregnant, non-nursing, and willing to avoid pregnancy during the course of the study and during the menstrual cycle following completion of their participation in the study are eligible. (Adequate contraception is defined as regular use of diaphragm with condoms, IUD with condoms, or systemic contraceptives if used for at least three months prior to enrollment in the study.) A negative pregnancy test is required as an entry criteria. Women must continue to use the method of contraceptive for at least 30 days after the last administration of study drug. - Male subjects must agree to sexual abstinence or use adequate contraception when sexually active in combination with their female partners, if they are of childbearing potential. That means the volunteer must be vasectomized or use a condom and his female partner must either be surgically sterile (hysterectomy or tubal ligation) or agree to use a reliable method of contraception with a failure rate of less than 1% per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, or non-DalKon Shield IUDs. This applies from signing of informed consent form until 90 days after the last study drug administration. Methods of contraception must have been effective for at least 30 days on the day of signing of informed consent. Male volunteers must also refrain from sperm donation from the time of singing informed consent form until 90 days after the last study drug administration. - Presence of 4-8 AK lesions total in a 25 cm2 area identified on the face through transparency mapping and photographs. The face area will be defined from hair line to jaw line. The scalp will not be included. An imaginary normal hair line will be the upper boundary for bald men. - Able to refrain from the use of all other topical medications to the facial area during the treatment period. - Considered reliable and capable of understanding their responsibility and role in the study. Exclusion Criteria: - History of allergy or hypersensitivity to paclitaxel. - Lesions that are thicker than 1 mm or larger than 9 mm will not be included in the lesion counts. - Lesions suspicious for squamous cell carcinoma, basal cell carcinoma, or melanoma will not be included in lesion counts and cannot be in the 25 cm2 area of treatment. - Abnormal pre-existing dermatologic conditions which might affect the normal course of the disease (e.g. albinism or chronic vesiculobullous disorders). - Positive urine pregnancy test in women of child-bearing potential. - Inability to use adequate birth control measures for men or women of child-bearing potential, as defined above. - Serious psychological illness. - Significant history within the past year of alcohol or drug abuse. - During the 30 day period preceding study entry: Participating in any clinical research; using topical paclitaxel for AK; using any other topical agents including but not limited to actinex, glycolic acid products, alpha-hydroxy acid products, and chemical peeling agents for the treatment of AK; using any systemic steroids or topical corticosteroids, having cryosurgery. - Use of sun lamps or sun tanning beds or booths during the 2 weeks prior to first application and until final visit. - Prior treatment with systemic paclitaxel or systemic cancer therapy within 6 months of study entry. - Medical history which, based on the clinical judgment of the Investigator implied an unlikelihood of successful completion of the study. ; PRIMARY OUTCOME: Number of Participants With Treatment Emergent Adverse Events; SECONDARY OUTCOME 1: Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve (AUC) of SOR007

No

TRIAL NAME: Phase Ib/II - BATTLE (w/Atezolizumab); BRIEF: This study will test the safety and effectiveness of a combination of investigational new drug called BL-8040 and atezolizumab to find out what effects, good or bad, this treatment has on medical condition. Atezolizumab is manufactured by Roche and is approved by FDA for other indications while BL-8040 is in late stages of clinical development. This is an investigational study. Approximately 60 patients will take part at multiple centers worldwide. It is an open-label study, which means that both subjects and the doctors will know which treatment you are receiving. All participants in the study will receive the investigational drug, BL-8040, both alone and in combination with atezolizumab. In other words, there will be no placebo (dummy drug). The duration of the treatment period of the study will be up to 2 years and will be followed by one year safety follow up. The study will consist of: - a screening period of 21 days to allow your doctor to assess your suitability for enrollment into the study - a treatment period of combination regimen of 21 day cycles for up to 2 years - a follow-up period of up to 30 days after completion of combined treatment with BL-8040 + Atezolizumab - an additional follow up period for up to one year after the completion of the treatment ; DRUG USED: Motixafortide; DRUG CLASS: New Molecular Entity (NME); INDICATION: Acute Myelogenous Leukemia (AML); TARGET: Chemokine (C-X-C motif) Receptor 4 (CXCR4); THERAPY: Combination; LEAD SPONSOR: BioLineRx, Ltd.; CRITERIA: Inclusion Criteria: AML confirmed subjects aged ≥ 60 years who have achieved complete remission (CR or CRi) after induction/consolidation Ara-C based therapy, that have MRD positive status and are not planned for stem cell transplantation. Exclusion Criteria: Subjects diagnosed with acute promyelocytic leukemia or with extramedullary AML or subjects who have achieved CR or CRi following treatment for AML. Subjects who have received treatment with hypomethylating agents. ; PRIMARY OUTCOME: Relapse Free Survival; SECONDARY OUTCOME 1:

No

TRIAL NAME: Phase II - CA224-061; BRIEF: The purpose of this study is to determine the effectiveness of relatlimab plus nivolumab, alone or in combination with various standard-of-care treatments in participants with gastric cancer (GC) or gastroesophageal junction (GEJ) adenocarcinoma that has come back or spread to other places in the body after prior therapy. ; DRUG USED: BMS-986213; DRUG CLASS: Biologic; INDICATION: Gastric Cancer; TARGET: Immune System, LAG3 (Lymphocyte-Activation Gene)/CD223, Programmed death-1 receptor (PD-1) / Programmed death ligands (PD-L1 and PD-L2); THERAPY: Combination; LEAD SPONSOR: Bristol-Myers Squibb; CRITERIA: For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: - Histologically or cytologically confirmed locally advanced or recurrent or metastatic GC or GEJ adenocarcinoma that is considered incurable by local therapies such as radiation or surgery - Evidence of progressive disease (PD) on at least one prior platinum- and fluoropyrimidine-containing chemotherapy regimen - Available tumor tissue for biomarker analysis Exclusion Criteria: - Must not have squamous cell or undifferentiated GC or GEJ - Untreated known central nervous system (CNS) metastases - Uncontrolled or significant cardiovascular disease Other protocol defined inclusion/exclusion criteria could apply ; PRIMARY OUTCOME: Overall response rate (ORR); SECONDARY OUTCOME 1: Incidence of adverse events (AEs)

No

TRIAL NAME: Phase Ib/II - Pts Awaiting Kidney Transplantation; BRIEF: Primary Objectives: - Phase 1: To characterize the safety and tolerability of isatuximab in kidney transplant candidates. - Phase 2: To evaluate the efficacy of isatuximab in desensitization of participants awaiting kidney transplantation. Secondary Objectives: - Phase 2: To characterize the safety profile of isatuximab in kidney transplant candidates. - To characterize the pharmacokinetic (PK) profile of isatuximab in kidney transplant candidates. - To evaluate the immunogenicity of isatuximab. - To assess the overall efficacy of isatuximab in desensitization of participants awaiting kidney transplantation. ; DRUG USED: Sarclisa; DRUG CLASS: Biologic; INDICATION: Kidney Transplant Rejection; TARGET: Cluster of Differentiation 38 (CD38); THERAPY: Monotherapy; LEAD SPONSOR: Sanofi; CRITERIA: Inclusion criteria: - Diagnosis of chronic kidney disease (CKD) and active candidate on the kidney donor waitlist at the time of screening. - Body mass index (BMI) </=40 kg/m^2. - Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. - Capable of giving signed informed consent. For Participants in Cohort A: active candidates on the kidney waitlist with living donor. For Participants in Cohort B: active candidates on the kidney waitlist with no living donor cleared for donation. Exclusion criteria: - Significant cardiac dysfunction. - Known active, recurrent, or chronic infection. - Active lupus or uncontrolled diabetes. - Prior treatment with rituximab within 6 months from SAR650984 administration. - Inadequate organ and bone marrow function at screening. - Pregnant or breastfeeding women or women who intend to become pregnant during participation in the study. - Known intolerance or hypersensitivity to any component of SAR650984 or pre-medications. - Participants who were not suitable for participation as judged by the Investigator. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial. ; PRIMARY OUTCOME: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs); SECONDARY OUTCOME 1: Pharmacokinetics (PK) Parameters: Concentration Observed at the End of First Intravenous Infusion (Ceoi) of Isatuximab

No

TRIAL NAME: Phase I/II - w/Yervoy and CDX-1401; BRIEF: This is a study to determine the clinical benefit (how well the drug works), safety and tolerability of combining a) varlilumab and ipilimumab and b) varlilumab, ipilimumab, CDX-1401 and poly-ICLC. The study will enroll patients with unresectable Stage III or Stage IV melanoma. ; DRUG USED: Varlilumab; DRUG CLASS: Biologic; INDICATION: Melanoma; TARGET: CD27; THERAPY: Combination; LEAD SPONSOR: Celldex Therapeutics; CRITERIA: Key Inclusion Criteria: 1. Histologic diagnosis of melanoma. 2. Unresectable Stage III or IV disease 3. Documented progressive disease based on radiographic, clinical or pathologic assessment. 4. No more than three prior anticancer regimens (BRAF/MEK inhibitors, IL-2 or investigational agents) including no more than one chemotherapy-containing regimen for advanced (recurrent, locally advanced or metastic) disease. 5. Measurable disease. 6. Life expectancy ≥ 12 weeks. 7. If of childbearing potential (male or female), agrees to practice an effective form of contraception during study treatment and for at least 70 days following last treatment. 8. Availability of tumor tissue for central laboratory analyses. Key Exclusion Criteria: 1. Previous treatment with anti-CD27 antibody, ipilimumab or other anti-CTLA-4 targeted therapies. Previous therapy with other checkpoint blockers such as anti-PD-1 or anti-PD-L1 is acceptable, unless treatment was discontinued for intolerance. 2. For patients enrolled to Phase II Cohort B: Previous administration of vaccine therapy targeting NY-ESO-1. 3. BRAF/MEK inhibitors within 2 weeks prior to first dose of study treatment. 4. Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to first dose of study treatment. 5. Monoclonal based therapies within 4 weeks and all other immunotherapy within 2 weeks prior to first dose of study treatment. 6. Systemic radiation therapy within 4 weeks, focal radiotherapy within 2 weeks and radiopharmaceuticals (strontium, samarium) within 8 weeks prior to first dose of study treatment. 7. Ocular Melanoma 8. Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancers; or any other cancer from which the patient has been disease-free for at least 3 years. 9. Active, untreated central nervous system metastases. 10. Active autoimmune disease or documented history of autoimmune disease. 11. Active diverticulitis 12. Significant cardiovascular disease including CHF or poorly controlled hypertension. ; PRIMARY OUTCOME: Phase l: Safety and tolerability of varlilumab in combination with ipilimumab as measured by incidences of drug related adverse events (AEs), serious drug related AEs, dose-limiting toxicities and laboratory test abnormalities.; SECONDARY OUTCOME 1:

No

TRIAL NAME: Phase IIb - ENCORE-PH; BRIEF: This is a multicenter, randomized, double-blind, placebo-controlled trial involving subjects with NASH cirrhosis and severe portal hypertension (defined as HVPG ≥12 mmHg as determined by the central reader assigned to this study). Upon successful screening, subjects will be randomized to receive either emricasan 50 mg BID, 25 mg BID, or 5 mg BID or matching placebo BID. ; DRUG USED: Emricasan; DRUG CLASS: New Molecular Entity (NME); INDICATION: Non-Alcoholic Steatohepatitis (NASH); TARGET: Caspases; THERAPY: Monotherapy; LEAD SPONSOR: Histogen; CRITERIA: Inclusion Criteria: - Male or female subjects 18 years or older, able to provide written informed consent and able to understand and willing to comply with the requirements of the study. - Cirrhosis due to NASH with exclusion of other causes of cirrhosis (e.g. chronic viral hepatitis, alcoholic liver disease, etc.) - Compensated cirrhosis OR Decompensated cirrhosis with no more than 1 prior significant decompensating event - Severe portal hypertension defined as HVPG ≥12 mmHg - Subjects who are on NSBB, nitrates, diuretics, lactulose, rifaximin, or statins must be on a stable dose for at least 3 months prior to Day 1 - Willingness to utilize effective contraception (for both males and females of childbearing potential) from Screening to 4 weeks after the last dose of study drug Exclusion Criteria: - Evidence of severe decompensation - Severe hepatic impairment defined as a Child-Pugh score ≥10 - ALT (alanine transaminase) > 3 times upper limit of normal (ULN) or AST (aspartate transaminase) >5 times ULN during screening - Estimated creatinine clearance <30 mL/min - Prior transjugular intrahepatic portosystemic shunt or other porto-systemic bypass procedure - Known portal vein thrombosis - Symptoms of biliary colic, e.g. due to symptomatic gallstones, within the last 6 months, unless resolved following cholecystectomy - Current use of medications that are considered inhibitors of OATP1B1 and OATP1B3 transporters - Alpha-fetoprotein >50 ng/mL - History or presence of clinically concerning cardiac arrhythmias, or prolongation of screening (pre-treatment) QTcF interval of >500 msec - History of or active malignancies, other than those successfully treated with curative intent and believed to be cured - Prior liver transplant - Change in diabetes medications or vitamin E within 3 months of screening - Uncontrolled diabetes mellitus (HbA1c >9%) within 3 months of screening - Significant systemic or major illness other than liver disease - HIV infection - Use of controlled substances (including inhaled or injected drugs) or non-prescribed use of prescription drugs within 1 year of screening - If female: planned or known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding - Previous treatment with emricasan or active investigational medication (except methacetin) in a clinical trial within 3 months prior to Day 1 ; PRIMARY OUTCOME: Mean Change in Hepatic Venous Pressure Gradient (HVPG); SECONDARY OUTCOME 1: Improvement of HVPG Response Using a 20% Reduction From Baseline

No

TRIAL NAME: Phase I/II - KEYNOTE-0036 (w/Utomilumab); BRIEF: This is a safety, pharmacokinetic and pharmacodynamic study designed to estimate the maximum tolerated dose (MTD), and determine the Recommended Phase 2 Dose (RP2D) of PF-05082566, a 4-1BB agonist monoclonal antibody (mAb), in combination with MK-3475, a PD-1 inhibitor in patients with solid tumors. ; DRUG USED: Keytruda; DRUG CLASS: Biologic; INDICATION: Solid Tumors; TARGET: Immune System, Programmed death-1 receptor (PD-1) / Programmed death ligands (PD-L1 and PD-L2); THERAPY: Monotherapy; LEAD SPONSOR: Pfizer; CRITERIA: Inclusion Criteria: - Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy which has progressed on standard therapy or for which no standard therapy is available. - Measurable disease per RECIST v1.1. - Adequate bone marrow, renal and liver functioning Exclusion Criteria: - CNS primary malignancies, active seizure disorder or spinal cord compression, or carcinomatous meningitis. - History of any of the following toxicities associated with a prior immunotherapy: - Grade 3 immune mediated adverse event that was considered related to previous immunotherapy and required immune suppressive therapy; - Grade 2 hepatic function related adverse event that persisted more than 1 week, was considered related to immunotherapy, or required treatment discontinuation or immunosuppressive therapy - Any of the following within the 12 months prior to registration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and 6 months for deep vein thrombosis or pulmonary embolism. - History of or known presence of extensive, disseminated/bilateral or Grade 3 or 4 interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, or pulmonary fibrosis, but not including a history of prior radiation pneumonitis. Patients with clinically significant lung disease requiring oxygen therapy (eg, COPD). ; PRIMARY OUTCOME: Number of Participants With Dose-Limiting Toxicities (DLT) of PF-05082566 in Combination With MK-3475; SECONDARY OUTCOME 1: Number of Subjects With Serious Adverse Events (SAEs) and Treatment Emergent Adverse Events (TEAEs) by Maximum CTCAE Grade (All Causalities)

Yes

TRIAL NAME: Phase III - AUTOMATIX; BRIEF: Primary Objective: To demonstrate the non-inferiority of the MyStar DoseCoach (Long-acting Insulin Glargine Titration Meter) device-supported treat-to-target regimen relative to a routine titration regimen in the percentage of patients reaching glycemic target, ie, with a mean fasting self-monitored plasma glucose (FSMPG) value within the target range of 90-130 mg/dL (5.0-7.2 mmol/L) without a severe hypoglycemic episode during the 16-week on-treatment period. Secondary Objective: To assess the efficacy, safety, and adherence/satisfaction of MyStar DoseCoach ; DRUG USED: Toujeo; DRUG CLASS: Non-NME; INDICATION: Diabetes Mellitus, Type II; TARGET: Insulin Receptor; THERAPY: Monotherapy; LEAD SPONSOR: Sanofi; CRITERIA: Inclusion criteria : - Patients with type 2 diabetes mellitus diagnosed at least one year before the screening visit. - Patients who are insulin naïve (and considered by the investigator to be appropriate candidates for basal insulin therapy), or treated with basal insulin as their only insulin. - HbA1c between 7.5% and 11% (inclusive) at screening. - Fasting SMPG >130 mg/dL at first screening and FSMPG >130 mg/dL at randomization. - Signed informed consent. Exclusion criteria: - Aged <18 years. - Diabetes other than type 2 diabetes mellitus. - MyStar DoseCoach device is not appropriate for the patient or use of device is otherwise contraindicated (in the opinion of the Investigator). - Conditions/situations that are contraindications or off-label use according to Summary of Product Characteristics (SmPCs) of Oral Anti-Diabetes Drugs (OADs) and/or GLP-1 receptor agonists when applicable (prescribed), or insulin glargine and as defined in the national product label. - Patients not on stable dose of glucose lowering therapy including OADs, GLP-1 receptor agonists, or basal insulin therapy, for the last 3 months (stable basal insulin therapy defined as maximum change in insulin dose of +/- 20%). - Patients using mealtime insulin (short acting analogue, human regular insulin, or premix insulin) for more than 10 days in the last 3 months before screening visit. - Patients with hypoglycemia unawareness. - Patients with severe hypoglycemia in the past 90 days. - Hospitalization in the past 30 days. - Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one week or more within 90 days prior to the time of screening. - Unable to meet specific protocol requirements (eg, inability to perform blood glucose measurements, manage their own insulin glargine administration, or deemed unlikely to safely manage titration based on guidance by their health care provider or HCP, etc.), because of a medical condition or because the patient is under legal guardianship. - Patients with cognitive disorders, dementia, or any neurologic disorder that would affect a patient's ability to participate in the study, including the inability to understand study requirements or to give complete information about adverse symptoms. - Conditions/situations such as: - Patients with conditions/concomitant diseases precluding their safe participation in this study (eg, active malignant tumor, major systemic diseases, presence of clinically significant diabetic retinopathy or presence of macular edema likely to require treatment within the study period, etc.), - Patients unable to fully understand study documents and to complete them. Patients who have a caregiver together with whom they can fulfill all study requirements are eligible, - Patient is the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol. - Within the last 3 months prior to screening: history of myocardial infarction, unstable angina, acute coronary syndrome, revascularization procedure, or stroke requiring hospitalization. - Severe or uncontrolled Congestive Heart Failure (New York Heart Association [NYHA] functional classification III and IV); or inadequately controlled hypertension at the time of screening with a resting systolic or diastolic blood pressure >180 mmHg or >95 mmHg, respectively. - Pregnant or breast-feeding women or women who intend to become pregnant during the study period as glycemic control may be unstable and insulin doses may be variable during this period. - Women of childbearing potential (premenopausal, not surgically sterile for at least 3 months prior to the time of screening) must use an effective contraceptive method throughout the study. Effective methods of contraception include barrier methods (in conjunction with spermicide), hormonal contraception, or use of an intrauterine device (IUD) or intrauterine hormone-releasing system (IUS). The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial. ; PRIMARY OUTCOME: Percentage of patients reaching fasting SMPG target range 90-130 mg/dL (5.0-7.2 mmol/L) at Week 16 (mean of the last 5 readings recorded over the last 2 weeks) without a severe hypoglycemic episode during the 16-week on-treatment period; SECONDARY OUTCOME 1: Percentage of patients reaching fasting SMPG target range of 90-130 mg/dL (5.0-7.2 mmol/L), (mean of the last 5 readings recorded over the last 2 weeks) without severe and/or confirmed hypoglycemic events

Yes

TRIAL NAME: Phase III - ENLIGHTEN-1; BRIEF: This study will evaluate the efficacy of ALKS 3831 in adult subjects with acute exacerbation of schizophrenia. ; DRUG USED: Lybalvi; DRUG CLASS: New Molecular Entity (NME); INDICATION: Schizophrenia; TARGET: Alpha 1 Adrenergic Receptor , Dopamine 1 (D1) Receptor, Dopamine 2 (D2) Receptor, Dopamine 4 (D4) Receptor, Histamine H1 Receptor (HRH1), Opioid receptors, Serotonin 5-HT2A receptor, Serotonin 5-HT2C receptor; THERAPY: Monotherapy; LEAD SPONSOR: Alkermes, Inc.; CRITERIA: Inclusion Criteria: - Has a body mass index (BMI) of 18.0 - 40.0 kg/m^2 - Meets criteria for the diagnosis of schizophrenia - Resides in a stable living situation when not hospitalized - Is willing and able to provide government-issued identification - Additional criteria may apply Exclusion Criteria: - Has had a psychiatric hospitalization for more than 30 days during the 90 days before screening - Subject initiated first antipsychotic treatment within the past 12 months, or <1 year has elapsed since the initial onset of active-phase of schizophrenia symptoms - Subject poses a current suicide risk - Subject has a history of treatment resistance - Subject has a history of poor or inadequate response to treatment with olanzapine - Subject requires or has had electroconvulsive therapy (ECT) treatment in the 2-month period prior to screening - Subject has a diagnosis of moderate or severe alcohol or drug use disorder - Subject has a positive urine drug screen for opioids, amphetamine/methamphetamine, phencyclidine, or cocaine at screening - Additional criteria may apply ; PRIMARY OUTCOME: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4; SECONDARY OUTCOME 1: Change From Baseline in Clinical Global Impressions-Severity (CGIS) Score at Week 4

Yes

TRIAL NAME: Phase Ib - Lupus Nephritis; BRIEF: The sponsor electively terminated the study because the risk mitigation measures, deemed necessary after an unforeseen safety event, could not be effectively implemented within this protocol while maintaining study timelines within a reasonable time frame. ; DRUG USED: Atacicept; DRUG CLASS: Biologic; INDICATION: Lupus Nephritis; TARGET: APRIL, B-cell activating factor (BAFF); THERAPY: Monotherapy; LEAD SPONSOR: EMD Serono; CRITERIA: Inclusion Criteria: - Male or female subjects, ≥ 18 years of age, who provide written informed consent - Subjects must have a diagnosis of SLE satisfying ≥ 4 of 11 ACR criteria, and must have had a renal biopsy during screening or within the previous 18 months demonstrating class III (A or A/C), IV (A or A/C), V, or concomitant III/V or IV/V LN as defined by the International Society of Nephrology/Renal Pathology Society (ISN/RPS). - Subjects must have a urine protein: creatinine ratio ≥ 2 mg/mg (≥ 226.2 mg/mmol), and either a positive test for antinuclear antibody (ANA) (HEp-2 ANA ≥ 1:80) and/or anti-double stranded deoxyribonucleic acid (dsDNA) (≥ 30 IU/mL) at screening. - Subjects must have started induction therapy for LN at least 5 months prior to Trial Day 1, be considered to have received continuous treatment for LN during the 5 months prior to Trial Day 1, and have received a stable dose of MMF ≥ 1 g/day, with or without corticosteroids, for at least 8 weeks prior to Trial Day 1. Exclusion Criteria: - Recent changes in immunosuppressant, ACD inhibitors for ARBs - Use of azathioprine, cyclosporine, tacrolimus, or cyclophosphamide or other biologics within 8 weeks prior to Trial Day 1. - Serum IgG < 6 g/L - Estimated Glomerular Filtration Rate (GFR) ≤ 30 mL/min per 1.73 m2 - History of Demyelinating Disease - Significant Hematuria and/or Proteinuria due to a reason(s) other than LN. Evaluation should be done according to the local standard of care - Breast feed or pregnancy - Legal Incapacity or limited legal capacity ; PRIMARY OUTCOME: The nature (preferred terms) and incidence of AEs; SECONDARY OUTCOME 1: The nature (preferred terms) and incidence of AEs

No

TRIAL NAME: Phase III - NOCT; BRIEF: This study evaluates the efficacy, safety and tolerability of NER1006 versus Trisulfate Solution (TS) in adult patients requiring bowel cleansing prior to any procedure that requires a clean bowel, using a 2-Day evening/morning Split-Dosing regimen. Approximately 540 patients will be randomised with the aim of achieving a minimum of 245 patients in each of the 2 groups. ; DRUG USED: Plenvu; DRUG CLASS: Non-NME; INDICATION: Colon Cleansing/Laxatives; TARGET: Osmosis/Osmotic Pressure; THERAPY: Monotherapy; LEAD SPONSOR: Norgine; CRITERIA: Inclusion Criteria: - Written informed consent - Male and female outpatients and inpatients aged ≥18 to ≤85 years undergoing a screening, surveillance, or diagnostic colonoscopy - Females of child bearing potential must have a negative pregnancy test at Screening and at Visit 2 and must be practising one of the following methods of birth control and agree to continue with the regimen throughout the study period: Oral, implantable, or injectable contraceptives (for a minimum of three months before study entry) in combination with a condom; Intrauterine device in combination with a condom; Double barrier method (condom* and occlusive cap [diaphragm or cervical/vault caps] with spermicidal foam/gel/film/cream/suppository) - Willing, able and competent to complete study and comply with instructions. Exclusion Criteria: - Patients with past history within last 12 months or current episode of severe constipation (requiring repeated use of laxatives/enema or physical intervention before resolution), known or suspected ileus, gastrointestinal obstruction, gastric retention, bowel perforation, toxic colitis or megacolon. - Patients with ongoing severe acute Inflammatory Bowel Disease (IBD). - Patients who have had previous significant gastrointestinal surgeries, including colonic resection, sub-total colectomy, abdomino-perineal resection, de-functioning colostomy, Hartmann's procedure and de-functioning ileostomy or other similar surgeries involving structure and function of the small or large colon. - Regular use of laxatives or colon motility altering drugs in the last month (i.e. more than 2-3 times per week) and/or laxative use within 72 hours prior to administration of the preparation. - Patients with active intestinal bleeding episodes or with a clinically significant low hemoglobin level <9 g/dL for women and <11 g/dL for men at screening. - Known glucose-6-phosphate dehydrogenase (G6PD) deficiency. - Known phenylketonuria. - Known hypersensitivity to polyethylene glycols, ascorbic acid and sulfates (not including sulfa-based products) or any other component of the investigational product or comparator. - Past history within the last 12 months or evidence of any on-going clinically relevant electrocardiogram (ECG) abnormalities (e.g. arrhythmias). - History of uncontrolled hypertension with systolic blood pressure >170 mmHg and diastolic blood pressure >100 mmHg. - Patients with cardiac insufficiency NYHA grades III or IV. - Patients with moderate to severe renal insufficiency (i.e. with GFR, <60 mL/min/1.73m2). - Patient with serum albumin < 3.4 g/dL. - Patients with liver disease of grades B and C according to the Child Pugh classification. - Patients suffering from dehydration at screening as evaluated by the Investigator from physical examination and laboratory investigations. - Patients with clinically significant electrolyte abnormalities, whether pre-existing or noted at screening, such as hypernatremia, hyponatremia, hyperphosphatemia, hypermagnesemia, hypokalemia, hypocalcaemia, dehydration, or those secondary to the use of diuretics or angiotensin converting enzyme (ACE) inhibitors. - Patients with any other clinically significant hematological parameters including coagulation profile at screening. - Patients with impaired consciousness that might predispose them to pulmonary aspiration. - Patients undergoing colonoscopy for foreign body removal and/or decompression. - Patients who are pregnant or lactating, or intending to become pregnant during the study. - Clinically relevant findings on physical examination based on the Investigator's judgment. - History of drug or alcohol abuse within the 12 months prior to dosing. - Concurrent participation in an investigational drug or device study or participation within three months of study entry. - Patients who, in the opinion of the Investigator, should not be included in the study for any reason, including inability to follow study procedures, e.g. cognitively impaired, debilitated or fragile patients. - Patients who are ordered to live in an institution on court or authority order. ; PRIMARY OUTCOME: Number of Patients With Successful Bowel Cleansing (Overall Colon); SECONDARY OUTCOME 1: Adenoma Detection Rate (Colon Ascendens)

Yes

TRIAL NAME: Phase II (Active/Intermediate Uveitis); BRIEF: This study was performed to evaluate the efficacy and safety of AIN457 for patients with active uveitis that requires systemic immunosuppression. ; DRUG USED: Cosentyx; DRUG CLASS: Biologic; INDICATION: Uveitis (Ophthalmology); TARGET: IL-17 (Interleukin 17); THERAPY: Combination; LEAD SPONSOR: Novartis Pharmaceuticals; CRITERIA: Inclusion criteria: - Active uveitis (i.e., uveitis that is not in remission). - Intermediate uveitis, posterior uveitis, or panuveitis must be sufficiently severe that systemic immunosuppression is indicated. Exclusion criteria: - Active infection. - Weight must not be greater that 120kg. Other protocol-defined inclusion/exclusion criteria may apply ; PRIMARY OUTCOME: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Who Died; SECONDARY OUTCOME 1: Number of Responders in Cohort 1, 2, 3 and 6 at Day 57

Yes

TRIAL NAME: Phase I - VAR0113 (Stanford); BRIEF: The purpose of this study is to assess the safety and tolerability of Hu5F9-G4 in participants with solid tumors. ; DRUG USED: Magrolimab; DRUG CLASS: Biologic; INDICATION: Solid Tumors; TARGET: Cluster of Differentiation 47 (CD47), Immune System; THERAPY: Monotherapy; LEAD SPONSOR: Gilead Sciences; CRITERIA: Inclusion Criteria: Patients with histologically or cytologically confirmed advanced solid malignancy or Lymphoma Relapsed or refractory disease after at least 1 prior systemic treatment for the primary malignancy and not a candidate for other curative treatment. Adequate hematologic status Adequate coagulation function Adequate hepatic function Adequate renal function Exclusion Criteria: Known primary tumors of central nervous system disease Known active brain metastases Known cardiopulmonary disease ; PRIMARY OUTCOME: Safety and Tolerability of Hu5F9-G4; SECONDARY OUTCOME 1:

Yes

TRIAL NAME: Phase I - Adolescents; BRIEF: The trial is a Phase 1 Single Dose PK Study in Adolescent Subjects with Fragile X syndrome (FXS) or Angelman syndrome (AS). - The primary objective of the study is to evaluate the pharmacokinetics (PK) of OV101 following a single 5 mg dose of OV101 in adolescents with FXS or AS. - Secondary objectives are to determine the safety and tolerability of a single 5 mg dose of OV101 in adolescents with FXS or AS. ; DRUG USED: OV101; DRUG CLASS: New Molecular Entity (NME); INDICATION: Fragile X Syndrome; TARGET: GABA-A Receptor; THERAPY: Monotherapy; LEAD SPONSOR: Ovid Therapeutics Inc.; CRITERIA: Inclusion Criteria: 1. Adolescents with confirmed clinical and previous molecular diagnosis of FXS or AS, age between 13 to 17 years, inclusive. 2. Subjects must assent to participation in the study (if appropriate), have a parent or legal guardian/representative capable of providing informed consent on behalf of the subject, and commit to participate in all assessments described in the protocol. 3. Subjects must be receiving a stable dose of concomitant medications 4. Subjects should be able to complete study assessments. 5. Subjects who are non-sterile must agree to either remain completely abstinent or to use two effective contraceptive methods from screening until 7 days after the last dose of study treatment. 6. Subjects must have a parent or other reliable caregiver who agrees to accompany the subject at all study visits and provide information about the subject as required by the study protocol, and ensure compliance with the protocol. Exclusion Criteria: 1. Inability to swallow a capsule. 2. Poorly controlled seizures 3. Clinically significant abnormal ECG at the time of screening. 4. Positive result on serum or urine pregnancy test for women of child-bearing potential (have experienced menarche) who are not using a dual method of contraception (e.g., condoms plus oral contraceptives), with abstinence being an accepted method. 5. Allergy to gaboxadol or any excipients 6. Concomitant cardiovascular, respiratory, liver, renal, or hematologic diseases of a degree that would limit participation in the study 7. History of suicidal behavior or considered a high suicidal risk by the investigator. 8. Any medical, psychological, social disorder(s), or other conditions - including seizure disorder ; PRIMARY OUTCOME: Measurement of maximum plasma concentration achieved following a single dose of OV101; SECONDARY OUTCOME 1: Safety parameters, adverse events, absolute values and changes over time of hematology, clinical chemistry, urinalysis, vital signs, electrocardiogram (ECG)

Yes

TRIAL NAME: Phase II - VANGARD; BRIEF: This is a multicenter, randomized, double-blind, parallel group study to investigate the efficacy of pemziviptadil (PB1046) by improving the clinical outcomes in hospitalized COVID-19 patients at high risk for rapid clinical deterioration, acute respiratory distress syndrome (ARDS) and death. The study will enroll approximately 210 hospitalized COVID-19 patients who require urgent decision-making and treatment at approximately 20 centers in the United States. ; DRUG USED: Vasomera; DRUG CLASS: New Molecular Entity (NME); INDICATION: COVID-19 Treatment; TARGET: Vasoactive Intestinal Peptide (VIP) Receptor; THERAPY: Monotherapy; LEAD SPONSOR: PhaseBio Pharmaceuticals Inc.; CRITERIA: Inclusion Criteria: 1. Written or witnessed verbal informed consent from patient or remote legal authorized representative (LAR) or remote family member as permitted by governing local or central Institutional Review Board (IRB)/independent Ethic Committee (IEC). 2. Male or female 18-85 years old hospitalized COVID-19 patients (positive local SARS-CoV2 test) 3. Receiving oxygen (O2) by face mask or nasal cannula/prongs and/or with elevated markers of cardiac injury or dysfunction (hsTnI or NT-proBNP) as assessed by local testing Exclusion Criteria: Subjects will be excluded from the study if they meet any of the following criteria: 1. Patients considered unsalvageable or expected to expire within 24 hours 2. On mechanical ventilation or imminent need for mechanical ventilation expected in the next 24 hours 3. Evidence of acute end-organ injury in 2 or more organ systems (not including cardiac or pulmonary), such as, renal, hepatic, or CNS injury 4. Receiving another investigational therapy for treatment or prevention of COVID-19-related hypoxemic respiratory failure or ARDS other than antiviral therapy 5. Systolic blood pressure (SBP) < 95 mmHg and/or diastolic blood pressure (DBP) < 50 mmHg or overt symptomatic hypotension during screening 6. Resting heart rate > 110 BPM (beats per minute) during screening 7. Severe chronic renal failure as measured by the estimated glomerular filtration rate (eGFR) of < 30 mL/min/1.73m2 using the local laboratory calculation of eGFR. 8. Significant liver dysfunction as measured by any one of the following at screening: - ALT (Alanine transaminase) > 3.0 times ULN (upper limit of normal) - AST (Aspartate transaminase) > 3.0 times ULN - Serum bilirubin ≥ 1.6 mg/dL 9. Any in-patient surgical procedure or hospitalization (defined as > 23 hours) within 30 days of subject screening except for prior hospitalization for COVID-19 10. Known hypersensitivity to study drug or any of the excipients of the drug formulation 11. Pregnant or lactating female subjects 12. Any other condition which, in the opinion of the Investigator, would place the subject at increased risk or would preclude obtaining informed consent or confound the objectives of study ; PRIMARY OUTCOME: Time to clinical recovery from initiation of pemziviptadil (PB1046); SECONDARY OUTCOME 1: Time to clinical recovery (being well enough for hospital discharge or returning to normal baseline activity level prior to discharge)

No

TRIAL NAME: Phase III - EMPERIAL-Reduced; BRIEF: The primary objective of the study is to evaluate the effect of empagliflozin 10 mg versus placebo on exercise ability using the 6 minute walk test in patients with chronic HF with reduced ejection fraction (LVEF ≤ 40%) Secondary objectives are to assess Patient-Reported Outcome (PRO) ; DRUG USED: Jardiance; DRUG CLASS: New Molecular Entity (NME); INDICATION: Chronic Heart Failure - Reduced Ejection Fraction (Chronic HFrEF); TARGET: SGLT; THERAPY: Monotherapy; LEAD SPONSOR: Boehringer Ingelheim; CRITERIA: Inclusion Criteria: - Of full age of consent (according to local legislation, usually ≥ 18 years) at screening. - Male or female patients. Women of childbearing potential (WOCBP)1 must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information. - Signed and dated written informed consent in accordance with ICHGCP and local legislation prior to admission to the trial - 6MWT distance ≤350 m at screening and at baseline. - Patients with chronic HF diagnosed for at least 3 months before Visit 1 and currently in NYHA class II-IV - Chronic HF with reduced EF defined as LVEF ≤ 40 % as per echocardiography at Visit 1 as per local reading (obtained under stable condition). - Elevated NT-proBNP > 450 pg/ml for patients without atrial fibrillation (AF) OR NTproBNP > 600 pg/ml for patients with AF as analysed at the Central laboratory at Visit 1 - Patients must be clinically stable and on appropriate and stable dose of medical therapy for HF (such as ACEi, ARB, β-blocker, oral diuretics, MRA, ARNI, ivabradine), consistent with prevailing CV guidelines, stable for at least 4 weeks prior to Visit 1(screening) with the exception of diuretics which must have been stable for at least two weeks prior to Visit 1. The investigator must document the reason in case the patient is not on such medication or if not on target dose of any heart failure medication as per local guidelines. - Clinically stable at randomization with no signs of heart failure decompensation (as per investigator judgement). - Appropriate use of medical devices such as cardioverter defibrillator (ICD) or a cardiac resynchronization therapy (CRT) consistent with prevailing local or international CV guidelines, and if a device is required, it must have been implanted for at least 3 months prior to visit 1 for CRT and 1 month prior to visit 1 for ICD. Exclusion Criteria: - Myocardial infarction (increase in cardiac enzymes in combination with symptoms of ischaemia or newly developed ischaemic ECG changes), coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or TIA in past 90 days prior to Visit 1 - Acute decompensated HF (exacerbation of chronic HF) requiring intravenous (i.v.) diuretics, i.v. inotropes or i.v. vasodilators, or left ventricular assist device within 4 weeks prior to Visit 1, and/or during screening period until Visit 2 - Previous or current randomisation in another Empagliflozin Heart Failure trial (i.e. studies 1245.110, 1245.121, 1245-0167) - Type 1 Diabetes Mellitus (T1DM) - Impaired renal function, defined as eGFR < 20 mL/min/1.73 m2 (CKD-EPIcr) or requiring dialysis, as determined at Visit 1 - Symptomatic hypotension or a SBP < 100 mmHg at Visit 1 or 2 - Systolic blood pressure (SBP) ≥ 180 mmHg at Visit 1 or 2, or SBP >160mmHg at both Visit 1 and 2 - Atrial fibrillation or atrial flutter with a resting heart rate >110 bpm documented by ECG at Visit 1 (Screening) - Unstable angina pectoris in past 30 days prior to Visit 1 - Largest distance walked in 6 minutes (6MWTD) at baseline <100m. - Any presence of condition that precludes exercise testing such as: - claudication, - uncontrolled (according to investigator judgement) bradyarrhythmia or tachyarrhythmia, - significant musculoskeletal disease, - primary pulmonary hypertension, - severe obesity (body mass index ≥40.0 kg/m2), - orthopedic conditions that limit the ability to walk (such as arthritis in the leg, knee or hip injuries) - amputation with artificial limb without stable prosthesis function for the past 3 months - Any condition that, in the opinion of the investigator, would contraindicate the assessment of 6MWT - Patients in a structured (according to Investigator judgement) exercise training program in the 1 month prior to screening or planned to start one during the course of this trial. - Planned implantation of ICD or CRT during the course of the trial. - Treatment with i.v. iron therapy or erythropoietin within 3 months prior to screening - Treatment with i.v. iron therapy or erythropoietin within 3 months prior to screening - Further exclusion criteria applies ; PRIMARY OUTCOME: Change From Baseline to Week 12 in Exercise Capacity as Measured by the 6-Minutes-Walking-Test (6MWT) Distance; SECONDARY OUTCOME 1: Change From Baseline to Week 12 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (TSS)

Yes

TRIAL NAME: Phase II - LCP-AtorFen-2001; BRIEF: The current study is designed to test the efficacy, safety and tolerability of LCP-AtorFen, a combination of atorvastatin and fenofibrate. ; DRUG USED: AtorFen; DRUG CLASS: Non-NME; INDICATION: Dyslipidemia / Hypercholesterolemia; TARGET: HMG CoA Reductase (HMGR), PPAR alpha; THERAPY: Monotherapy; LEAD SPONSOR: Veloxis Pharmaceuticals; CRITERIA: Inclusion Criteria: 1. A diagnosis of dyslipidemia (non-HDL-C >130 mg/dL and Triglycerides > or equal to 150 mg/dL and < or equal to 500 mg/dL). 2. Subject may be currently on a statin or other lipid-lowering therapy but must be willing and able to washout for 8 weeks if on a fibrate or high-dose niacin, 6 weeks if on a statin or low-dose niacin per day, or 4 weeks if on a bile acid sequestrant, ezetimibe, or >1000 mg of fish oil per day. 3. Other inclusion criteria might apply Exclusion Criteria: 1. TGs > 500 mg/dL. 2. History of coronary heart disease (CHD), transient ischemic attacks, stroke or revascularization procedure in the six months prior. 3. Presence of an aortic aneurysm or resection of an aortic aneurysm within six months. 4. Poorly controlled diabetes mellitus (glycosylated hemoglobin >8.0% )or diabetes mellitus requiring insulin therapy. 5. Known lipoprotein lipase impairment or deficiency or Apo C-II deficiency or familial dysbetalipoproteinemia. 6. History of pancreatitis. 7. Known allergy or sensitivity to statins or fibrates. 8. Poorly controlled hypertension. 9. Other exclusion criteria might apply. ; PRIMARY OUTCOME: Percent Changes From Baseline to End-of-treatment in Non-HDL Cholesterol, HDL Cholesterol, and Triglycerides by LCP-AtorFen Versus Atorvastatin Monotherapy; SECONDARY OUTCOME 1: Percent Changes From Baseline to End-of-treatment in Non-HDL, HDL and LDL Cholesterol by LCP-AtorFen Versus Fenofibrate Monotherapy

No

TRIAL NAME: Phase III - PA-CL-CHINA-01; BRIEF: This study evaluates the efficacy of PA21 in comparison with sevelamer carbonate (Renvela®) in lowering and maintaining serum phosphorus in adult Chinese subjects with CKD on dialysis after 12 weeks of treatment. ; DRUG USED: Velphoro; DRUG CLASS: Non-NME; INDICATION: Hyperphosphatemia; TARGET: Phosphate; THERAPY: Monotherapy; LEAD SPONSOR: Vifor Fresenius Medical Care Renal Pharma; CRITERIA: Inclusion Criteria: 1. Chinese subjects receiving either maintenance haemodialysis (HD) or peritoneal dialysis (PD) for at least 12 weeks prior to screening. No home HD or nocturnal HD (overnight stay at site) will be allowed 2. Subjects with a history of hyperphosphataemia (HP). 3. Subjects with serum phosphorus levels >5.5 mg/dl (>1.78 mmol/l) at screening or during the washout period. 4. Male and female adult subjects (aged ≥18 years at time of consent). 5. Subjects with the ability to understand the requirements of the study and abide by the study restrictions, and who agree to return for the required assessments (in the Investigator's opinion). 6. Subject (or legally acceptable representative) has provided the appropriate written informed consent. Subject must provide written informed consent before any study-specific procedures are performed including screening procedures. Exclusion Criteria: 1. Subjects with intact parathyroid hormone (iPTH) levels >800 ng/l (>800 pg/ml or 88 pmol/l) at screening. Subjects with iPTH >600 ng/l (>600 pg/ml or 66 pmol/l) at screening must be considered stable (in the Investigator's opinion). 2. Subjects with planned or expected parathyroidectomy within the next 6 months (in the Investigator's opinion). 3. Subjects on peritoneal dialysis (PD) with a history of peritonitis in the last 3 months or ≥3 episodes in the last 12 months. 4. Subjects with serum total calcium >10.5 mg/dl (>2.6 mmol/l) or <7.6 mg/dl (1.9 mmol/l) at screening. 5. Subjects with: - Any history of major gastrointestinal (GI) surgery likely to influence the outcome of treatment with PBs - Clinically significant, active GI disorders (e.g., active peptic ulcer, Crohn's disease, colitis ulcerative, irritable bowel syndrome, intestinal motility disorder (symptomatic gastroparesis (during treatment or untreated), intestinal obstruction, moderate/severe constipation (including persistent symptoms with regular use of laxatives or enemas and limitations in activities of daily living), intestinal pseudo-obstruction, megacolon, mechanical obstruction)) or any GI disorders under medical treatment. - Clinically significant, active hepatic disorders or any hepatic disorder under medical treatment 6. Subjects currently with (in the Investigator's opinion): - Swallowing difficulties/dysphagia - Estimated life expectancy of less than 12 months - Anticipated renal transplantation during study participation 7. Subjects with known seropositivity to human immunodeficiency virus or positive HIV test at screening. 8. Subjects with active/current fulminant hepatitis B infections and/or hepatitis C virus ribonucleic acid positivity at screening. 9. Subjects with a history of haemochromatosis or other iron accumulation disorders that might lead to iron overload. 10. Subjects with serum ferritin >800 mcg/l (1,797.6 pmol/l) or transferrin saturation (TSAT) >50% at screening. 11. Subjects with raised alanine aminotransferase or aspartate aminotransferase >3 times the upper limit of the normal range at screening. 12. Subject is taking any prohibited medication(s) which cannot be stopped at least one week before study treatment start. Prohibited medications include: oral calcium supplements, any drugs/agents having a phosphate binding action that contain aluminium, magnesium or calcium (apart from hyperkalaemia drugs), phosphate binders in addition to sevelamer carbonate), nicotinamide, oral iron products, oral vitamins containing iron and other oral iron containing supplements (See Section 7.7). 13. Subject has known hypersensitivity and/or intolerance to any of the study products to be administered. 14. Subject has previously been randomised into this study. 15. Subject is currently enrolled in or has completed any other investigational device or drug study <30 days prior to screening, or is receiving other investigational agent(s). 16. Subjects who are pregnant (e.g., positive human chorionic gonadotropin test) or breastfeeding. 17. Subjects of childbearing potential, not using adequate contraceptive precautions must agree to use a highly effective method of birth control during the study and for 1 month after the last dose of study medication. 18. Subject has a history of drug or alcohol abuse within 2 years prior to screening. 19. Subject has a significant medical conditions or anticipated need for major surgery during the study, which (in the Investigator's opinion), may be associated with increased risk to the subject, or may interfere with study assessments or outcomes, or the ability to provide informed consent or comply with study procedures. ; PRIMARY OUTCOME: Serum phosphorus (mmol/l ); SECONDARY OUTCOME 1: Serum phosphorus (mmol/l )

Yes

TRIAL NAME: Phase I/II - APPEASE (HCI); BRIEF: This is an open label nonrandomized Phase I/ IIA trial designed to assess the safety, tolerability, and efficacy of apatinib in combination with pembrolizumab. Phase I will assess the safety of combining increasing oral daily doses of apatinib with a fixed dose of IV pembrolizumab every three weeks and will determine the RP2D (Recommended Phase 2 Dose). Phase II will assess the efficacy of the RP2D of apatinib in combination with pembrolizumab and provide additional safety and tolerability data in three disease-specific cohorts ; DRUG USED: Rivoceranib; DRUG CLASS: New Molecular Entity (NME); INDICATION: Solid Tumors; TARGET: VEGF Receptor (VEGFR); THERAPY: Combination; LEAD SPONSOR: University of Utah; CRITERIA: Inclusion Criteria: - Male or female subject aged ≥ 18 years. - One of the following advanced solid malignancies which qualifies for standard of care pembrolizumab treatment per FDA approval: - Locally advanced or metastatic urothelial carcinoma that has progressed during or following platinum-based chemotherapy or within 12 months of neoadjuvant/adjuvant platinum-based therapy. Patients may have received any amount of platinum-based therapy. - Unresectable or metastatic MSI-H or dMMR solid tumors that have progressed during or following prior treatment and have no satisfactory alternative treatment options (including MSI-H or dMMR colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan). - Recurrent locally advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma expressing PD-L1 (as determined by an FDA-approved test) that have progressed on or after two or more systemic therapies, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy. - Patients must have available and be willing to provide formalin fixed paraffin embedded tissue sample from archival tissue (patients who can't provide archival tissue will be offered an optional biopsy; lack of tissue will not be exclusionary). - Have measurable disease based on RECIST 1.1. (For Phase 2 Subjects Only) - Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study drug. If the urine test is positive, a serum pregnancy test will be required. - Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for at least 1 year. - Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study drug. - ECOG Performance Status ≤ 1. - Adequate organ function as defined in the protocol - Recovery to baseline or Grade ≤ 1 CTCAE v4 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy. - Patients must be able to provide informed consent and be willing to sign an approved consent form that conforms to federal and institutional guidelines Exclusion Criteria: - Previous treatment with and disease progression on a combination of a VEGF inhibitor and an immune checkpoint inhibitor. Patients who have been treated with and have progressed on a single agent VEGF inhibitor OR an immune checkpoint inhibitor will not be excluded. - Current use of immunosuppressive medication, EXCEPT for the following: - Topical, ocular, intra-articular, intranasal, and inhaled corticosteroids. - Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone equivalent. - Steroids as premedication for hypersensitivity reactions. - Active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent per treating physician's clinical judgment. Subjects with type 1 diabetes, vitiligo, psoriasis, hypothyroidism, or hyperthyroidism not requiring immunosuppressive medications are eligible. - Prior organ transplant including allogenic hematopoietic stem cell transplant. - Active infection requiring intravenous antibiotics (must be completed prior to registration). - Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment. - Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: - Cardiovascular disorders: - Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment. - Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias. - Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 6 months before first dose. - Any history of congenital long QT syndrome. - Presence of a non-healing wound. - Other clinically significant disorders that would preclude safe study participation including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis, psychiatric conditions with active suicidal ideation within the past year; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to apatinib or pembrolizumab. - History of severe hypersensitivity reaction to any monoclonal antibody. - Known history of testing positive for HIV or known acquired immunodeficiency syndrome. - Known history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or detectable HCV RNA if anti-HCV antibody screening test positive). - Live vaccine within 4 weeks of the first dose of pembrolizumab and while on trial is prohibited. - Packed red blood cell transfusions or erythropoietin therapy within 14 days prior to the study enrollment unless erythropoietin therapy has been used to maintain a stable condition for at least 1 month prior to the enrollment. - Palliative radiotherapy within 2 weeks of the first dose of study treatment. - Major surgery within 4 weeks of first dose of study medications. Minor procedures (e.g. port placement, endoscopy with intervention) within 2 weeks of first dose of study medications are allowed. - Chemotherapy, targeted small molecule therapy, or investigational therapy within 4 weeks of the first dose of study treatment. - Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4 Grade ≥ 3). - Subjects taking prohibited medications as described in the protocol with the exception of systemic corticosteroids as defined in the protocol. A washout period of at least 5 elimination half-lives (or as clinically indicated) should occur for prohibited medications prior to the start of treatment. ; PRIMARY OUTCOME: Incidence of dose limiting toxicities (DLTs) of Apatinib in combination with pembrolizumab; SECONDARY OUTCOME 1: Progression Free Survival (PFS)

No

TRIAL NAME: Phase II/III - Acne Scars; BRIEF: The purpose of this study is to evaluate the safety profile and the treatment effect of Isolagen TherapyTM and placebo when administered to facial acne scars. ; DRUG USED: laViv; DRUG CLASS: Biologic; INDICATION: Acne Scars ; TARGET: Fibroblasts; THERAPY: Monotherapy; LEAD SPONSOR: Castle Creek Biosciences, LLC.; CRITERIA: Inclusion Criteria: 1. Male or female, between 18 years and 65 years of age. 2. Investigator assessment of the acne scarring on each cheek of moderate to severe. 3. A history of acne scarring for more than 3 years. 4. Subject assesses the appearance of both sides of their facial acne scars as dissatisfied or very dissatisfied with appearance. Exclusion Criteria: 1. Significant active acne. 2. Use of oral antibiotic or retinoid active acne therapy within one year of enrollment. 3. Presence of hypertrophic scars on the cheeks. 4. More than 20% of treatment area comprised of ice pick scars or sinus tracts 5. Treatment area per cheek is less than 9 cm x cm 6. Unilateral or unbalanced acne scar distribution. 7. Physical attributes which prevent the assessment or treatment of the acne scars. 8. Treatment with an investigational product or procedure within 30 days prior to study enrollment or plans to participate in another clinical trial during the course of this study. 9. Previous treatment with Isolagen TherapyTM. 10. Use of Isotretinoin within one year of enrollment into study. 11. Use of permanent or semi-permanent dermal fillers in the treatment areas within defined time frames. 12. Disorders or drugs that increase bleeding or clotting. 13. Pregnant or lactating women or women trying to become pregnant during the study. 14. Excessive exposure to sun. 15. Smoking more than ½ pack of cigarettes per day. ; PRIMARY OUTCOME: Evaluator Live Acne Scarring Assessment Responders; SECONDARY OUTCOME 1: Evaluator Live Acne Scarring Assessment Responders

No

TRIAL NAME: Phase II - JS-OAP2-US01; BRIEF: This study is a double-blind, randomized, controlled study with two arms to evaluate JointStem as a treatment for subjects with osteoarthritis. Following a 2-week screening period, approximately 30 subjects will be randomly assigned into one of the following two arms in a 2:1 ratio (2 JointStem : 1 positive control). After each subject completes 6-month visit (Visit 6) and the data management team confirms all data have no issue, the individual database will be locked and the blinding will be open for the statistical analysis.Only subjects who are assigned will be requested to visit the study center for 9-month and 12-month follow-up visits (Visits 7 and 8). To see long-term effects of JointStem, all subjects who complete Visit 6 will be requested to visit the study center at 24-month after the injection. ; DRUG USED: JointStem; DRUG CLASS: Biologic; INDICATION: Osteoarthritis and Osteoarthritis Pain; TARGET: Stem Cells/Other Cell Therapies; THERAPY: Monotherapy; LEAD SPONSOR: Nature Cell Co. Ltd.; CRITERIA: Inclusion Criteria: - Subject who can give written informed consent - Male or female of any race, aged 22-60 - Subject who had osteoarthritis of knee diagnosed at least six months prior to Screening - Subject who has joint pain ≥ 40mm on VAS (Visual Analog Scale) at Screening - Subject who has swelling, tenderness and active range of motion ≥ Grade I at Screening - Subject who seeks invasive interventions of intra-articular injections - Subject who is willing to discontinue all pain medications for osteoarthritis except rescue medication (< acetaminophen 3.25 g per day) at least 72 hours prior to screening and throughout the duration of study - Subject who has radiographic evidence of grade 3 to 4 osteoarthritis based on the Kellgren and Lawrence radiographic criteria. - Female subject who is neither pregnant nor lactating - Subject who is able to comply with lifestyle guidelines, scheduled visits, treatment plan, laboratory tests, and other study procedures Exclusion Criteria: - Subject who has Body Mass Index (BMI) > 35 kg/m2 - Subject who has unstable knees - Subject who took any NSAID within two weeks from Screening - Subject who had any intra-articular injection therapy in any joint within 2 months from Screening - Subject who has any clinically significant disease, which is judged by the investigator to affect this clinical trial - Subject who has inflammatory arthropathy (rheumatoid, psoriatic, or avascular necrosis), and post traumatic or septic arthritis - Subject who has chondrocalcinosis, Paget's disease, Villonodular synovitis, and other non-OA joint diseases - Subject who has HIV/viral hepatitis - Subject who had knee surgery or radiation therapy in the affected joint within 6 months from Screening - Subject who had CVA attack within 6 months from Screening - Subject for whom the investigator judges the liposuction can cause any problem - Subject who has significant lab abnormalities - Subject who has history of local anesthetic allergy - Subject who took immunosuppressants such as Cyclosporin A or azathioprine within 6 weeks from Screening - (If a subject uses aspirin or plavix) Subject for whom it is determined that it would not be safe to stop the aspirin/plavix therapy for 2 weeks prior to Visit 2 - Subject who uses anticoagulants which cannot be stopped or corrected - Subject who had oral or intra-muscular corticosteroids within 30 days from Visit 2 - Subject who had intra-articular corticosteroid injection in any joint within 30 days from Visit 2 - Subject who had intra-articular hyaluronic acid injection within 30 days from Visit 2 - Subject who has known hypersensitivity (allergy) to hyaluronan (sodium hyaluronate) preparations or gram positive proteins - Subject who has knee joint infections or skin diseases or infections in the area of the injection site - Subject who has known systemic bleeding disorders - Subject who is an active drug/EtOH abuser - Subject who was enrolled in any other clinical trials within 2 months from Screening - Subject who the principal investigator considers inappropriate for the study due to any other reasons than those listed above - Subject whose MRI scan results at screening do not demonstrate any sign of cartilage damage ; PRIMARY OUTCOME: Change From Baseline on Western Ontario and McMaster Universities Arthritis Index (WOMAC) Score in JointStem Group; SECONDARY OUTCOME 1: Change From Baseline on WOMAC Between JointStem and Positive Control Groups

Yes

TRIAL NAME: Phase II/III - NAION; BRIEF: This study will determine the effect of QPI-1007 on visual function in subjects with recent-onset NAION and assess the safety and tolerability of intravitreal injections of QPI-1007 in this population. This study will also evaluate the structural changes in the retina following administration of QPI-1007. ; DRUG USED: QPI-1007; DRUG CLASS: New Molecular Entity (NME); INDICATION: Optic Neuritis (Ophthalmology); TARGET: Caspases; THERAPY: Monotherapy; LEAD SPONSOR: Quark Pharmaceuticals; CRITERIA: Key Inclusion Criteria: - Positive diagnosis of first episode of NAION in the study eye with symptom onset within 14 days prior to planned study drug administration/sham procedure - Best corrected visual acuity score in the study eye is better than or equal to 15 letter score, measured using the ETDRS visual acuity protocol at Day 1 prior to study drug administration/sham procedure. - Clear ocular media and able to undergo adequate pupil dilation to allow a good fundus examination Key Exclusion Criteria: - Present use or history of any treatment for the current episode of NAION, including systemic steroids, brimonidine, or traditional Chinese herbal medicine - Prior episode of NAION in the study eye only - Present use of drugs known to cause optic nerve or retinal toxicity at Day 1/Randomization, such as: chloroquine or hydroxychloroquine, ethambutol, Vigabatrin. Subjects who need to be prescribed any of these drugs during the course of the study will be discontinued from the trial. - Any medical condition, concomitant therapy, or previous incisional or laser surgery that, in the opinion of the Investigator, would preclude IVT injection in the study eye only - Clinical evidence of temporal arteritis ; PRIMARY OUTCOME: Effect of QPI-1007 as assessed by Best Corrected Visual Acuity (BCVA); SECONDARY OUTCOME 1: Mean change in BCVA score, as measured by ETDRS visual acuity protocol in the study eye

No

TRIAL NAME: Phase I - Single Dose; BRIEF: The aim of the current study was the pharmacokinetic and pharmacodynamic characterization of a single dose administration of four doses of FSH-GEX™ in healthy pituitary-suppressed female volunteers, in comparison with two marketed comparator products. ; DRUG USED: FSH-GEX; DRUG CLASS: Biologic; INDICATION: Reproductive Disorder; TARGET: Follicle-Stimulating Hormone Receptor (FSHR) ; THERAPY: Monotherapy; LEAD SPONSOR: Glycotope GmbH; CRITERIA: Inclusion Criteria: 1. Female subjects from 18-40 years of age. 2. Subjects must be in good health. 3. Subjects must be willing to use additional non-hormonal contraception 4. Subjects must have used a combined oral contraceptive (COC) for at least one cycle. 5. Vital signs which are within the following ranges at baseline measurements: systolic blood pressure of 90-140 mmHg, diastolic blood pressure of 50-90 mmHg and pulse rate of 40 - 100 bpm. 6. Subjects must have a body weight of minimally 50.0 kg with a BMI between 18.0 and 29.0 kg/m^2 at baseline measurements. 7. Able to provide written informed consent prior to study participation. 8. Able to communicate well with the investigator and to understand and comply with the requirements of the study. Exclusion Criteria: 1. Smokers of more than 10 cigarettes per day. 2. Average daily intake of more than 3 units of alcohol per day or an average weekly intake of more than 21 units alcohol. 3. Use of any prescription drug or ove the counter medication from screening until the end-of-study visit, without prior approval of the investigator. 4. Any drugs thay may reduce the effectiveness of COC from screening until the end-of-study visit. 5. Any follicle-stimulating hormone (FSH) preparation within 90 days prior to screening. 6. Administration of any investigational product or use of any investigational device within 30 days prior to screening. 7. Donation or loss of 500 mL or more blood within 90 days prior to first FSH-GEX™ dosing. 8. History of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated). 9. History of allergies for drugs, seafood, nuts, eggs, wasp-stings; history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to any of the study drugs. 10. Any surgical or medical condition which might alter the absorption, distribution, metabolism, or excretion of drugs or which may jeopardize the subject in case of participation in the study. 11. History or presence of any malignancy. 12. Determined or suspected pregnancy. 13. Breast feeding women. 14. History of (or current) endocrine abnormalities. 15. Contraindication for the use of oral contraceptives. 16. Contraindication for the use of follitropin alfa, FSH or any of the excipients (hypersensitivity to follitropin alfa, FSH or any of the excipients; tumors of the hypothalamus or the pituitary gland; ovarian enlargement or cyst not due to polycystic ovarian disease; gynecological bleeding of unknown origin; ovarian, uterine, or mammary carcinoma). 17. Porphyria or family history of porphyria. 18. History of ovarian surgery. 19. Any ovarian or abdominal abnormality that would interfere with adequate ultrasound investigation. 20. An abnormal cervical smear. 21. History or presence of an immune-compromising disease, or a positive human immunodeficiency virus (HIV) test result in the past or at the screening visit. 22. History of Hepatitis B or C, or a positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result at the screening visit. 23. History of drug or alcohol abuse within the 12 months prior to the screening visit or evidence of such abuse. 24. Planned surgery or hospitalization during the period of the study. 25. Concurrent participation or participation within 30 days before screening in another clinical trial, or participation in more than 3 clinical studies within 12 months, prior to the expected date of enrolment into the study. 26. Injection of one or more doses of any depot contraceptive drug /drug combination or hormonal implants <= 10 months prior to screening. ; PRIMARY OUTCOME: to assess the safety and (local) tolerability of FSH-GEX™ following single rising dose administration by subcutaneous injection; SECONDARY OUTCOME 1: to assess the pharmacodynamic effect of FSH-GEX™ following single rising dose administration by subcutaneous injection (part 1)

Yes

TRIAL NAME: Phase III - CALIMA (w/ High-Dose ICS-LABA) (52 weeks); BRIEF: The purpose of this study is to determine whether Benralizumab reduces the exacerbation rate in patients with a history of asthma exacerbations and uncontrolled asthma receiving ICS-LABA with or without oral corticosteroids and additional asthma controllers. ; DRUG USED: Fasenra; DRUG CLASS: Biologic; INDICATION: Asthma; TARGET: IL-5 (Interleukin-5) and IL-5 Receptor (IL-5R); THERAPY: Combination; LEAD SPONSOR: AstraZeneca; CRITERIA: Inclusion Criteria: 1. Provision of informed consent prior to any study specific procedures 2. Female and male aged 12 to 75 years, inclusively, at the time of Visit 1 3. History of physician-diagnosed asthma requiring treatment with medium-to-high dose ICS (>250µg fluticasone dry powder formulation equivalents total daily dose) and a LABA, for at least 12 months prior to Visit 1. 4. Documented treatment with ICS and LABA for at least 3 months prior to Visit 1 with or without oral corticosteroids and additional asthma controllers. The ICS and LABA can be parts of a combination product or given by separate inhalers. The ICS dose must be greater than or equal to 500 μg/day fluticasone propionate dry powder formulation or equivalent daily. For ICS/LABA combination preparations, the mid-strength approved maintenance dose in the local country will meet this ICS criterion. Exclusion criteria: 1. Clinically important pulmonary disease other than asthma (e.g. active lung infection, COPD, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts (e.g. allergic bronchopulmonary aspergillosis/mycosis, Churg- Strauss syndrome, hypereosinophilic syndrome) 2. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could: - Affect the safety of the patient throughout the study - Influence the findings of the studies or their interpretations - Impede the patient's ability to complete the entire duration of study 3. Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained or during the screening/run-in period 4. Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in period, which in the opinion of the Investigator, may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or the patient's ability to complete entire duration of the study ; PRIMARY OUTCOME: Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils >=300/uL; SECONDARY OUTCOME 1: Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils <300/uL

Yes

TRIAL NAME: Phase III - OMTT; BRIEF: The purpose of this study is to evaluate EXE844 plus tympanostomy tubes compared to tympanostomy tubes only based on sustained clinical cure at end-of-therapy (EOT). ; DRUG USED: Xtoro; DRUG CLASS: New Molecular Entity (NME); INDICATION: Ear Infections (Antibacterial); TARGET: Gram-Negative Bacteria, Topoisomerase II (DNA gyrase) and IV; THERAPY: Monotherapy and Combo Therapy; LEAD SPONSOR: Alcon Research; CRITERIA: Inclusion Criteria: - Recurrent acute otitis media (RAOM) or chronic otitis media with effusion (COME) and eligible for bilateral myringotomy and tympanostomy tube insertion. - Suspected bacterial infection at time of surgery in at least 1 ear. - Willing to refrain from water immersion of the ears following surgery without the use of adequate ear protection during swimming, bathing, showering and other water-related activities. - Legally Authorized Representative (LAR) must read and sign the informed consent. - Parent or caregiver must agree to comply with the requirements of the study and administer study medication as directed, complete required study visits, and comply with the protocol. - Other protocol-specified inclusion criteria may apply. Exclusion Criteria: - Previous otologic or otologic-related surgery within the past 30 days or ongoing complications. - Middle ear pathology in either ear other than otitis media. - Current acute otitis externa (AOE), malignant otitis externa (MOE) or other conditions which could interfere with evaluation of the study drug. - Any systemic disease or disorder, complicating factor or structural abnormality that would negatively affect the conduct or outcome of the study based upon assessment by the Investigator. - Known or suspected allergy or hypersensitivity to quinolones or other active or inactive ingredients present in the medications to be used in the study. - Other protocol-specified exclusion criteria may apply. ; PRIMARY OUTCOME: Percentage of Subjects With Sustained Clinical Cure at Day 8; SECONDARY OUTCOME 1: Percentage of Subjects With Microbiological Success at Day 14

Yes

TRIAL NAME: Phase IIb - NAV3-32; BRIEF: This study is a comparison of quantitative Tc 99m tilmanocept imaging with IHC analysis of CD206 expression in synovial tissue of RA subjects. ; DRUG USED: Tc 99m Tilmanocept Planar Imaging; DRUG CLASS: New Molecular Entity (NME); INDICATION: Rheumatoid Arthritis - Imaging; TARGET: Macrophages, Mannose, Radiopharmaceutical; THERAPY: Monotherapy; LEAD SPONSOR: Navidea Biopharmaceuticals; CRITERIA: Inclusion Criteria: 1. The subject has provided written informed consent with HIPAA (Health Information Portability and Accountability Act) or equivalent authorization before the initiation of any study-related procedures. 2. Women and men of childbearing potential must use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) for the duration of the study. 3. The subject is at least 18 years of age and was ≥ 18 years of age at the time of RA diagnosis. 4. The subject has RA as determined by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Classification Criteria (score of ≥ 6/10 at or before screening). 5. The subject has a 28-joint disease activity score (DAS28) of ≥ 3.2 (includes the C-reactive protein [CRP] test and visual analog scale [VAS]). 6. Subjects receiving traditional DMARDs must have been on therapy for ≥ 90 days and at a stable dose for ≥ 30 days prior to the first imaging visit (Day 0). 7. If the subject is receiving biologic disease-modifying antirheumatic drug (bDMARD) or janus kinase (JAK) inhibitor therapy, they have been at a stable dose > 180 days prior to the first imaging visit (Day 0). 8. If the subject is receiving NSAIDs (nonsteroidal anti-inflammatory drug) or oral corticosteroids, the dose has been at a stable dose for ≥ 28 days prior to imaging. The corticosteroid dose should be ≤ 10 mg/day of prednisone or an equivalent steroid dose. 9. The subject has a hand or wrist joint with a minimum ultrasound gray-scale synovitis score of 2 (range 0 to 3). Exclusion Criteria: 1. The subject is pregnant or lactating. 2. The subject size or weight is not compatible with imaging per the investigator. 3. The subject has had or is currently receiving radiation therapy or chemotherapy. 4. The subject has renal insufficiency as demonstrated by a glomerular filtration rate of < 60 mL/min. 5. The subject has hepatic insufficiency as demonstrated by ALT (alanine aminotransferase [SGPT]) or AST (aspartate aminotransferase [SGOT]) greater than 3 times the upper limit of normal. 6. The subject has any severe, acute, or chronic medical conditions and/or psychiatric conditions and/or laboratory abnormalities that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration that would deem the subject inappropriate for study participation. 7. The subject has a known allergy to or has had an adverse reaction to dextran exposure. 8. The subject has received an investigational product within 30 days prior to the Tc 99m tilmanocept administration (Day 0). 9. The subject has received intra-articular corticosteroids ≤ 8 weeks prior to imaging (Day 0). 10. The subject has received any radiopharmaceutical within 7 days or 10 half-lives prior to the administration of Tc 99m tilmanocept (Day 0). 11. The subject has an intolerance to anesthetic and antiseptic agents indicated for the synovial biopsy procedure. 12. The subject is currently receiving anticoagulants (oral anti-platelet agents are permitted) or has a condition that is contraindicated with ultrasound-guided synovial biopsy e.g., needle phobia. ; PRIMARY OUTCOME: Correlation between joint-specific tilmanocept uptake and CD206 expression; SECONDARY OUTCOME 1: Correlation between joint-specific tilmanocept uptake and CD68 and CD163 expression

No

TRIAL NAME: Phase III - VITAL (Brigham and Women's Hospital); BRIEF: The VITamin D and OmegA-3 TriaL (VITAL) is a randomized clinical trial in 25,871 U.S. men and women investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk of developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. The 5-year intervention phase (study pill-taking, median 5.3 years) has ended; post-intervention observational follow-up of study participants is ongoing. ; DRUG USED: Lovaza; DRUG CLASS: New Molecular Entity (NME); INDICATION: Dyslipidemia / Hypercholesterolemia; TARGET: Diglycerol Acyltransferase (DGAT), Lipoprotein lipase, PPAR gamma; THERAPY: Combination; LEAD SPONSOR: Brigham and Women's Hospital; CRITERIA: To be eligible for the study, respondents had to, at study entry,: 1. be men aged 50 or older or women aged 55 or older; 2. have no history of cancer (except non-melanoma skin cancer), heart attack, stroke, transient ischemic attack, angina pectoris, coronary-artery bypass grafting, or percutaneous coronary intervention; 3. have none of the following safety exclusions: history of renal failure or dialysis, hypercalcemia, hypo- or hyperparathyroidism, severe liver disease (cirrhosis), or sarcoidosis or other granulomatous diseases such as active chronic tuberculosis or granulomatosis with polyangiitis (Wegener's); 4. have no allergy to fish or soy; 5. have no other serious illness that would preclude participation; 6. be consuming no more than 800 IU of vitamin D from all supplemental sources combined (individual vitamin D supplements, calcium+vitamin D supplements, medications with vitamin D [e.g., Fosamax Plus D], and multivitamins), or, if taking, willing to decrease or forego such use during the trial; 7. be consuming no more than 1200 mg/d of calcium from all supplemental sources combined, or, if taking, willing to decrease or forego such use during the trial; 8. not be taking fish oil supplements, or, if taking, willing to forego their use during the trial ; PRIMARY OUTCOME: Number of Participants With Invasive Cancer of Any Type; SECONDARY OUTCOME 1: Number of Participants Who Died From Invasive Cancer of Any Type

No

TRIAL NAME: Phase II - vs. Axitinib; BRIEF: The purpose of this study was to evaluate the progression free survival (PFS), based on investigator radiologic review, of AGS-16C3F compared to axitinib in subjects with metastatic renal cell carcinoma. ; DRUG USED: AGS-16C3F; DRUG CLASS: Biologic; INDICATION: Renal Cell Cancer (RCC); TARGET: Antibody-drug Conjugate (ADC), Ectonucleotide Pyrophosphatase/Phosphodiesterase 3 (ENPP3); THERAPY: Monotherapy; LEAD SPONSOR: Astellas Pharma Global Development, Inc.; CRITERIA: Inclusion Criteria: - Histologically confirmed diagnosis of RCC - Non-clear subjects must be ENPP3 positive, defined as IHC H-score ≥15 - Has evidence of progression on or after the last regimen received: - Clear cell subject: must have received at least 2 prior systemic regimens, one of which is an anti-VEGF agent. - Non-clear cell subject: must have received at least one prior anti-VEGF regimen - Has measurable disease according to Response Criteria for Solid Tumors (RECIST v.1.1) - Has Eastern Cooperative Group (ECOG) performance status of 0 or 1 - Has archive tumor tissue from primary tumor or metastatic site (excluding bone), for which the source and availability have been confirmed. - If no archive tissue is available, the subject may elect to have a biopsy performed to obtain tissue. - Has adequate organ function including: - Hematopoietic function as follows: 1. Absolute neutrophil count (ANC) ≥ 1.5 x 10 9/L 2. Platelet count ≥ 100 x 10 9/L 3. Hemoglobin ≥ 9 g/dL (transfusions are allowed) - Renal Function as follows: 1. Creatinine ≤ 1.5 x upper limit of normal (ULN), or calculated glomerular filtration rate (GFR) > 40 mL/min (Cockcroft-Gault) if creatinine > 1.5x ULN - Hepatic function, as follows: 1. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN or ≤ 5x ULN if known liver metastases 2. Total bilirubin ≤ 1.5 x ULN - Prothrombin time (PT) and activated partial thromboplastin time (aPTT) levels ≤1.5 x ULN. If institution does not report PT value, the international normalization ratio (INR) must be ≤ ULN. - If subject is receiving Coumadin (warfarin), a stable international normalization ratio (INR) of 2-3 is required. - No clinical symptoms of hypothyroidism - Urine Protein to Creatinine Ratio (uPCR) < 2.0 - If uPCR ≥ 2.0 then a 24-hour urine collection can be performed to qualify. If this is performed to qualify, the protein result must be < 2 g per 24 hours. - Female subject must either: - Be of non-childbearing potential: 1. post-menopausal (defined as at least 1 year without any menses) prior to Screening, or 2. documented surgically sterile - Or, if of childbearing potential, 1. Agree not to try to become pregnant during the study and for 6 months after the final study drug administration 2. And have a negative serum pregnancy test ≤ 10 days of cycle 1, day 1 (C1D1) - And, if heterosexually active, agree to consistently use 2 forms of highly effective birth control* (at least one of which must be a barrier method) starting at Screening and throughout the study period and for 6 months after the final study drug administration. - Female subject must agree not to breastfeed starting at Screening and throughout the study period, and for 6 months after the final study drug administration. - Female subject must not donate ova starting at Screening and throughout the study period, and for 6 months after the final study drug administration. - Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception* consisting of 2 forms of birth control (at least one of which must be a barrier method) starting at Screening and continue throughout the study period, and for 6 months after the final study drug administration - Male subject must not donate sperm starting at Screening and throughout the study period and, for 6 months after the final study drug administration Note: *Highly effective forms of birth control include: - Consistent and correct usage of established oral contraception. - Established intrauterine device (IUD) or intrauterine system (IUS). - Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository Exclusion Criteria: - Has previously been treated with axitinib, AGS-16C3F, or AGS-16M8F - Has untreated brain metastasis. In the case of a solitary brain metastasis which has been resected, there must be evidence of a disease-free interval of at least 3 months post-surgery. For brain metastases treated with whole brain or stereotactic radiation therapy, brain imaging must be stable > 3 months. All subjects previously treated for brain metastases must be stable off corticosteroid therapy for at least 28 days prior to C1D1. - Has uncontrolled hypertension defined as blood pressure > 150/90 on medication(s) by 2 blood pressure readings taken at least 1 hour apart. - Has gastrointestinal abnormalities including: - inability to take oral medication; - requirement for intravenous alimentation; - prior surgical procedures affecting absorption including total gastric resection; - active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy; - malabsorption syndromes such as celiac disease, cystic fibrosis, inflammatory bowel disease, systemic sclerosis, and carcinoid syndrome - Has ocular conditions such as: - Active infection or corneal ulcer - Monocularity - Visual acuity of 20/70 or worse in both eyes - History of corneal transplantation - Contact lens dependent (if using contact lens, must be able to switch to glasses during the entire study duration) - Uncontrolled glaucoma (topical medications allowed) - Uncontrolled or active ocular problems (e.g., retinopathy, macular edema, active uveitis, wet macular degeneration) requiring surgery, laser treatment, or intravitreal injections - Papilledema or other active optic nerve disorder - Has used any investigational drug (including marketed drugs not approved for this indication) ≤ 14 days of C1D1. No time limit applies to the use of marketed drugs approved for this indication provided that the subject has progressed on the treatment and all toxicities attributable to the drug have resolved, returned to baseline or stabilized. - Has known sensitivity to any of the ingredients of: - investigational product AGS-16C3F and/or, - Inlyta® (axitinib) and/or, - 1% prednisolone acetate ophthalmic suspension and any other corticosteroids. - Is currently using (i.e., within 14-days prior to first dose) drugs that are known strong CYP3A4/5 inhibitors / inducers. - Thromboembolic event (e.g., deep vein thrombosis [DVT] and pulmonary embolism [PE]) ≤ 4 weeks of C1D1. - Subjects who had a thromboembolic event ≤ 4 weeks of C1D1 must be receiving adequate anticoagulation treatment for at least 2 weeks before C1D1 and must continue as clinically indicated post first dose - Has history bleeding disorders (e.g., pulmonary hemorrhage, significant hemoptysis, menometrorrhagia not responding to hormonal treatment) ≤ 2 months before C1D1 - Has active angina or Class III or IV Congestive Heart Failure (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 6 months of randomization, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, congestive heart failure, or arrhythmias not controlled by medication. - Had major surgery ≤ 4 weeks of C1D1 - Is pregnant (confirmed by positive serum pregnancy test) or lactating - Has active infection requiring treatment with systemic (intravenous or oral) anti-infectives (antibiotic, antifungal, or antiviral agent) ≤ 10 days of C1D1 - Is unwilling or unable to comply with study requirements - Has any medical or psychiatric disorder that compromises the ability of the subject to give written informed consent, and/or comply with the study procedures. ; PRIMARY OUTCOME: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigator Radiologic Review; SECONDARY OUTCOME 1: PFS Per RECIST v1.1 as Assessed by Blinded Central Radiology Assessment

No

TRIAL NAME: Phase II - w/MTX Therapy; BRIEF: The purpose of this study is to assess the efficacy and safety of CNTO6785 in participants with active rheumatoid arthritis (RA) despite methotrexate (MTX) therapy. ; DRUG USED: FTC001; DRUG CLASS: Biologic; INDICATION: Rheumatoid Arthritis (RA); TARGET: IL-17 (Interleukin 17); THERAPY: Monotherapy; LEAD SPONSOR: Janssen Research & Development, LLC; CRITERIA: Inclusion Criteria: - Have a diagnosis of rheumatoid arthritis (RA) (according to the revised 1987 criteria of the American Rheumatism Association) and have had RA for at least 6 months prior to the date of signing the informed consent at screening - Have active RA defined study as persistent disease activity with both of the following criteria: at least 6 swollen and 6 tender joints using a 66/68 joint count at the time of screening and at baseline; and serum C-reactive protein (CRP) ≥ 0.8 mg/dL at screening or erythrocyte sedimentation rate (ESR) ≥ 28 mm in the first hour at screening or baseline - Have been treated with and tolerated methotrexate (MTX) treatment at dosages from 7.5 to 25 mg/week, inclusive, for a minimum of 6 months prior to screening and must have a stable MTX dose for a minimum of 6 weeks prior to the first dosing with study agent Exclusion Criteria: - Has inflammatory diseases other than RA, that might confound the evaluation of the benefit of study agent therapy - Has a diagnosis of fibromyalgia - Has a recent history (within 12 months prior to screening) of uncontrolled, chronic disease including, but not limited to, pulmonary, psychiatric, and metabolic disturbances, cardiovascular, endocrine, neurological, hepatic, gastrointestinal, renal, hematological, or urological diseases that the investigator believes are clinically significant - At screening, the results of laboratory tests must meet protocol-specified criteria - Has ever received any approved or investigational biologic agent for a rheumatic indication ; PRIMARY OUTCOME: The proportion of participants who achieve an ACR 20 response at Week 16; SECONDARY OUTCOME 1: Change from baseline in DAS28 (CRP) at Week 16

No

TRIAL NAME: Phase I - NIAID; BRIEF: This is a phase I, open-label, dose-ranging clinical trial in males and non-pregnant females, starting at 18 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of mRNA-1273 manufactured by ModernaTX, Inc. mRNA-1273 is a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine that encodes for a full-length, prefusion stabilized spike (S) protein of SARS-CoV-2. Enrollment will occur at up to 3 domestic clinical research sites. Up to one hundred and fifty-five subjects will be enrolled into one of thirteen cohorts (10 micrograms [mcg], 25 mcg, 50 mcg, 100 mcg, and 250 mcg). Subjects will receive an intramuscular (IM) injection (0.5 milliliters [mL]) of mRNA-1273 on Days 1 and 29 in the deltoid muscle and will be followed through 12 months post second vaccination (Day 394). Follow-up visits will occur 1, 2, and 4 weeks post each vaccination (Days 8, 15, 29, 36, 43, and 57), as well as 3, 6, and 12 months post second vaccination (Days 119, 209, and 394). The primary objective is to evaluate the safety and reactogenicity of a 2-dose vaccination schedule of mRNA-1273, given 28 days apart, across 5 dosages in healthy adults. Optional Substudy: This is an optional third mRNA-1273 vaccination substudy, in subjects 18 years of age and older, who received both the first and second mRNA-1273 vaccinations in the main study and meet all other substudy eligibility criteria. This optional third mRNA-1273 vaccination substudy is designed to assess safety, reactogenicity, and immunogenicity through 12 months post third vaccination (Day 731). Subjects who receive the third mRNA-1273 vaccination will exit the Schedule of Activities for the main study and will enter the Schedule of Activities for the optional substudy. Up to one hundred and twenty subject will be enrolled into two cohorts (consisting of participating subjects who received 2 doses of 25 or 50 mcg and participating subjects who received 2 doses of 100 and 250 mcg). Subjects will receive an IM injection (0.5 mL) at a dosage of 100 mcg/0.5 mL. The primary objective is to evaluate the safety and reactogenicity of a third mRNA-1273 vaccination, at a dosage of 100 mcg. ; DRUG USED: mRNA-1273; DRUG CLASS: Vaccine; INDICATION: COVID-19 Prevention; TARGET: Immune System, SARS-CoV-2; THERAPY: Monotherapy; LEAD SPONSOR: National Institute of Allergy and Infectious Diseases (NIAID); CRITERIA: Inclusion Criteria: A subject must meet all of the following criteria to be eligible to participate in this study: 1. Provides written informed consent prior to initiation of any study procedures. 2. Be able to understand and agrees to comply with planned study procedures and be available for all study visits. 3. Agrees to the collection of venous blood per protocol. 4. Male or non-pregnant female, >/= to 18 years of age at time of enrollment. 5. Body Mass Index (BMI) 18.0-35.0 kg/m^2, inclusive (< 56 years of age), at screening; BMI 18.0-30.0 kg/m^2, inclusive (>/= 56 years of age), at screening. 6. Women of childbearing potential* must agree to use or have practiced true abstinence** or use at least one acceptable primary form of contraception.***, **** Note: These criteria are applicable to females in a heterosexual relationship and child-bearing potential (i.e., the criteria do not apply to subjects in a same sex relationship). - Not of childbearing potential - post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, tubal ligation/salpingectomy, or Essure(R) placement). - True abstinence is 100% of time no sexual intercourse (male's penis enters the female's vagina). (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception). - Acceptable forms of primary contraception include monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more prior to the subject's first vaccination, intrauterine devices, birth control pills, and injectable/implantable/insertable hormonal birth control products. - Must use at least one acceptable primary form of contraception for at least 30 days prior to the first vaccination and at least one acceptable primary form of contraception for 60 days after the last vaccination. 7. Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to each vaccination. 8. Male subjects of childbearing potential*: use of condoms to ensure effective contraception with a female partner of childbearing potential from first vaccination until 60 days after the last vaccination. *Biological males who are post-pubertal and considered fertile until permanently sterile by bilateral orchiectomy or vasectomy. 9. Male subjects agree to refrain from sperm donation from the time of first vaccination until 60 days after the last vaccination. 10. In good health.* *As determined by medical history and physical examination to evaluate acute or ongoing chronic medical diagnoses/conditions that have been present for at least 90 days, which would affect the assessment of safety of subjects. Chronic medical diagnoses/conditions should be stable for the last 60 days (no hospitalizations, emergency room (ER), or urgent care for condition or need for supplemental oxygen). This includes no change in chronic prescription medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis/condition in the 60 days before enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or done for financial reasons, and in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the participating site principal investigator (PI) or appropriate sub-investigator, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the participating site PI or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity, and do not indicate a worsening of medical diagnosis/condition. Similarly, medication changes subsequent to enrollment and study vaccination are acceptable provided the change was not precipitated by deterioration in the chronic medical condition, and there is no anticipated additional risk to the subject or interference with the evaluation of responses to study vaccination. 11. Oral temperature is less than 100.0 degrees Fahrenheit (37.8 degrees Celsius). 12. Pulse no greater than 100 beats per minute. 13. Systolic blood pressure (BP) is 85 to 150 mm Hg, inclusive. 14. Clinical screening laboratory evaluations (white blood cell (WBC), hemoglobin (Hgb), platelets (PLTs), alanine transaminase (ALT), aspartate transaminase (AST), creatinine (Cr), alkaline phosphatase (ALP), total bilirubin (T. Bili), Lipase, prothrombin time (PT), and partial thromboplastin time (PTT)) are within acceptable normal reference ranges at the clinical laboratory being used. 15. Must agree to have samples stored for secondary research. 16. Agrees to adhere to Lifestyle Considerations throughout study duration. 17. Must agree to refrain from donating blood or plasma during the study (outside of this study). Leukapheresis Inclusion Criteria: A subject must meet all of the following criteria to be eligible for leukapheresis: 1. Written informed consent for leukapheresis is provided. 2. Weight >/= 110 pounds. 3. Screening laboratory evaluations are within acceptable ranges at the site where the leukapheresis procedure will be performed. 4. Negative urine or serum pregnancy test within 48 hours of the leukapheresis procedure for women of childbearing potential. 5. Adequate bilateral antecubital venous access. 6. No use of blood thinners, aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) at least 5 days before the leukapheresis procedure. 7. Enrolled in cohorts 2, 3, 5, 10, or 11, and possibly cohort 6, if enrolled, and completed the two-dose vaccination series. Optional Substudy Inclusion Criteria: 1. Enrolled in the main study and received both the first and second mRNA-1273 vaccinations. 2. Provides written informed consent for the third mRNA-1273 vaccination. 3. Agrees to the collection of venous blood per substudy. 4. Must agree to have samples stored for secondary research. 5. Women of childbearing potential have had a negative urine pregnancy test within 24 hours before the third mRNA-1273 vaccination. 6. Women of childbearing potential* must agree to use or have practiced true abstinence** or use at least one acceptable primary form of contraception.***/**** - Not of childbearing potential - post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, tubal ligation/salpingectomy, or Essure® placement). - True abstinence is 100% of time no sexual intercourse (male's penis enters the female's vagina). (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception). - Acceptable forms of primary contraception include monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more prior to the subject's first vaccination, intrauterine devices, birth control pills, and injectable/implantable/insertable hormonal birth control products. ****Must use at least one acceptable primary form of contraception for at least 30 days prior to the third mRNA-1273 vaccination and for at least 30 days after the third mRNA-1273 vaccination. Exclusion Criteria: A subject who meets any of the following criteria will be excluded from participation in this study: 1. Positive pregnancy test either at screening or just prior to each vaccine administration. 2. Female subject who is breastfeeding or plans to breastfeed from the time of the first vaccination through 60 days after the last vaccination. 3. Has any medical disease or condition that, in the opinion of the participating site principal investigator (PI) or appropriate sub-investigator, precludes study participation.* *Including acute, subacute, intermittent or chronic medical disease or condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial. 4. Presence of self-reported or medically documented significant medical or psychiatric condition(s).* *Significant medical or psychiatric conditions include but are not limited to: Respiratory disease (e.g., chronic obstructive pulmonary disease [COPD], asthma) requiring daily medications currently or any treatment of respiratory disease exacerbations (e.g., asthma exacerbation) in the last 5 years. Asthma medications: inhaled, oral, or intravenous (IV) corticosteroids, leukotriene modifiers, long and short acting beta agonists, theophylline, ipratropium, biologics. Significant cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease), history of myocarditis or pericarditis as an adult, myocardial infarction (MI) within past 6 months, coronary artery bypass surgery or stent placement, or uncontrolled cardiac arrhythmia. Neurological or neurodevelopmental conditions (e.g., history of migraines in the past 5 years, epilepsy, stroke, seizures in the last 3 years, encephalopathy, focal neurologic deficits, Guillain-Barré syndrome, encephalomyelitis, transverse myelitis, stroke or transient ischemic attack, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, or Alzheimer's disease). Ongoing malignancy or recent diagnosis of malignancy in the last five years excluding basal cell and squamous cell carcinoma of the skin, which are allowed. An autoimmune disease, including hypothyroidism without a defined non-autoimmune cause, localized or history of psoriasis. An immunodeficiency of any cause. Chronic kidney disease, estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m^2. 5. Has an acute illness*, as determined by the participating site PI or appropriate sub-investigator, with or without fever [oral temperature >/= 38.0 degrees Celsius (100.4 degrees Fahrenheit)] within 72 hours prior to each vaccination. *An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the participating site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol. 6. Has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) types 1 or 2 antibodies at screening. 7. Has participated in another investigational study involving any investigational product* within 60 days, or 5 half-lives, whichever is longer, before the first vaccine administration. *study drug, biologic or device 8. Currently enrolled in or plans to participate in another clinical trial with an investigational agent* that will be received during the study-reporting period.** *Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication. **13 months after the first vaccination. 9. Has previously participated in an investigational study involving lipid nanoparticles (LNPs) (a component of the investigational vaccine assessed in this trial). 10. Has a history of hypersensitivity or severe allergic reaction (e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction) to any previous licensed or unlicensed vaccines. 11. Chronic use (more than 14 continuous days) of any medications that may be associated with impaired immune responsiveness.* *Including, but not limited to, systemic corticosteroids exceeding 10 mg/day of prednisone equivalent, allergy injections, immunoglobulin, interferon, immunomodulators, cytotoxic drugs, or other similar or toxic drugs during the preceding 6-month period prior to vaccine administration (Day 1). The use of low dose topical, ophthalmic, inhaled and intranasal steroid preparations will be permitted. 12. Anticipating the need for immunosuppressive treatment within the next 6 months. 13. Received immunoglobulins and/or any blood or blood products within the 4 months before the first vaccine administration or at any time during the study. 14. Has any blood dyscrasias or significant disorder of coagulation. 15. Has any chronic liver disease, including fatty liver. 16. Has a history of alcohol abuse or other recreational drug (excluding cannabis) use within 6 months before the first vaccine administration. 17. Has a positive test result for drugs of abuse at screening or before the first vaccine administration. If cannabis is the only detected drug, inclusion is permitted. 18. Has any abnormality or permanent body art (e.g., tattoo) that would interfere with the ability to observe local reactions at the injection site (deltoid region). 19. Received or plans to receive a licensed, live vaccine within 4 weeks before or after each vaccination. 20. Received or plans to receive a licensed, inactivated vaccine within 2 weeks before or after each vaccination. 21. Receipt of any other SARS-CoV-2 or other experimental coronavirus vaccine at any time prior to or during the study. 22. Close contact of anyone known to have SARS-CoV-2 infection within 30 days prior to vaccine administration. 23. History of COVID-19 diagnosis. 24. On current treatment with investigational agents for prophylaxis of COVID-19. 25. Current use of any prescription or over-the-counter medications within 7 days prior to vaccination, unless approved by the investigator or necessary to manage a chronic condition. 26. Plan to travel outside the United States (US) (continental US, Hawaii, and Alaska) from enrollment through 28 days after the last vaccination. 27. Reside in a nursing home or other skilled nursing facility or have a requirement for skilled nursing care. 28. Non-ambulatory. 29. For subjects >/= 56 years of age, history of chronic smoking within the prior year. 30. For subjects >/= 56 years of age, current smoking or vaping. 31. For subjects >/= 56 years of age, individuals currently working with high risk of exposure to SARS-CoV-2 (e.g., active health care workers with direct patient contact, emergency response personnel). Optional Substudy Exclusion Criteria: 1. Anaphylaxis or other systemic hypersensitivity reaction following a mRNA-1273 or any other vaccination. 2. Immediate allergic reaction of any severity after mRNA-1273 or any of its components.* *Including polyethylene glycol (PEG) 3. Immediate allergic reaction of any severity to polysorbate.* *Due to potential cross-reactive hypersensitivity with the vaccine ingredient PEG 4. History of an SAE judged related to mRNA-1273 vaccine. 5. Female subject who is breastfeeding or plans to breastfeed from the time of the third mRNA-1273 vaccination through 30 days after the third mRNA-1273 vaccination. 6. Has an acute illness*, as determined by the participating site PI or appropriate sub-investigator, with or without fever [oral temperature >/=38.0°C (100.4°F)], within 72 hours prior to the third mRNA-1273 vaccination. *An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the participating site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the substudy. 7. Has received any approved, authorized or investigational COVID-19 vaccine outside of this trial. 8. Any clinically significant medical condition that, in the opinion of the investigator, poses an additional risk to the subject from vaccination. 9. History of documented COVID-19 infection. 10. Has any medical disease or condition that, in the opinion of the participating site PI or appropriate sub-investigator, precludes substudy participation. 11. Received or plans to receive a licensed vaccine, other than a COVID-19 vaccine, within 2 weeks before or after the third mRNA-1273 vaccination. ; PRIMARY OUTCOME: Frequency of Any Medically-attended Adverse Events (MAAEs); SECONDARY OUTCOME 1: Geometric Mean Fold Rise (GMFR) in IgG Titer From Baseline Against RBD

Yes

TRIAL NAME: Phase III - ADJUNCT TWO; BRIEF: This trial is conducted in Africa, Europe and North America. The purpose of the trial is to investigate the efficacy and safety of liraglutide adjunct to insulin treatment in type 1 diabetes. ; DRUG USED: Victoza; DRUG CLASS: New Molecular Entity (NME); INDICATION: Diabetes Mellitus, Type I; TARGET: GLP-1 Receptor; THERAPY: Combination; LEAD SPONSOR: Novo Nordisk A/S; CRITERIA: Inclusion Criteria: - Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial - Male or female, aged equal to or greater than 18 years at the time of signing informed consent - Type 1 diabetes mellitus (as diagnosed clinically) 12 months or longer prior to Visit 1 (i.e. screening) - Treatment with basal bolus or CSII (continuous subcutaneous insulin infusion, insulin pump) treatment 6 months or longer prior to Visit 1 (i.e. screening) - Stable insulin treatment 3 months or longer prior to Visit 1 (i.e. screening), as judged and documented by the investigator - HbA1c 7.0-10.0 percent (Diabetes Control and Complications Trial (DCCT)), both inclusive, by central laboratory analysis (Visit 1, screening) corresponding to 53-86 mmol/mol (International Federation of Clinical Chemistry (IFCC)) Exclusion Criteria: - Prior use of glucagon-like peptide-1 (GLP-1) receptor agonist or dipeptidyl peptidase IV (DPPIV) inhibitors - Use of any medication, which in the investigator's opinion could interfere with the glycaemic control (e.g. systemic corticosteroids, pramlintide (Symlin®)) or affect the subject's safety. Premix insulin is not allowed - Known proliferative retinopathy or maculopathy requiring acute treatment - Severe neuropathy, in particular autonomic neuropathy, i.e. gastroparesis, as judged by the investigator - Uncontrolled/untreated blood pressure at screening (Visit 1) (after resting for 5 minutes) while sitting greater than 160 mmHg for systolic or greater than 100 mmHg for diastolic (repeated measurement at Visit 2 (prior to performing the trial related activities) is allowed to exclude white-coat hypertension) - History of acute or chronic pancreatitis - Screening (Visit 1) calcitonin value equal to or greater than 50 ng/L ; PRIMARY OUTCOME: Change From Baseline in Glycosylated Haemoglobin (HbA1c); SECONDARY OUTCOME 1: Change From Baseline in Body Weight

No

TRIAL NAME: Phase III - US; BRIEF: A comparison of the efficacy of APD421 and placebo in the prevention of PONV in patients at moderate-to-high risk of PONV. ; DRUG USED: Barhemsys; DRUG CLASS: Non-NME; INDICATION: Emesis; TARGET: Dopamine 2 (D2) Receptor, Dopamine 3 (D3) Receptor; THERAPY: Monotherapy; LEAD SPONSOR: Acacia Pharma Ltd; CRITERIA: Inclusion Criteria: - Male or female patients ≥ 18 years of age - Patients undergoing elective surgery (open or laparoscopic technique) under general anaesthesia, expected to last at least one hour from induction of anaesthesia to wound closure and expected to require at least one overnight stay in hospital Exclusion Criteria: - Patients scheduled for outpatient/day case surgery - Patients scheduled to undergo intra-thoracic, transplant or central nervous system surgery - Patients scheduled to receive only a local anaesthetic/regional neuraxial (intrathecal or epidural) block - Patients who are expected to remain ventilated for a period after surgery - Patients who are expected to need a naso- or orogastric tube in situ after surgery is completed ; PRIMARY OUTCOME: Number of Participants With Complete Response; SECONDARY OUTCOME 1: Number of Participants With no Nausea.

Yes

TRIAL NAME: Phase II - Non-G1 HCV; BRIEF: The primary objectives of the study are to evaluate the safety, tolerability, and efficacy of voxilaprevir (VOX) plus sofosbuvir/velpatasvir (SOF/VEL) fixed dose combination (FDC) in adults with chronic non genotype 1 hepatitis C virus (HCV) infection. ; DRUG USED: Vosevi; DRUG CLASS: New Molecular Entity (NME); INDICATION: Hepatitis C (HCV) (Antiviral); TARGET: HCV Polymerase (NS5B) - Allosteric binding sites (Non-nucleosides), HCV Protease, Non-structural 5A protein (NS5A); THERAPY: Combination; LEAD SPONSOR: Gilead Sciences; CRITERIA: Key Inclusion Criteria: - Individuals with chronic HCV infection - HCV RNA ≥10^4 IU/mL at screening - HCV genotypes 2, 3, 4, 5, or 6 - Cirrhosis determination; a liver biopsy may be required - Screening laboratory values within defined thresholds - Use of two contraception methods if female of childbearing potential or sexually active male Key Exclusion Criteria: - Pregnant or nursing female - Current or prior history of hepatic decompensation - Hepatocellular carcinoma (HCC) or other clinically significant malignancy - Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) - History of clinically significant illness or any other medical disorder that may interfere with the individual's treatment, assessment or compliance with the protocol NOTE: Other protocol defined Inclusion/Exclusion criteria may apply. ; PRIMARY OUTCOME: Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12); SECONDARY OUTCOME 1: Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)

Yes

TRIAL NAME: Phase II - BRCA1/BRCA2 Wild-Type Patients; BRIEF: The aim of this single-arm phase 2 clinical trial is to evaluate the anti-cancer activity of Talazoparib (also known as BMN 673) in patients with advanced breast cancer with specific genetic or tumor genomic alterations. Patients with either triple-negative or HER2-negative breast cancer are eligible. ; DRUG USED: Talzenna; DRUG CLASS: New Molecular Entity (NME); INDICATION: Breast Cancer; TARGET: Poly ADP-Ribose Polymerase (PARP); THERAPY: Monotherapy; LEAD SPONSOR: Melinda Telli; CRITERIA: INCLUSION CRITERIA: - No deleterious germline BRCA1 or BRCA2 mutation based on full sequencing and comprehensive rearrangement testing at an external reference laboratory; patients with variants of unknown significance will be eligible - Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 - Must have progressed on at least 1 prior chemotherapy regimen for the treatment of advanced breast cancer; there is no upper limit on the number of prior therapies - If prior platinum agent (eg, carboplatin or cisplatin) has been administered, no evidence of progression, or within 8 weeks of stopping platinum treatment - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 - Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN); if liver function abnormalities are due to hepatic metastasis, then AST and ALT ≤ 5 x ULN - Total serum bilirubin ≤ 1.5 x ULN (≤ 3 x ULN for Gilbert's syndrome) - Calculated creatinine clearance ≥ 30 mL/min or serum creatinine ≤ 1.5 mg/dL - Hemoglobin ≥ 9.0 g/dL with last transfusion at least 14 days before day 1 of study drug - Absolute neutrophil count (ANC) ≥ 1500/mm^3 - Platelet count ≥ 100,000/mm^3 - Able to take oral medications - Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures - Sexually active patients of childbearing potential must be willing to use an acceptable method of contraception such as an intrauterine device or double barrier contraception during treatment and for 30 days after the last dose of study drug - Females of childbearing potential must have a negative serum pregnancy test at screening and be willing to have additional serum pregnancy tests during the study; females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to screening, or who have had total hysterectomy - Willing and able to comply with all study procedures - COHORT A SPECIFIC ELIGIBILITY CRITERIA: - Histologically-confirmed metastatic or recurrent triple-negative breast cancer (defined as estrogen receptor ≤ 5%, progesterone receptor ≤ 5%, HER2-negative via immunohistochemistry [IHC] or fluorescent in situ hybridization [FISH]) - An homologous recombination deficiency (HRD) score ≥ 42 on the HRD Assay as assessed on a tumor biopsy sample; in the case that obtaining an adequate metastatic tumor biopsy is not possible, we will assess the HRD score from the primary breast tumor - COHORT B SPECIFIC ELIGIBILITY CRITERIA: - Histologically-confirmed metastatic or recurrent HER2-negative (via IHC or FISH) breast cancer or other histologically-confirmed metastatic solid tumor - Deleterious germline or somatic mutation implicated in the homologous recombination (HR) pathway, excluding BRCA1 or BRCA2, based on germline multiplex gene testing or direct tumor next generation DNA sequencing. Genes of interest include: PTEN, PALB2, CHEK2, ATM, NBN, BARD1, BRIP1, RAD50, Rad51c, Rad51d, MRE11, ATR, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, plus other HR-related genes at the discretion of the primary investigators. EXCLUSION CRITERIA: - Any patient with a deleterious mutation in BRCA1 or BRCA2 - Hormone receptor positive and/or HER2 positive breast cancer (Cohort A only) - HER2 positive breast cancer (Cohort B only) - Prior treatment with a PARP inhibitor - Non-measurable disease only - Pregnant or nursing patients - Any anti-cancer therapy within the past 21 days of the first day of treatment - Brain or central nervous system (CNS) metastases - Exception: Adequately treated brain metastases documented by baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan that have not progressed since previous scans and do not require corticosteroids (except prednisone ≤ 5 mg/day or equivalent) for management of CNS symptoms. A repeated CT or MRI following the identification of CNS metastases (obtained at least 2 weeks after definitive therapy) must document adequately treated brain metastases - Subjects with leptomeningeal carcinomatosis are not permitted - Other malignancy that is either active or for which patient has received treatment in the last five years excluding non-melanoma skin cancer and carcinoma in situ of the cervix - Radiation therapy in the last 14 days - Known to be human immunodeficiency virus positive - Known active hepatitis C virus - Known active hepatitis B virus - Use of any investigational product or investigational medical device within 28 days before day 1 of study drug - Major surgery requiring a prolonged hospitalization or recovery within 21 days before day 1 of study drug - Concurrent disease or condition that would interfere with study participation or safety, such as any of the following: - Active, clinically significant infection either grade > 2 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 or requiring the use of parenteral anti-microbial agents within 7 days before day 1 of study drug - Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders - Known hypersensitivity to any of the components of BMN 673 ; PRIMARY OUTCOME: Objective Response (OR); SECONDARY OUTCOME 1: Clinical Benefit (CB)

Yes

TRIAL NAME: Phase I - NI-AC006 (Healthy Volunteers); BRIEF: This is a 2 week Phase 1 study of SB204 (NVN1000 Gel) in healthy adult volunteers with elevated Propionibacterium acnes (P. acnes) counts. Subjects will apply NVN1000 4% Gel or Vehicle Gel twice daily to their face. Assessments will include cutaneous tolerability, safety, and P. acnes counts. ; DRUG USED: SB204; DRUG CLASS: New Molecular Entity (NME); INDICATION: Acne; TARGET: Nitric Oxide/ Nitrogen Monoxide; THERAPY: Monotherapy; LEAD SPONSOR: Novan, Inc.; CRITERIA: Inclusion Criteria: - Healthy adult male or female volunteers - If a woman of child-bearing potential, agrees to use effective method of birth control during the study and for 30 days after the final study visit - Agree to refrain from use of antimicrobial topical products during study Exclusion Criteria: - Any skin disorders of acute or chronic nature including psoriasis, eczema, etc - Female subjects who are pregnant, nursing, or planning to become pregnant - Subjects who have used topical or systemic antibiotics, estrogens, drugs associated with methemoglobinemia, nitrate donors - Subjects with baseline methemoglobin > 2% - Subjects with clinically significant anemia ; PRIMARY OUTCOME: Tolerability based on the cutaneous tolerability scores; SECONDARY OUTCOME 1: Safety which includes reported adverse events, clinically significant changes in physical exam, and labs

Yes

TRIAL NAME: Phase I - Safety; BRIEF: This study will evaluate the safety, tolerability, and pharmacokinetics (PK) of PBI-4547 in healthy adult participants. ; DRUG USED: PBI-4547; DRUG CLASS: New Molecular Entity (NME); INDICATION: Non-Alcoholic Steatohepatitis (NASH); TARGET: GPR40 (FFAR1, free fatty acid receptor 1), GPR84; THERAPY: Monotherapy; LEAD SPONSOR: Liminal BioSciences Ltd.; CRITERIA: Inclusion Criteria: - Healthy male participants or non-childbearing potential female participants, ≥18 and ≤55 years. - Body mass index > 18.5 and < 30.0 kg/m^2, and body weight ≥ 50.0 kg for male participants and ≥ 45.0 kg for female participants. - Continuous non-smoker who has not used tobacco or nicotine-containing products for at least 3 months prior to screening. - Male participants with a pregnant partner must agree to use a condom from the first dosing until at least 90 days after study drug administration. - Male participants must be willing not to donate sperm until 90 days after study drug administration. Exclusion Criteria: - Any clinically significant abnormality or abnormal laboratory test results. - An estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m^2. - Positive urine drug screen and history of significant drug abuse. - History of significant allergic reactions to any drug. - Use of any drugs known to induce or inhibit hepatic drug metabolism. - Positive pregnancy test or breast-feeding participant. - Clinically significant abnormalities in ECG, blood pressure, and heart rate at screening. - History of significant alcohol abuse or regular use of alcohol. - Use of medication other than topical products without significant systemic absorption. - Donation of plasma. ; PRIMARY OUTCOME: Number of participants with treatment-emergent adverse events (TEAEs); SECONDARY OUTCOME 1: AUC0-t for PBI-4547

No

TRIAL NAME: Phase I - 0201 (Australia); BRIEF: Preliminary Evaluation of Safety, Tolerability, and Efficacy of XT-150 for the Treatment of Osteoarthritic Pain - Dose escalation ; DRUG USED: XT-150; DRUG CLASS: Biologic; INDICATION: Osteoarthritis and Osteoarthritis Pain; TARGET: IL-10 (Interleukin-10) and IL-10 Receptor (IL-10R); THERAPY: Monotherapy; LEAD SPONSOR: Xalud Therapeutics, Inc.; CRITERIA: Inclusion Criteria: 1. Male or female, between 18 and 90 years of age, inclusive. Women who are not of child-bearing potential in the same age range. 2. Sufficiently severe OA of knee to require/have recommended knee replacement surgery or be unsuitable for knee replacement surgery or be unsuitable for knee replacement surgery based on co-morbidities or orthopedic considerations; be free of local or intra-articular infection. 3. Symptomatic disease because of osteoarthritis, defined as one or more of the following Verbal Numerical Rating Scale (VNRS) scores: 1. a worst pain of at least 7 at any time during the preceding week (based on scale of 0 to 10, with 10 representing "pain as bad as you can imagine"). 2. a worst stiffness of at least 7 at any time during the preceding week (based on a scale of 0 to 10, with 10 representing "stiffness as bad as you can imagine"). 4. Stable analgesic regimen during the 4 weeks prior to enrollment. 5. Inadequate pain relief (mean >5 mean on Brief Pain Inventory-Severity Scale) from prior therapies lasting 3 months. 6. In the judgment of the Investigator, acceptable general medical condition 7. Life expectancy >6 months 8. Male participants who are heterosexually active and not surgically sterile must agree to use effective contraception, including abstinence, for the duration of the study and for 3 months after the study is completed. 9. Have suitable knee joint anatomy for intra-articular injection 10. Willing and able to return for the follow-up (FU) visits 11. Able to reliably provide pain assessment 12. Able to read and understand study instructions, and willing and able to comply with all study procedures Exclusion Criteria: 1. Hypersensitivity, allergy, or significant reaction to any ingredient of the study drug, including double-stranded DNA, mannose, and sucrose 2. Scheduled knee replacement within 4 months; participant agrees not to schedule a knee replacement appointment within 4 months of study treatment 3. History of rheumatoid arthritis of the knee 4. High peri-operative risks which in the judgment of the investigator preclude a safe knee injection procedure (e.g., poorly controlled diabetes, cardiac inadequacy such as NYHA class > II, G4 glomerular filtration rate [eGFR < 30 mL/min by Cockcroft-Gault]) 5. Current treatment with immunosuppressive (systemic corticosteroid therapy [equivalent to >10mg/day prednisone] or other strong immunosuppressant) 6. History of immunosuppressive therapy; high-potency systemic steroids in the last 3 months. 7. Currently receiving systemic chemotherapy or radiation therapy for malignancy 8. Clinically significant hepatic disease as indicated by clinical laboratory results ≥3 times the upper limit of normal for any liver function test (e.g., aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase) 9. Severe anemia (Grade 3; hemoglobin <8.0 g/dL, <4.9 mmol/L, <80 g/L; transfusion indicated), uncontrolled coagulopathy (Grade 1, prolonged activated partial prothrombin time (aPTT) > upper limit of normal (ULN) to 1.5xULN), or bleeding diathesis, Grade 1 white cell counts (lymphocytes <LLN - 800/mm3; <LLN - 0.8 x 10e9 /L, neutrophils <LLN - 1500/mm3; <LLN - 1.5 x 10e9 /L) 10. Positive serology for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus within 4 weeks of commencing the study 11. Significant neuropsychiatric conditions; dementia, major depression, or altered mental state that in the opinion of the Investigator will interfere with study participation 12. Current treatment with systemic antibiotics or antivirals (EXCEPTION: topical treatments) 13. Current treatment with anticoagulants, other than low-dose aspirin, prescribed for new onset of symptoms in 3 months before screening visit. 14. Known or suspected history of active alcohol or intravenous/oral drug abuse within 1 year before the screening visit 15. Women of child-bearing potential 16. Use of any investigational drug or device within 1 month before enrollment or current participation in a trial that included intervention with a drug or device; or currently participating in an investigational drug or device study. 17. Any condition that, in the opinion of the Principal Investigator, could compromise the safety of the participant, the participant's ability to communicate the study staff, or the quality of the data ; PRIMARY OUTCOME: Incidence of Treatment-Emergent Adverse Events [Safety]; SECONDARY OUTCOME 1: Verbal Numerical Rating Scale

Yes

TRIAL NAME: Phase II - Diabetics; BRIEF: GSK962040 is a novel small molecule motilin agonist. The Phase I studies (MOT107043 and MOT109681) demonstrated that single doses of GSK962040 up to 150 mg and repeat dosing of up to 125 mg/day for 14 days were well tolerated with adverse events not occurring in greater prevalence than placebo, and no significant abnormal vital sign, ECG, or clinical laboratory findings. Pharmacokinetic parameters were linear and approximately dose proportional over the range of doses administered. Single doses of 50 mg - 150 mg GSK962040 significantly increased the rate of gastric emptying up to 40% as measured by the 13C octanoic acid stable isotope breath test. A similar effect of 50 mg and 125 mg on gastric emptying was observed throughout repeated dosing to healthy volunteers for 14-days. The aims of the present investigation (MOT114479) are to assess the pharmacodynamic effects (gastric emptying and symptoms), safety, tolerability, and pharmacokinetics of GSK962040 after 28 days of once-daily dosing in Type I and Type II diabetic subjects with gastroparesis. An additional aim is to characterize the dose/exposure - pharmacodynamic effect relationship. ; DRUG USED: Camicinal; DRUG CLASS: New Molecular Entity (NME); INDICATION: Diabetic Gastroparesis; TARGET: Motilin / Motilin Receptor (MTLR or GPR38); THERAPY: Monotherapy; LEAD SPONSOR: GlaxoSmithKline; CRITERIA: Inclusion Criteria: - Type I or II Diabetes Mellitus (HbA1C < 10%) - Male or female between 18 and 80 years of age, inclusive. - Patient has gastroparesis at screening (gastric half-time of emptying > upper limit of normal as determined by 13C-oral breath test) - Patient must have a > or = 3 month history of relevant symptoms of gastroparesis (e.g., chronic post-prandial fullness, early satiety, postprandial nausea), patients will have a mean of the daily scores over a minimum of 7 days indicating > or = mild (2) and < or = severe (4) post-prandial fullness assessed using the GCSI-DD during the screening period prior to randomization. - A female patient is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/mL, or a value consistent with the local laboratory standard value, is confirmatory. OR Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female patients must agree to use contraception for at least 5 days following the last dose of study medication. - Male patients must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication through at least 5 days after the last dose of study medication. - BMI >18 and < or = 35.0 kg/m2 (inclusive). - Patient has never had a gastrectomy, nor major gastric surgical procedure or any evidence of bowel obstruction or strictures within the previous 12 months - Dosage of any concomitant medications has been stable for at least 3 weeks, except for routine adjustments in daily insulin treatments. - Estimated (or measured) glomerular filtration rate > or = 30 mL/min. - QTcB or QTcF < 450 msec or QTc < 480 msec in patients with Bundle Branch Block based on single or average QTc value of triplicate values obtained over a brief recording period. - Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. - AST and ALT < 2xULN; alkaline phosphatase and bilirubin < or = 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). Exclusion Criteria: - Patient has acute severe gastroenteritis - Patient has a gastric pacemaker - Patient is on chronic parenteral feeding - Patient has pronounced dehydration - Recent (last 6 weeks) history of poor control of diabetes e.g. hypoglycaemia requiring medical intervention, diabetic ketoacidosis, admission for control diabetes or complications of diabetes - Patient has evidence of severe cardiovascular autonomic neuropathy (e.g. history of recurrent syncope in the last 6 months) - Patient has a history of eating disorders (anorexia nervosa, binge eating, bulimia) - Use of medications potentially influencing upper gastrointestinal motility or appetite within one week of the study (e.g., prokinetic drugs, macrolide antibiotics (erythromycin), GLP-1 mimetics) - Regular opiate use - Use of prohibited medications listed in Section 9.2 within the restricted timeframe relative to the first dose of study medication. - History or presence of clinically significant gastro-intestinal, hepatic or renal disease or other condition that would in the opinion of the investigator or medical monitor make the subject unsuitable for inclusion in this clinical study. - The patient has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). - History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. - Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day time-period. - Pregnant females as determined by positive serum or urine hCG test (from the first urine of the day) at screening or prior to dosing. - Lactating females. - Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). - A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening ; PRIMARY OUTCOME: Gastric Half Emptying Time (GEt1/2); SECONDARY OUTCOME 1: Number of Participants With On-treatment Adverse Events (AES) and Serious Adverse Events(SAEs)

No

TRIAL NAME: Phase II/III - EP0060 (4-17 y.o.) ; BRIEF: EP0060 is a multicenter, open-label study to evaluate the safety and tolerability of intravenous (iv) Lacosamide (LCM) in pediatric subjects >= 1 month to < 17 years of age with epilepsy. ; DRUG USED: Vimpat; DRUG CLASS: New Molecular Entity (NME); INDICATION: Partial Seizures (Epilepsy); TARGET: Collapsin Response Mediator Protein 2 (CRMP-2), Sodium Channels; THERAPY: Monotherapy; LEAD SPONSOR: UCB BIOSCIENCES, Inc.; CRITERIA: Inclusion Criteria: - Male or female from >=1 month to <17 years of age - Subject has a diagnosis of epilepsy with partial-onset seizures or primary generalized tonic-clonic seizures - Subject meets 1 of the following criteria: 1. Open-label lacosmide (OLL) subject: Subject is currently receiving oral lacosmide (LCM) as adjunctive or monotherapy as participants in an open label long-term study (SP848, EP0034, or other pediatric study); OR, 2. Prescription lacosamide (RxL) subject: Subject is currently receiving prescribed oral LCM from commercial supply (eg, VIMPAT) as adjunctive or monotherapy; OR, 3. Initiating intravenous lacosamide (IIL) subject: Subject is not currently receiving LCM and will receive intravenous (iv) LCM as adjunctive treatment in EP0060. Initiation of LCM monotherapy is not permitted in IIL subjects. - Subject is an OLL or RxL subject and meets both of the following criteria: 1. Subject has been administered LCM for the treatment of epilepsy for at least 2 weeks prior to Screening; AND 2. Subject has been administered (OLL) or prescribed (RxL) oral LCM at a dose of 2 mg/kg/day to 12 mg/kg/day (for subjects <50 kg) or 100 mg/day to 600 mg/day (for subjects >=50 kg). Open-label study drug LCM (OLL) or prescribed oral LCM dose (RxL) must be stable for at least 3 days prior to first LCM infusion; OR, - Subject is an ILL subject and is on a stable dosage regimen of at least 1 antiepileptic drug (AED). The daily dosage regimen of concomitant AED therapy must be kept constant for a period of at least 2 weeks prior to Screening. - Subject is an acceptable candidate for venipuncture and iv infusion - Subject is, in the opinion of the investigator, able to comply with all study requirements. Subject (or parent[s] or legal representative) is willing to comply with all study requirements - Subject weighs >=4 kg Exclusion Criteria: - Subject has previously received intravenous (iv) lacosamide (LCM) in this study - Subject has any medical, neurological, or psychiatric condition that, in the opinion of the investigator, could jeopardize the subject's health or compromise the subject's ability to participate in EP0060 - Subject has clinically significant hypotension or bradycardia in the opinion of the investigator - Subject >=6 years of age has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by positive responses ("Yes") to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening For open-label lacosamide (OLL) subjects, enrollment in EP0060 is not permitted if any of the following additional criteria are met: - Subject has any ongoing Adverse Event (AE) in their long-term, open-label study that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate EP0060 or the subject meets any of the criteria for required withdrawal from the long-term open-label study For prescription lacosamide (RxL) and initiating intravenous lacosamide (IIL) subjects, enrollment in EP0060 is not permitted if any of the following additional criteria are met: - Subject has a medical condition that could reasonably be expected to interfere with drug absorption distribution, metabolism, or excretion - Subject is a female of childbearing potential and does not practice an acceptable method of contraception for the duration of participation in EP0060 - Subject has creatinine clearance less than 30 mL/min - Subject has a clinically relevant electrocardiogram (ECG) abnormality, in the opinion of the principal investigator (ie, second or third degree heart block at rest or a QT prolongation greater than 450 ms) - Subject has hemodynamically significant heart disease (eg, heart failure) - Subject has an arrhythmic heart condition requiring medical therapy, known cardiac sodium channelopathy, such as Brugada syndrome - Subject has a known history of severe anaphylactic reaction or serious blood dyscrasias - Subject has an acute or subacutely progressive central nervous system disease. - Subject has epilepsy secondary to a progressing cerebral disease or any other progressive or neurodegenerative disease (malignant brain tumor or Rasmussen syndrome) - Lacosamide is intended for treatment of generalized convulsive status epilepticus - Subject has diagnosis of Dravet's syndrome For IIL subjects, enrollment in EP0060 is not permitted if the following additional criterion is met: - Subject has been treated with LCM within the last 3 months prior to Screening ; PRIMARY OUTCOME: Percentage of Participants With at Least One Adverse Event Reported Spontaneously by the Participant/or Caregiver (Including Parent/Legal Guardian) or Observed by the Investigator During the Study; SECONDARY OUTCOME 1:

Yes

TRIAL NAME: Phase I - C22001; BRIEF: Overview of Study Design: This is a phase 1, multicenter, open-label, multiple-dose, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of TAK-960 in patients with advanced nonhematologic malignancies. This study will be the first to administer TAK-960 to humans. The patient population will consist of adults with a nonhematologic malignancy for which standard treatment is no longer effective or does not offer curative or life-prolonging potential, or for which no standard treatment is available. ; DRUG USED: TAK-960; DRUG CLASS: New Molecular Entity (NME); INDICATION: Solid Tumors; TARGET: Polo-like kinase 1 (Plk1); THERAPY: Monotherapy; LEAD SPONSOR: Millennium Pharmaceuticals, Inc.; CRITERIA: Inclusion Criteria: Each patient must meet all of the following inclusion criteria to be enrolled in the study: - Male or female 18 years or older - Clinical laboratory values as specified in protocol - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Histologically and/or cytologically confirmed diagnosis of metastatic, unresectable, advanced evaluable nonhematologic malignancy for which standard treatment is not available or no longer effective - Radiographically or clinically evaluable tumor - Suitable venous access for study-required blood sampling - Female patients who are postmenopausal, surgically sterile or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse - Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse - Voluntary written consent - Willing to undergo biopsy procedures (expansion phase only) - Weight at least 40 kg - Recovered from the reversible effects of prior antineoplastic therapy to Grade ≤ 1 or to patient's baseline values, excluding alopecia Exclusion Criteria: Patients meeting any of the following exclusion criteria are not to be enrolled in the study: - Diagnosis of primary central nervous system malignancy or carcinomatous meningitis - Patient has symptomatic brain metastasis. Patients with brain metastases must: have stable neurologic status for at least 2 weeks following completion of local therapy AND be without neurologic dysfunction that would confound the evaluation of adverse events - Prior allogeneic bone marrow or stem cell transplant - Prior therapy or treatment as specified in protocol - Female patients who are lactating or who have a positive serum pregnancy test during the screening period of within 3 days before the first dose of TAK-960 - Myocardial infarction within 6 months before first dose of TAK-960 - Any of the cardiovascular conditions or values as specified in the study protocol within 6 months before the first dose of TAK-960 - Infection requiring systemic anti-infective therapy within 14 days before the start of TAK-960, or other severe infection - Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive or known suspected active hepatitis C infection - A diagnosis of or treated for another malignancy within 2 years before the first dose of TAK-960 or previous diagnosis of another malignancy and any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection - Any serious medical or psychiatric illness that could potentially interfere with the completion of treatment - Recurrent nausea or vomiting or requirement for antiemetic therapy within 14 days before the first dose of TAK-960 - Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerability of TAK-960, including difficulty swallowing capsules - Treatment with any investigational products within 21 days before the first dose of TAK-960 - Systemic use of strong CYP3A inhibitors or inducers within 14 days before the first dose of TAK-960 - Patients enrolled in the expansion cohorts where tumor biopsies are required must meet additional criteria according to the study protocol ; PRIMARY OUTCOME: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of TAK-960; SECONDARY OUTCOME 1:

No

TRIAL NAME: Phase Ia/b - Study 003 (w/Nivolumab); BRIEF: Phase 1a/1b does-escalation study of cabiralizumab alone and with nivolumab in advanced solid tumors. ; DRUG USED: Cabiralizumab; DRUG CLASS: Biologic; INDICATION: Solid Tumors; TARGET: Macrophage Colony Stimulating Factor 1 (M-CSF1)/M-CSF Receptor/FMS/CD115/CSF-1/CSF1R; THERAPY: Combination; LEAD SPONSOR: Five Prime Therapeutics, Inc.; CRITERIA: Inclusion Criteria: - Patients must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. - Patients must have had progressive disease on, after, or refused, appropriate approved therapy for their tumor type. - Patients must have histologically or cytologically confirmed solid tumor that is locally recurrent or metastatic and has progressed following standard treatment or is not appropriate for standard treatment - Understand and sign an Institutional review board/Independent ethics committee (IRB/IEC)-approved informed consent form (ICF) prior to any study-specific evaluation - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Willing and able to comply with all study procedures Exclusion Criteria: - Current or history of clinically significant muscle disorders (e.g., myositis), recent unresolved muscle injury, or any condition known to elevate serum creatine kinase (CK) levels - Decreased cardiac function with New York Heart Association (NYHA) > Class 2 - Uncontrolled or significant heart disorder such as unstable angina - Significant abnormalities on electrocardiogram (ECG) at screening. Fridericia's correction formula for QT interval (QTcF) > 450 msec for males or > 470 msec for females at screening - History of anti-drug antibodies, severe allergic, anaphylactic, or other infusion-related reaction to a previous biologic agent - Positive test for latent tuberculosis (TB) at screening (Quantiferon test) or evidence of active TB - Patients with abnormal serum chemistry values, which in the opinion of the Investigator is considered to be clinically significant, will be excluded from the study - Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples - Any uncontrolled medical condition or psychiatric disorder which, in the opinion of the Investigator, would pose a risk to patient safety or interfere with study participation or interpretation of individual patient results - Pregnant or breastfeeding - Current unresolved infection or history of chronic, active, clinically significant infection (viral, bacterial, fungal, or other) which, in the opinion of the Investigator, would preclude the patient from exposure to a biologic agent or pose a risk to patient safety - Prior exposure to any colony stimulating factor 1 receptor (CSF1R) pathway inhibitors ; PRIMARY OUTCOME: Safety: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (Phase 1a); SECONDARY OUTCOME 1: Efficacy: Overall Survival (Phase 1b)

No

TRIAL NAME: Phase I - CL12001 (Finland); BRIEF: Indicated for the Treatment of Secondary Lymphedema Associated with the Treatment of Breast Cancer. Primary objective is to evaluate the safety and tolerability of a single dose of Lymfactin® in patients with secondary lymphedema associated with the treatment of breast cancer. ; DRUG USED: Lymfactin; DRUG CLASS: Biologic; INDICATION: Edema; TARGET: VEGF (Vascular endothelial growth factor); THERAPY: Monotherapy; LEAD SPONSOR: Herantis Pharma Plc.; CRITERIA: Inclusion criteria: 1. Female patients with secondary lymphedema associated with the treatment of breast cancer. 2. Patient who understands and voluntarily signs informed consent prior to any screening procedure. 3. 18 - 70 years of age. 4. BMI between 18 and 32 inclusive. 5. Female patients with secondary lymphedema in the arm associated with breast cancer who: 1. Have undergone sentinel lymph node biopsies and/or lymph node resection in the axilla on the affected side of their breast cancer with initial N1 staging and lymph node metastasis in ≤ three lymph nodes. 2. Require garment use as a compression treatment for the lymphedema in the affected arm. 3. Have the volume of the affected arm at least 10% greater than the unaffected arm following 7 days after removal of the compression garments. 4. Have the presence of pitting edema in the affected arm without compression garments. 6. No evidence of recurrent or active breast cancer at least 2 years and no more than 5 years after breast cancer surgery and/or the end of chemotherapy and/or radiotherapy (excluding endocrine and/or aromatase inhibitor treatment). PET CT scan of the chest and the abdomen within 45 days of treatment with Lymfactin® without signs of active breast cancer or any other malignancy. 7. Patient with the following laboratory values: 1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the institutional upper limit of normal (ULN) 2. Bilirubin ≤ 1.5 mg/dL 3. PT and PTT ≤ 1.5 times the ULN 4. Serum creatinine ≤ 2 mg/dL 5. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm³ 6. Platelet count ≥ 100,000/mm³ 7. Hemoglobin ≥ 10 g/dL 8. Willingness to comply with scheduled visits, laboratory assessments, and other study-related procedures due to the regulatory requirements related to gene based therapies. 9. Non-smoker or willing to stop smoking or using nicotine-containing products for at least 4 weeks prior to entry to study. 10. Negative urine pregnancy test (only patients with childbearing potential) at screening and use of adequate contraceptive measures from screening until 6 months after the study treatment administration: 1. A patient with childbearing potential should be using a reliable contraception method: intrauterine device (hormonal or non-hormonal); oral combination pill or hormonal contraception patch; or two of the following: intra-vaginal hormonal ring, oral contraceptive containing progestin only, spermicidal foam, condom, sterilization of male sexual partner (surgical vasectomy). 2. A patient with no current heterosexual relationship may be included according to the judgement of the Investigator. 3. If the patient is surgically sterile or whose menopause occurred 2 years previously at the minimum, no contraception is required nor pregnancy test. Exclusion criteria: 1. A patient who had an N2/N3 or a T4 stage breast cancer or an inflammatory breast cancer at the time of the original diagnosis. 2. A patient with evidence (clinical, laboratory, or imaging) or history of a neoplasm other than breast cancer (except basal cell carcinoma or cervical in situ carcinoma). 3. A patient known to be pregnant, lactating or having a positive or indeterminate pregnancy test. 4. Treatment with COX-2 inhibitors should be interrupted from one week prior until 2 weeks post surgery and treatment with Lymfactin®. 5. Previous treatment with, or participation in, trial of a gene therapy product. 6. Current participation or participation in the preceding two months, in any clinical study apart from a noninterventional study. 7. Current treatment with immunosuppressive drugs. 8. Current or history of drug, including nicotinecontaining products, or alcohol abuse. 9. Known human immunodeficiency virus- or acquired immunodeficiency syndrome-related illness. 10. Allergy to any ingredients of the Lymfactin® solution for injection (glycerol, N-2-hydroxyethylpiperazine-N´-2-ethanesulfonic acid (HEPES), sodium hydroxide). 11. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, that would affect the patient's ability to follow study-related procedures, or that may interfere with the interpretation of study results and, in the Investigator's opinion, would make the patient inappropriate for entry into this study. 12. Doubtful availability, in the opinion of the Investigator, to complete the study. ; PRIMARY OUTCOME: Safety as measured by number of patients with treatment related adverse events and serious adverse events as assessed by CTCAE v4.0; SECONDARY OUTCOME 1: Measurement of the volume of the arms

No

TRIAL NAME: Phase Ib/II - w/Palbociclib; BRIEF: This is a multi-center, open-label, phase Ib/II study of APG-2575 as a single agent in patients with advanced solid tumors or in combination with anti-cancer agents such as CDK 4/6 inhibitor palbociclib in patients with ER+/HER2- metastatic breast cancer (mBC) who have progressed or relapsed after first line therapy ; DRUG USED: APG-2575; DRUG CLASS: New Molecular Entity (NME); INDICATION: Solid Tumors; TARGET: B-cell lymphoma 2 (Bcl-2)/Bcl-2 Family; THERAPY: Monotherapy and Combo Therapy; LEAD SPONSOR: Ascentage Pharma Group Inc.; CRITERIA: Inclusion Criteria: Age ≥ 18 years. 2. Histologically or cytologically confirmed solid tumors; These locally advanced or metastatic diseases have no standard effective therapy available as judged by the investigator. 3. For the patients with breast cancer: 1. Must have histological or cytological confirmation of metastatic carcinoma of the breast (either from the primary or metastatic site), with the following tumor molecular characteristics (as determined from pre-screening testing): 1. ER positive. 2. HER2 negative - non-amplified (per ASCO/CAP guidelines). 2. Must have been treated with CDK4/6 inhibitor in the metastatic setting. And the patients must have experienced disease progression during or recurrence after CDK4/6 inhibitor therapy, which must have been administered for a minimum of 8 weeks prior to progression. 3. Must have measurable disease (according to RECIST v1.1) or evaluable disease. Boneonly metastases are allowed. 4. Physiological postmenopausal, defined as: 1. Age ≥60 years, or 2. Age <60 years and undergone bilateral oophorectomy or medically confirmed ovarian failure, or 3. Age <60 years and have cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have serum levels of estradiol and FSH within the reference range for postmenopausal females. 4. Premenopausal treated with LHRH analogues APG2575XU103 Version 1.0. / March 8, 2021 APG-2575 Ascentage Pharma Group Inc. Confidential Page 51 of 108 4. ECOG ≤ 1. 5. Adequate organ and bone marrow function within 14 days prior to registration: 1) Hemoglobin ≥ 90 g/L. 2) Absolute neutrophil count ≥ 1.5 x 109 - L. Note: Use of growth-factors to maintain ANC criterion is not permitted 3) Platelet count ≥ 100 x 109 - L. Note: Use of transfusions or thrombopoietic agents to achieve baseline platelet count criterion is prohibited. 4) ALT and AST ≤ 3 x upper limit of normal (ULN), or ≤ 5 x ULN if liver metastases are present. 5) Total serum bilirubin ≤ 1.5 x ULN. Patient's with Gilbert's syndrome may have a total serum bilirubin > 1.5 x ULN. 6) Serum creatinine ≤ 1.5 x upper limit of normal (ULN); if serum creatinine is >1.5 X ULN, creatinine clearance must be ≥ 50 mL/min (Cockcroft-Gault). 6. Female patients with childbearing potential must have negative urine or serum pregnancy test within 14 days prior to registration. 7. Able to swallow whole tablets. 8. Willingness to use contraception that is deemed effective for the patients with child bearing potential (postmenopausal women must have been amenorrhea for at least 12 months to be considered of non-childbearing potential) and their partners throughout the treatment period and for at least three months following the last dose of study drug. 9. Brain metastases with clinically controlled neurologic symptoms. 10. Able to sign written informed consent with willingness and ability to comply with study procedures and follow-up examination. 11. Patient assigned to combination therapy, must provide sufficient archival tumor lesion or willing to provide fresh biopsy if no archival tissue available and core or excisional biopsy of a tumor lesion where feasible. Patients cannot provide a fresh biopsy (e.g. inaccessible or patient safety concern) may be eligible upon agreement from the sponsor. - Exclusion Criteria: - Receive any anti-cancer therapy within 14 days prior to the first dose of study drug, including chemotherapy, radiation therapy, surgery, targeted therapy, steroid therapy, endocrine therapy or other investigational therapy with the exception of hormones for hypothyroidism or estrogen replacement therapy (ERT) for non-breast cancer patients, or has had tumor embolization. Patients must have a 5x half-lives wash out time period or 14 for small molecules or 28 days for biologics including IO agents, gene or cellular therapeutic agents, respectively. These following therapies are permitted: a. Bisphosphonate or denosumab therapy for patients with bone metastases. APG2575XU103 Version 1.0. / March 8, 2021 APG-2575 Ascentage Pharma Group Inc. Confidential Page 52 of 108 b. Ovarian suppression in pre- and peri-menopausal patients. c. Palliative radiotherapy. 2. Receive any following agents within 14 days prior to the first dose of study drugs: 1. Strong CYP3A inhibitors or inducers 2. Drugs that are known to prolong the QT interval. 3. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to < Grade 2, exception being clinically insignificant toxicities of prior chemo/radiation such as lymphocytopenia or electrolyte abnormalities. 4. Pregnant or lactating. 5. Have a major surgery within 28 days from study entry, or have had minor surgery within 7 days of study entry. 6. Active symptomatic pathogenic infection including fungal, bacterial and/or viral infection including, but not limited to, active human immunodeficiency virus (HIV) or viral hepatitis (B or C) or active COVID-19. (Patients that have received a COVID-19 vaccination will be considered as eligible for the study.) 7. Unstable angina, myocardial infarction, or a coronary revascularization procedure within 180 days of study entry. Patients with a QTc ≥ 480 msec (based on the mean value of the triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes 8. Prior use of a Bcl-2 inhibitor. 9. Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study. - ; PRIMARY OUTCOME: DLT; SECONDARY OUTCOME 1:

No

TRIAL NAME: Phase Ib - w/Erlotinib ; BRIEF: This open-label, multicenter study will assess the safety, tolerability, and pharmacokinetics of intravenous (IV) dosing of atezolizumab in combination with oral erlotinib or alectinib in participants with NSCLC. This study has two stages. In the erlotinib group, the combination treatment will be given to participants with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-treatment-naive, advanced (nonresectable) NSCLC in a safety-evaluation stage and to participants with previously untreated EGFR mutation-positive, advanced NSCLC in an expansion stage (Stage 2). In the alectinib group, for both the safety-evaluation and expansion stages (Stages 1 and 2), the combination will be given to participants who are treatment-naive with anaplastic lymphoma kinase (ALK)-positive advanced NSCLC. In Stage 1, erlotinib will be given at a starting dose of 150 milligrams (mg) by mouth (PO) once daily (QD) and the starting dose of alectinib will be 600 mg twice daily (BID), for 28 consecutive days during Cycle 1 and on Days 1 through 21 of each cycle thereafter. The starting dose of atezolizumab will be 1200 mg, administered every 3 weeks (q3W) starting on Day 8 of Cycle 1. If the starting regimen for a combination treatment is not tolerated, alternative doses and/or schedules of erlotinib and atezolizumab or alectinib and atezolizumab may be tested to determine potential recommended Phase 2 dose (RP2D) for that combination treatment. In Stage 2, a potential RP2D and schedule for each combination treatment will be investigated in an expansion cohort. For both stages, continuation of treatment beyond Cycle 1 will be at the discretion of the treating investigator. Study treatment will be discontinued in participants who experience disease progression or unacceptable toxicity, are not compliant with the study protocol, or, in their opinion or in the opinion of the investigator, are not benefiting from study treatment. However, in the absence of unacceptable toxicity, participants with second-line or greater NSCLC who are still receiving atezolizumab at the time of radiographic disease progression may be permitted to continue study treatment. ; DRUG USED: Tecentriq; DRUG CLASS: Biologic; INDICATION: Non-Small Cell Lung Cancer (NSCLC); TARGET: Immune System, Programmed death-1 receptor (PD-1) / Programmed death ligands (PD-L1 and PD-L2); THERAPY: Monotherapy; LEAD SPONSOR: Hoffmann-La Roche; CRITERIA: Inclusion Criteria: - Histologically or cytologically documented, locally advanced or metastatic NSCLC. - Participants in Stage 1 (Safety Evaluation) receiving erlotinib: No limit to the number of prior therapies (except for EGFR TKIs). - Participants in Stage 2 (Expansion) receiving erlotinib: i) sensitizing mutation in the EGFR gene and ii) consent to collection of tumor tissue samples before, during, and after treatment for biopsy and PD biomarker analyses. - Participants receiving alectinib in either Stage 1 or Stage 2: must be ALK positive as assessed by Food and Drug Administration (FDA) approved test and must not have received prior treatment for their advanced NSCLC. - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. - Life expectancy of at least 12 weeks. - Measurable disease, as defined by RECIST Version 1.1 (v1.1). - Adequate hematologic and end-organ function. - Use of highly effective contraception (as defined by protocol) and until 5 months after the last dose of atezolizumab and for 3 months after the last dose of alectinib or for 2 weeks after the last dose of erlotinib, whichever is longer; Males must also refrain from sperm donatation during this same time period. Participants must not be pregnant or breastfeeding. - Archival tumor tissue specimen meeting protocol specifications or the participant will be offered the option of a pre-treatment biopsy to obtain adequate tissue sample. Exclusion Criteria: - For participants receiving erlotinib group: prior treatment with any EGFR mutant-targeting TKI - Any approved anticancer therapy, including chemotherapy, or hormonal therapy (except hormone-replacement therapy or oral contraceptives) within 3 weeks of first dose. - Treatment with any other test drug or participation in another clinical trial within 28 days of enrollment. - Known symptomatic central nervous system (CNS) metastases. Participants with a history of treated or untreated asymptomatic CNS metastases may be eligible. - Leptomeningeal disease. - Uncontrolled tumor-related pain. - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring drainage at least once monthly. - High levels of calcium requiring bisphosphonate therapy or denosumab. - Malignancies other than NSCLC within 5 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death (such as adequately treated carcinoma in-situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ). - History of severe allergic, anaphylactic, or other reactions to chimeric or humanized antibodies or fusion proteins. - Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation. - History of autoimmune disease. - Participants with prior bone marrow or solid organ transplantation. - History of lung inflammation or disease. - Serum albumin less than (<) 2.5 grams per deciliter (g/dL). - Positive for Human Immunodeficiency Virus (HIV). - Liver disease. - Current or active tuberculosis, hepatitis B, or hepatitis C. - Participants with past or resolved hepatitis B virus (HBV) infection are eligible; participants positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV Riboxy Nucleic Acid (RNA). - Signs or symptoms of infection within 2 weeks prior to first dosing. - Received therapeutic oral or IV antibiotics within 2 weeks prior to first dosing. - Significant cardiovascular disease. - Major surgical procedure other than for diagnosis within 28 days prior to first dosing or during the course of the study. - Administration of a live, attenuated vaccine within 4 weeks before first dosing or during the study. - Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that may reasonably prevent the participant from participating. - Hypersensitivity to erlotinib or alectinib or to any of the excipients. - Any significant ophthalmologic abnormality. The use of contact lenses is not recommended during the study. - For participants receiving alectinib: baseline Fridericias corrected QT interval (QTcF) greater than (>) 470 milliseconds (ms) or symptomatic bradycardia. - Prior treatment with CD137 agonists or immune checkpoint blockade therapies. - Treatment with systemic immunostimulatory agents within 6 weeks or five half-lives of the drug, whichever is shorter, prior to first dosing. - Treatment with systemic immunosuppressive medications within 2 weeks prior to first dosing (inhaled corticosteroids and mineralocorticoids are allowed). - Participants who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication are elgible for study after discussion and approval by the Medical Monitor. ; PRIMARY OUTCOME: Percentage of Participants with Dose-Limiting Toxicities (DLTs); SECONDARY OUTCOME 1: Minimum Plasma Concentration (Cmin) of Alectinib and Major Metabolites, as Appropriate

Yes

TRIAL NAME: Phase III - w/PegIntron/RBV (Treatment-Naive, GT1; Asia); BRIEF: The purpose of this study is to estimate the difference in the efficacy between a 16-week treatment regimen of boceprevir (BOC) in combination with peg-intron alpha 2b (P) plus ribavirin (R) (BOC + PR) and a 28-week treatment regimen of BOC + PR in previously untreated participants with chronic hepatitis C (CHC) genotype 1 in Asia who achieve undetectable hepatitis C virus ribonucleic acid (HCV RNA). ; DRUG USED: Victrelis; DRUG CLASS: New Molecular Entity (NME); INDICATION: Hepatitis C (HCV) (Antiviral); TARGET: HCV Protease; THERAPY: Combination; LEAD SPONSOR: Merck Sharp & Dohme LLC; CRITERIA: Inclusion Criteria: - weigh ≥ 40 kg and ≤ 125 kg - have CHC genotype 1 infection - has had a liver biopsy or non-invasive liver fibrosis test that shows no evidence of cirrhosis and hepatocellular carcinoma - must agree that the participant and the participant's partner will each use acceptable methods of contraception for at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study medication, or longer if dictated by local regulations (for a female participant who is of childbearing potential or male participant with female sexual partner who is of childbearing potential) Exclusion Criteria: - participates in any other interventional clinical trial within 30 days of the screening visit in this trial or intends to participate in another interventional clinical trial during participation in this trial - is co-infected with human immunodeficiency virus (HIV) or hepatitis B virus - has evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis - has evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy - has evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC - has evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years - has been previously treated with an interferon or ribavirin regimen or HCV direct acting anti-viral regimen, or treated for hepatitis C with any investigational medication - taking/plans to take significant inducers of inhibitors of Cytochrome P450 3A4 (CYP3A4) substrates 2 weeks prior to start of study medications, or herbal supplements, including but not limited to St. John's Wort 2 weeks prior to start of study medications (Day 1) - has pre-existing psychiatric condition(s) - has a clinical diagnosis of substance abuse - has any known medical condition that could interfere with the participation in and completion of the trial including immunologically-mediated disease, chronic pulmonary disease, or current or history of any clinically significant cardiac abnormalities/dysfunction - is pregnant or nursing (for female participant) or female partner intends to become pregnant (for male participant) ; PRIMARY OUTCOME: Percentage of Participants With Undetectable HCV RNA Who Achieve Sustained Viral Response at Follow-up Week 12 (SVR12) [16-Week Arm vs. 28-Week Arm]; SECONDARY OUTCOME 1: Percentage of Participants With Undetectable HCV RNA Across Treatment

Yes

TRIAL NAME: Phase II - w/Temozolomide and RT; BRIEF: The purpose of this study is to test the safety and effects of a combination of a study drug, Lapatinib, plus the administration of standard radiation therapy and an FDA approved drug Temozolomide (chemotherapy agent) in patients with newly diagnozed glioblastoma Multiforme.Currently, only radiation therapy and Temozolomide chemotherapy are standard treatment for brain cancer.Lapatinib has not been FDA approved for use in brain tumors treatment. It has been approved to be used as a daily treatment with other chemotherapies by the FDA for the treatment of advanced breast cancer. The purpose of this study is to find the answers to the following research questions: 1. Is Lapatinib given twice a week at higher dosages, with radiation therapy and Temozolomide, safe when given to patients with brain tumor? 2. What are the side effects of Lapatinib given twice a week at higher dosages when given with radiation therapy and Temozolomide and how often do they occur? 3. Can Lapatinib, radiation, and Temozolomide be effective in shrinking tumors when given to patients with brain tumors? 4. To determine whether the presence of genetic alterations specific proteins in the tumor samples can predict whether this study drug is effective on the tumor. ; DRUG USED: Tykerb; DRUG CLASS: New Molecular Entity (NME); INDICATION: Brain Cancer (Malignant Glioma; AA and glioblastoma (GBM)); TARGET: EGFR (Epidermal Growth Factor Receptor), HER2/neu or ErbB-2; THERAPY: Combination; LEAD SPONSOR: Jonsson Comprehensive Cancer Center; CRITERIA: Inclusion Criteria: - Patients will be included in the study based on the following criteria: - Patients will have histologically proven intracranial Glioblastoma Multiforme (GBM) or gliosarcoma (GS). This includes treatment-naïve patients with prior tissue diagnoses of lower grade gliomas that have been upgraded to GBM after repeat resection. - Patients must have available archived tissues of 20-30 unstained slides. If frozen tissues are available, at least 200mg would be preferred, but not mandatory for study eligibility. - Use of effective means of contraception (men and women) in subjects of child-bearing potential - Cranial MRI or contrast CT must have been performed within 21 days of study entry. The use of MRI rather than CT is preferred. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement. If the surgical procedure was a resection, cranial MRI or contrast CT performed within 96 hours of resection is preferred but not required. If the surgical procedure was a biopsy only, a head CT within 96 hours of the biopsy is acceptable. Patients without measurable or assessable disease are eligible. - Patients must begin partial brain radiotherapy and temozolomide chemotherapy no sooner than 2 weeks and no later than 5 weeks from the surgery in which tissue was collected. Patients with GBM diagnosis from surgeries in which tissue was not collected will be eligible after repeat surgery performed to collect tissue, as long as no treatment has been initiated prior to surgery in which tissue was collected. In this case, initiation of treatment must begin within 2 to 5 weeks from the last surgery. Patients may have radiotherapy administered at outside facilities according to the specified guidelines (Appendix F). Radiotherapy must be given within 2 days of lapatinib initiation and by external beam to a partial brain field in daily fractions of 2.0 Gy, to a planned total dose to the tumor of 60.0 Gy in accordance with Appendix F. Stereotactic radiosurgery and brachytherapy will not be allowed. - Patients must be willing to forego other drug therapy against the tumor while being treated with pulse dosing of lapatinib and temozolomide and radiation and subsequently pulse dosing lapatinib and temozolomide. - All patients must sign an informed consent approved by the Institutional Review Board indicating that they are aware of the investigational nature of this study. Patients must sign an authorization for the release of their protected health information. - Patients must be > 18 years old, and with a life expectancy > 12 weeks. - Patients must have a Karnofsky performance status of > 60. - Patients must have adequate bone marrow function (WBC > 3,000/µl, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 gm/dl) and the test must be performed within 14 days prior to treatment initiation. Eligibility level for hemoglobin may be reached by transfusion. - Patients must have adequate liver function (AST, ALT < 2.5 times ULN, and bilirubin < 1.5 times ULN) and the test must be performed within 14 days prior to treatment initiation. - Patients must have adequate renal function (creatinine < 1.5 mg/dL) before starting therapy and the test must be performed within 14 days prior to treatment initiation. EXCLUSION CRITERIA - Patients who received previous radiotherapy to the brain. - Patients who received cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy directed against the brain tumor. Patients who received Gliadel wafers will be excluded. Patients may have received or be receiving corticosteroids, analgesics, and other drugs to treat symptoms or prevent complications. - Patients who may be receiving any EIAED (see Appendix C) within 2 weeks prior to registration, or any other prohibited medications within the Washout Period per Appendix D prior to registration. See section 6.5 for seizure medication managements. - Patients with any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy. - Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible. - Women who are pregnant (determined by high titer of serum beta-HCG) or Breast-feeding. (Women with reproductive potential must practice adequate contraception.) - Patients who have any disease that will obscure toxicity or dangerously alter drug metabolism. - Patients who have serious uncontrolled inter-current medical illness including, but not limited to, ongoing or active infection requiring IV antibiotics and psychiatric illness/social situations that would limit compliance with study requirements, or disorders associated with significant immunocompromised state (HIV, SLE, etc.). - Patients who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment). ; PRIMARY OUTCOME: Overall survival; SECONDARY OUTCOME 1:

No

TRIAL NAME: Phase II - Abdominoplasty; BRIEF: Phase 2, single center, randomized, double-blind, placebo-controlled, parallel design study of CA-008 vs. placebo in subjects undergoing an elective C-ABD under general anesthesia supplemented with a bupivacaine hydrochloride (HCl)transverse abdominis plane (TAP) block. ; DRUG USED: CA-008; DRUG CLASS: Non-NME; INDICATION: Postsurgical Pain; TARGET: TRPV1, transient receptor potential vanilloid receptor 1, VR-1; THERAPY: Monotherapy; LEAD SPONSOR: Concentric Analgesics; CRITERIA: Key Inclusion Criteria: - Plan to undergo an elective complete abdominoplasty (C-ABD), without collateral procedure or additional surgeries. - In the medical judgment of the investigator, be a reasonably healthy adult aged 18 - 65 years old, inclusive, and American Society of Anesthesiology (ASA) physical Class 1 or 2 at the time of randomization. - Unless the subject has a same sex partner, he or she must either be sterile (surgically or biologically) or commit to an acceptable method of birth control while participating in the study. - Have a body mass index ≤ 35 kg/m². - Be willing and able to sign the informed consent form (ICF) approved by an Institutional Review Board (IRB). Key Exclusion Criteria: - In the opinion of the Investigator, have a concurrent painful condition that may require analgesic treatment during the study period or may confound post-surgical pain assessments. - Have a known allergy to chili peppers, capsaicin or the components of CA-008, acetaminophen, bupivacaine, fentanyl hydromorphone or oxycodone. - As determined by the investigator have a history or clinical manifestation of significant medical, neuropsychiatric or other condition, including a clinically significant existing arrhythmia, left bundle branch block or abnormal ECG, myocardial infarction or coronary arterial bypass graft surgery within the prior 12 months, significant abnormal clinical laboratory test value, or known bleeding abnormality that could preclude or impair study participation or interfere with study assessments. - The following are considered disallowed medications: 1. Be tolerant to opioids defined as those who have been receiving or have received chronic opioid therapy greater than 15 mg of oral morphine equivalents per day for greater than 3 out of 7 days per week over a one-month period within 6 months of screening. 2. Within 1 day prior to surgery and throughout the inpatient period, be taking any capsaicin-containing products, such as dietary supplements or over-the-counter (OTC) preparations, including topical formulations, and prescription medications. 3. Within the 7 days prior to surgery, be taking any central nervous system (CNS) active agent as an analgesic adjunct medication, such as anticonvulsants, antidepressants, benzodiazepines, sedative- hypnotics, clonidine and other central alpha-2 agents, ketamine or muscle relaxants. i. These drugs are permitted if prescribed for non-pain indications and the dose has been stable for at least 30 days prior to surgery. ii. The use of benzodiazepines and the non-benzodiazepines are permitted to treat insomnia during the postoperative period. ; PRIMARY OUTCOME: Pain Intensity Scores at 96 Hours at Rest Using Numerical Rating Scale (NRS); SECONDARY OUTCOME 1: Weighted Sum of Pain Intensity (SPI) Assessments = AUC of NRS Scores

Yes

TRIAL NAME: Phase II - coBRIM-B (w/Zelboraf); BRIEF: The purpose of this study is to evaluate the effectiveness of the combination of vemurafenib with cobimetinib in patients with active melanoma brain metastases. ; DRUG USED: Cotellic; DRUG CLASS: New Molecular Entity (NME); INDICATION: Melanoma; TARGET: Mitogen-activated ERK kinase (MEK, MAPKK, MAP2K); THERAPY: Combination; LEAD SPONSOR: Melissa Burgess, MD; CRITERIA: Inclusion Criteria: - Signed informed consent - Histologically confirmed metastatic melanoma (Stage IV), carrying BRAF V600-mutation - Melanoma must be documented to contain a BRAFV600 mutation by a CLIA approved laboratory - At least one measurable intracranial target lesion for which all of the following criteria are met: 1. previously untreated or progressive according to RECIST 1.1 (equal to or greater than 20% increase in longest diameter on baseline scan) after previous local therapy (SRS and/or craniotomy) 2. immediate local therapy clinically not indicated or patient is not a suitable candidate to receive immediate local therapy (SRS and/or craniotomy) 3. largest diameter of ≥ 0.5cm but ≤ 4 cm as determined by contrast-enhanced MRI - Prior therapies for extracranial metastatic melanoma including chemo-, cytokine-, immuno-, biological- and vaccine-therapy will be allowed but prior BRAF or MEK not allowed - ECOG PS 0-2 - Life expectancy >12 weeks - Age 18 years or older - Adequate bone marrow function as indicated by the following: 1. ANC > 1500/µL 2. Platelets ≥ 100,000/µL 3. Hemoglobin > 9 g/dL - Adequate renal function, as indicated by creatinine =/< 1.5 x the upper limit of normal (ULN) - Adequate liver function, as indicated by bilirubin =/< 1.5 x ULN - AST or ALT < 3 x ULN (patients with documented liver metastases: AST and/or ALT =/< 5 x ULN) - Able to swallow pills - Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included without serum pregnancy test if they are either surgically sterile or have been postmenopausal for ≥ 1 year - Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician. Effective methods of contraception are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly (for example implants, injectables, combined oral contraception or intra-uterine devices). At the discretion of the Investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) Exclusion Criteria: - Active infection - Prior therapy with BRAFi and/or MEKi - Leptomeningeal disease - Symptomatic brain metastases requiring immediate local interventions such as craniotomy or SRS - Increasing corticosteroid dose in 7 days prior to administration of first dose of study drug. Symptomatic patients that have stable or decreasing corticosteroid use in the past 7 days will be allowed - Current use of therapeutic warfarin - Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI v4.0) [NCI, 2009] Grade 2 or higher from previous anti-cancer therapy, except alopecia - Conditions that will interfere significantly with the absorption of drugs - Inability to undergo MRI secondary to metal, claustrophobia, Gadolinium Contrast allergy - Pregnant, lactating, or breast feeding women - Prior radiation therapy within the last 14 days - Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix - Unwillingness or inability to comply with study and follow-up procedures - The following foods/supplements are prohibited at least 7 days prior to initiation of and during study treatment: 1. St. John's wort or hyperforin 2. Grapefruit juice - History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, Retinal Vein Occlusion (RVO), or neovascular macular degeneration - Uncontrolled glaucoma with intra-ocular pressures > 21mmHg - Serum cholesterol ≥ Grade 2 - Hypertriglyceridemia ≥ Grade 2 - Hyperglycemia (fasting) ≥ Grade 2 - History of clinically significant cardiac dysfunction, including the following: 1. Current unstable angina 2. Current symptomatic congestive heart failure of NYHA class 2 or higher 3. History of congenital long QT syndrome or mean QTcF > 450 msec at baseline or uncorrectable electrolyte abnormalities 4. Uncontrolled hypertension ≥ Grade 2 (patients with a history hypertension controlled with anti-hypertensives to ≤ Grade 1 are eligible) 5. Left ventricular ejection fraction (LVEF) below 50% 6. Uncontrolled Arrhythmias 7. Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack within the previous 6 months ; PRIMARY OUTCOME: Objective Intracranial Response (OIRR); SECONDARY OUTCOME 1: Overall Response

No

TRIAL NAME: Phase III - vs. Linezolid; BRIEF: This study will be a double-blind, randomized, multicenter trial to assess the safety and efficacy of a single 1500 mg IV dose of dalbavancin plus a single 500 mg IV dose of azithromycin in comparison to an approved antibiotic regimen of linezolid 600 mg every 12 hours for 10-14 days plus a single 500 mg IV dose of azithromycin for the treatment of Community Acquired Bacterial Pneumonia. ; DRUG USED: Dalvance; DRUG CLASS: New Molecular Entity (NME); INDICATION: Community Acquired Pneumonia (CAP) (Antibacterial); TARGET: Cell wall synthesis; THERAPY: Monotherapy; LEAD SPONSOR: Durata Therapeutics Inc., an affiliate of Allergan plc; CRITERIA: Inclusion Criteria: 1. Adults aged 18 to 85, inclusive 2. Has given written, informed consent 3. Has acute illness with onset within previous 7 days 4. Has at least 2 of the following symptoms: - Difficulty breathing or shortness of breath - Cough - Production of purulent sputum - Pleuritic chest pain 5. Has at least 2 vital sign abnormalities: - Fever (> 38°C or < 35°C) - Hypotension (systolic BP < 90 mm Hg) - Tachycardia (> 100 beats /min) - Tachypnea (> 24 breaths /min) 6. Has at least one other clinical or laboratory abnormalities: - Hypoxemia (room air SaO2 < 90% ) - Clinical evidence of pulmonary consolidation - Elevated WBC count or neutropenia (> 12,000/mm3 or < 4,000/mm3) 7. Has new lobar or multi-lobar infiltrates on chest radiograph 8. Has CURB-65 risk category 1 to 4. Patients with CURB-65 risk category 1 will be limited to 20% of the total patient population Exclusion Criteria: 1. Contra-indication to the administration of any of the study treatments, such as hypersensitivity to any of the glycopeptide agents, beta-lactam agents, linezolid or macrolide antibiotics, or current or recent (within 2 weeks) use of MAO inhibitors or serotonergic antidepressants (within 5 weeks for fluoxetine) (see Section 5.5.1) 2. Has received antibiotic therapy in the 4 days prior to screening, with the following exception: up to 25% of patients may have received a single dose of a short acting (half life < 8 hours) antibiotic 3. Has aspiration pneumonia 4. Has hospital acquired or ventilator associated pneumonia, or healthcare associated pneumonia, or 2 or more days in hospital in the previous 90 days 5. Has cystic fibrosis or known or suspected Pneumocystis pneumonia or known or suspected active tuberculosis 6. Females of child-bearing potential who are unable to take adequate contraceptive precautions, have a positive pregnancy result within 24 hours prior to study entry, are known to be pregnant, or are currently breastfeeding an infant 7. Has primary or metastatic lung cancer 8. Has known bronchial obstruction or a history of post-obstructive pneumonia 9. Requires admission to ICU at baseline 10. Has empyema requiring drainage 11. Infection due to an organism known prior to study entry to be resistant to either treatment regimen 12. Has known or suspected infection due solely to an atypical pathogen such as Mycoplasma sp., Chlamydia sp. or Legionella sp. or positive Legionella urinary antigen at baseline 13. Absolute neutrophil count < 500 cells/mm3 14. Known or suspected human immunodeficiency virus (HIV) infected patients with a CD4 cell count < 200 cells/mm3 or with a past or current acquired immunodeficiency syndrome (AIDS)-defining condition and unknown CD4 count 15. Patients with a recent bone marrow transplant (in post-transplant hospital stay) 16. Patients receiving oral steroids > 40 mg prednisolone per day (or equivalent) or receiving immunosuppressant drugs after organ transplantation 17. Patients with a rapidly fatal illness, who are not expected to survive for 3 months 18. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study 19. Has participated in another trial of an investigational pharmaceutical product in the 30 days prior to enrollment 20. Prior participation in this trial. ; PRIMARY OUTCOME: Treatment Response of CABP Symptoms; SECONDARY OUTCOME 1: Efficacy of dalbavancin to the comparator regimen

No

TRIAL NAME: Phase II - BAYOU (w/Olaparib, First-Line); BRIEF: A Phase II, Randomized, Multi-Center, Double-Blind, Comparative Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With Olaparib for First-Line Treatment in Platinum-Ineligible Patients With Unresectable Stage IV Urothelial Cancer ; DRUG USED: Imfinzi; DRUG CLASS: Biologic; INDICATION: Bladder Cancer; TARGET: Immune System, Programmed death-1 receptor (PD-1) / Programmed death ligands (PD-L1 and PD-L2); THERAPY: Combination; LEAD SPONSOR: AstraZeneca; CRITERIA: Inclusion criteria: 1. Provision of signed and dated, written ICF 2. Histologically or cytologically documented TCC/UC of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra) also meeting the following: Unresectable, Stage IV disease; No prior systemic therapy for unresectable, Stage IV disease. 3. Ineligible for platinum-based chemotherapy defined as (i) in the opinion of the Investigator, unfit for carboplatin-based chemotherapy and (ii) meeting one of the following criteria: CrCl <60 mL/min calculated by Cockcroft-Gault equation; Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 audiometric hearing loss (25 dB in 2 consecutive wave ranges); CTCAE Grade ≥2 peripheral neuropathy; New York Heart Association Class III heart failure; ECOG 2. 4. Known tumor HRR mutation status prior to randomization. 5. World Health Organization (WHO)/ECOG performance status of 0, 1, or 2. 6. Patients with at least 1 RECIST 1.1 target lesion at baseline. 7. Ability to swallow oral medications. 8. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients. Exclusion criteria 1. Active or prior documented autoimmune or inflammatory disorders. 2. Other invasive malignancy within 5 years before the first dose of the IP. 3. Major surgical procedure within 28 days prior to the first dose 4. Brain metastases or spinal cord compression unless the patient's condition is stable and off steroid for at least 14 days 5. History of active primary immunodeficiency. 6. Active infection including tuberculosis (TB) 7. History of allogenic organ transplantation. 8. Uncontrolled intercurrent illness 9. Prior exposure to a PARP inhibitor or immune-mediated therapy. 10. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. 11. Current or prior use of immunosuppressive medication within 14 days before the first dose of the IP. 12. No radiation therapy is allowed, unless it is (1) definitive radiation that had been administered at least 12 months prior; (2) palliative radiation to the brain, with associated criteria for stability or lack of symptoms; or (3) palliative radiation to painful bony lesions (this must comprise less than 30% of the bone marrow) or symptomatic pelvic soft tissue mass(es). 13. Receipt of live attenuated vaccine within 30 days prior to the first dose of the IP. 14. Patients with a known hypersensitivity to durvalumab, olaparib, or any of the excipients of the products. 15. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab and 6 months for participants taking also Olaparib in case of female participants, 90 days after receipt of the last dose of the IP in case of male participants. ; PRIMARY OUTCOME: Progression-free Survival (PFS); SECONDARY OUTCOME 1: Overall Survival (OS)

No

TRIAL NAME: Phase II - EXPECT (T-cell NHL) (TCL-001); BRIEF: This is a Phase II, multicenter, single-arm, open-label study of oral lenalidomide monotherapy administered to subjects with relapsed or refractory T-cell lymphoma. This study will be conducted in two phases: a Treatment Phase and a Follow-up Phase. Subjects who qualify for enrollment into the study will enter the Treatment Phase and receive single-agent lenalidomide 25 mg once daily on Days 1-21 every 28 days (28-day cycles). Subjects may continue participation in the Treatment Phase of the study for a maximum duration of 24 months, or until disease progression or unacceptable adverse events develop. All subjects who discontinue the Treatment Phase for any reason will continue to be followed until progression of disease or until next lymphoma treatment is given, whichever comes first, during the Follow-up Phase. Objectives: Primary: • To determine the efficacy of lenalidomide monotherapy in relapsed or refractory T-cell Non-Hodgkin's Lymphoma (NHL). Efficacy will be assessed by measuring the response rate, tumor control rate, duration of response, time to progression and progression free survival. Secondary: • To evaluate the safety of lenalidomide monotherapy as treatment for subjects with relapsed or refractory T-cell NHL. ; DRUG USED: Revlimid; DRUG CLASS: New Molecular Entity (NME); INDICATION: Cutaneous T-Cell Lymphoma (CTCL) - NHL; TARGET: Angiogenesis, E3 ubiquitin ligase, Immune System; THERAPY: Monotherapy; LEAD SPONSOR: Celgene; CRITERIA: Inclusion Criteria: - Must understand and voluntarily sign an informed consent form. - Must be ≥ 18 years of age at the time of signing the informed consent form. - Must be able to adhere to the study visit schedule and other protocol requirements. - Biopsy-proven T-cell Non-Hodgkin's Lymphoma, either: - Peripheral T-cell Lymphoma (PTCL) whatever the subtype, or - Cutaneous T-cell Lymphoma (CTCL), but only the subtype mycosis fungoides. - Relapsed or refractory to previous therapy for T-cell Non-Hodgkin's Lymphoma. - Must have received at least one prior combination chemotherapy regimen. There is no limit on the number of prior therapies. Exclusion Criteria: - Cutaneous T-cell Lymphoma of subtype Sézary Syndrome. ; PRIMARY OUTCOME: Participants Categorized by Best Response as Determined by Investigator; SECONDARY OUTCOME 1: Duration of Response

No

TRIAL NAME: Phase III - TELECAST (Companion Study to TELESTAR; Carcinoid Syndrome); BRIEF: The purpose of the study is to evaluate the effect of telotristat etiprate versus placebo on the incidence of treatment-emergent adverse events and on 5-hydroxyindoleacetic acid (5-HIAA) levels. ; DRUG USED: Xermelo; DRUG CLASS: New Molecular Entity (NME); INDICATION: Neuroendocrine Tumors (NET); TARGET: Tryptophan hydroxylase; THERAPY: Monotherapy; LEAD SPONSOR: Lexicon Pharmaceuticals; CRITERIA: Inclusion Criteria: - Patients ≥ 18 years of age - All patients of reproductive potential must agree to use an adequate method of contraception during the study and for 12 weeks after the Follow-up visit. - Histopathologically-confirmed, well-differentiated metastatic neuroendocrine tumor - Documented history of carcinoid syndrome - Patient is able and willing to provide written informed consent prior to participation Exclusion Criteria: - Presence of diarrhea attributed to any condition other than carcinoid syndrome. - Presence of 12 or more watery bowel movements per day - Positive stool examination for enteric pathogens, pathogenic ova or parasites, of Clostridium difficile at Screening - Karnofsky Performance Status ≤ 60% - Presence of any clinically significant laboratory, medical history, or physical examination findings deemed unacceptable by the Investigator - A history of short bowel syndrome - History of constipation within 2 years of Screening - Life expectancy < 12 months from Screening ; PRIMARY OUTCOME: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Treatment Period; SECONDARY OUTCOME 1: Change From Baseline in the Number of Bowel Movements (BMs) Per Day Averaged Over 12 Weeks

Yes

TRIAL NAME: Phase I/II - Epithelial Cancer; BRIEF: The primary objective in Phase I is to evaluate the safety and tolerability of sacituzumab govitecan-hziy (SG) as a single agent administered in 21-day treatment cycles in previously treated participants with advanced epithelial cancer. In Phase II, the primary objective is to evaluate the safety and efficacy of sacituzumab govitecan-hziy administered in 21-day treatment cycles at a dose selected in Phase I. Tumor types in the study will include: cervical, colorectal, endometrial, ovarian, esophageal, gastric adenocarcinoma, glioblastoma multiforme, head and neck cancers- squamous cell, hepatocellular, prostate, non-small-cell lung cancer, pancreatic, renal cell, small-cell lung cancer, non-triple negative breast cancer (non-TNBC), triple-negative breast cancer (TNBC) and metastatic urothelial cancer (mUC). ; DRUG USED: Trodelvy; DRUG CLASS: Biologic; INDICATION: Non-Small Cell Lung Cancer (NSCLC); TARGET: Antibody-drug Conjugate (ADC), Trop-2; THERAPY: Monotherapy; LEAD SPONSOR: Gilead Sciences; CRITERIA: Inclusion Criteria: - Individuals able to understand and give written informed consent. - Histologically or cytologically confirmed epithelial cancer of one of the following types: - Gastric adenocarcinoma (GC) - Esophageal cancer (EC) - Hepatocellular carcinoma (HCC) - Non-small-cell lung cancer (NSCLC) - Small-cell lung cancer (SCLC) - Epithelial ovarian cancer (EOC) - Cervical Cancer - Endometrial Cancer - Triple-negative breast cancer (TNBC) - Non-triple-negative breast cancer - Papillary thyroid cancer (excludes follicular, medullary, Hurthle cell, and anaplastic thyroid cancer) - Glioblastoma multiforme (GBM) - Hormone-refractory prostate cancer (HRPC) - Head and neck cancers- squamous cell (SCCHN) - Renal cell cancer (clear cell) (RCC) - Urothelial cancer - Stage IV (metastatic) disease (except for individuals with GBM). - Refractory to or relapsed after at least one prior standard therapeutic regimen - Adequate performance status (ECOG 0 or 1) - Expected survival ≥ 6 months. - Measurable disease by CT or MRI. - At least 2 weeks beyond treatment (chemotherapy, investigational drugs including small molecular inhibitors, immunotherapy and/or radiation therapy) or major surgery and recovered from all acute toxicities to Grade 1 or less (except alopecia). - At least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids < 20 mg prednisone or equivalent daily are permitted). - Adequate hematology without ongoing transfusional support (hemoglobin > 9 g/dL, absolute neutrophil count (ANC) > 1,500 per mm^3, platelets > 100,000 per mm^3). - Adequate renal and hepatic function (creatinine ≤ 2.0 x institutional upper limit of normal (IULN), bilirubin ≤ 1.5 IULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x IULN or 5 x IULN if know liver metastases). - Otherwise, all toxicity at study entry ≤ Grade 1. Exclusion Criteria: - Women who are pregnant or lactating. - Women of childbearing potential and fertile men unwilling to use effective contraception during study until conclusion of 12-week post-treatment evaluation period. - Individuals with Gilbert's disease. - Individuals with brain metastases can be enrolled only if treated, non-progressive brain metastases and off high-dose steroids (> 20 mg prednisone or equivalent) for at least 4 weeks. - Presence of bulky disease (defined as any single mass > 7 cm in its greatest dimension). Individuals with a mass over 7 cm, but otherwise eligible, may be considered for enrollment after discussion and approval with the medical monitor. - Individuals with active ≥ grade 2 anorexia, nausea or vomiting, and/or signs of intestinal obstruction. - Individuals with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while individuals with other prior malignancies must have had at least a 3-year disease-free interval. - Individuals known to be HIV positive, hepatitis B positive, or hepatitis C positive. - Known history of unstable angina, MI, or CHF present within 6 months or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy. - Known history of clinically significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months. - Prior history of clinically significant bleeding, intestinal obstruction, or GI perforation within 6 months of initiation of study treatment. - Infection requiring intravenous antibiotic use within 1 week. - History of an anaphylactic reaction to irinotecan or ≥ Grade 3 GI toxicity to prior irinotecan, - Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations. ; PRIMARY OUTCOME: Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events; SECONDARY OUTCOME 1: Duration of Response by ICR

Yes

TRIAL NAME: Phase I - Healthy Volunteers; BRIEF: The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK) and immunogenicity of JNJ-61178104 following a single ascending Intravenous (IV) dose administration and a single Subcutaneous (SC) dose administration in healthy participants. ; DRUG USED: JNJ-61178104; DRUG CLASS: Biologic; INDICATION: Autoimmune Disorders; TARGET: Unknown; THERAPY: Monotherapy; LEAD SPONSOR: Janssen Research & Development, LLC; CRITERIA: Inclusion Criteria - Participant must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study - Participant must have a body weight in the range of 50 Kilogram (kg) to 100 kg, inclusive, and have a body mass index of 19 Kilogram per meter square (kg/m^2) to 30 kg/m2, inclusive - Participant must be healthy on the basis of clinical laboratory tests performed at Screening and Day-1. If the results of the serum chemistry panel including liver enzymes, hematology panel, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's medical record with documented review confirmation by the investigator - Before randomization, a woman must not be of childbearing potential: a) Postmenopausal {greater than (>) 45 years of age with amenorrhea for at least 12 months or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) level >40 International Units Per Litre (IU/L) at Screening}; or b) Permanently sterilized (example, bilateral tubal occlusion, hysterectomy, bilateral salpingectomy, oophorectomy); or c) Otherwise be incapable of pregnancy - Be considered eligible according to the following tuberculosis (TB) Screening criteria: a) Have no history of latent or active TB prior to Screening; b) Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination; c) Have had no recent close contact with a person with active TB; d) Have a negative T-Spot TB test result at Screening Exclusion Criteria: - Participant currently has or has a history of any clinically significant medical illness or medical disorders the investigator considers should exclude the participant, including (but not limited to), neuromuscular, hematological disease, immune deficiency state, cardiac, vascular, metabolic, endocrine, rheumatologic, respiratory disease, hepatic or gastrointestinal disease, neurological or psychiatric disease, ophthalmological disorders, neoplastic disease, renal or urinary tract diseases, or dermatological disease - Participant has a QT corrected according to Fridericia's formula (QTcF) interval >450 msec, has a complete left or right bundle branch block, or has a history or current evidence of additional risk factors for torsades de pointes (example, heart failure, hypokalemia, family history of Long QT Syndrome) at Screening and at Day -1 - Participant has had major surgery, (example, requiring general anesthesia) within 4 months before Screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study or within 17 weeks after the last dose of study drug administration - Participant plans to undergo non-major elective surgery within 4 weeks prior to study drug administration through the end of the study - Participant has a known or suspected intolerance or hypersensitivity to any biologic medication or known allergies or clinically significant reactions to murine, chimeric, or human proteins, monoclonal antibodies or antibody fragments, or to any components of the formulation of JNJ-61178104 and its excipients used in this study ; PRIMARY OUTCOME: Number of Participants With Adverse Events Following Study Drug Administration as a Measure of Safety and Tolerability; SECONDARY OUTCOME 1: Serum Concentration of JNJ-61178104

No

TRIAL NAME: Phase I - Single Dose Escalation; BRIEF: The primary purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of GSK3050002 in humans. Subjects will attend the clinical unit for a screening visit and if eligible and consenting, will attend to participate in the study within 30 days. Subjects will be admitted to the clinical unit the evening prior to dosing when each subject will receive a single intravenous dose of GSK3050002 or placebo, then remain in house under supervision until discharged on Day 3. Subjects will then return for 7 outpatient visits scheduled over the following 81 days. Finally, the follow-up visit will be 7-14 days following the last visit. ; DRUG USED: GSK3050002; DRUG CLASS: Biologic; INDICATION: Psoriatic Arthritis (PA); TARGET: Chemokine (C-C motif) ligand 20 (CCL20); THERAPY: Monotherapy; LEAD SPONSOR: GlaxoSmithKline; CRITERIA: Inclusion Criteria: - Male aged between 18 and 65 years of age inclusive, at the time of signing the informed consent. - Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and 12- lead ECG. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria may be included only if the Investigator in consultation with the GSK Medical Monitor [if required] agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. - Body mass index (BMI) within the range 18 - 29 kilogram per meter square [kg/m^2] (inclusive). - Male subjects with female partners of child-bearing potential must agree to use one of the listed contraception methods. This criterion must be followed for 1 month prior to the first dose of study medication for 15 weeks post dose. - Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. - Suitable for cannulation and with adequate venous access. - Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <= 1.5xUpper limit of Normal [ULN] (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). - Based on a single ECG QTcF < 450 milliseconds (msec). Exclusion Criteria: - Criteria Based Upon Medical Histories - Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). - History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >21 units. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits. - History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. - History of severe drug allergies including type 1 hypersensitivity reaction to parental administration of contrast agents, human or murine proteins or monoclonal antibodies. - Subject has acne which requires prescription treatment - Criteria Based Upon Diagnostic Assessments - A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening - A positive pre-study drug/alcohol screen. - A positive test for Human immunodeficiency virus (HIV) antibody. - Subject is a heavy smoker as defined by a positive smoking breath test of >10 parts per million (ppm) carbon monoxide (CO). - Other Criteria - Evidence of current or at risk of developing bacterial, fungal, or viral infection at screening or within 7 days before dosing. - Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. - The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). - Subject is unable to refrain from taking prescription or non-prescription drugs (including vitamins and dietary or herbal supplements), within 7 days prior to the first dose of study medication until completion of the follow-up visit, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study. - Subject is unable to abstain from travelling to area which carry a high risk of infection for the duration of the study. - Exposure to more than four new chemical entities within 12 months prior to the first dosing day. - Subject is unable to abstain from being vaccinated or immunized for 4 weeks prior to dosing and for 19 weeks after the study. ; PRIMARY OUTCOME: Number of subjects with adverse events; SECONDARY OUTCOME 1: Chemokine (C-C motif) ligand 20 (CCL20) levels in blood

No

TRIAL NAME: Phase I - w/Vemurafenib (NCI, 1st Line); BRIEF: Background: - One possible treatment for advanced melanoma involves collecting white blood cells from the person with cancer and growing them in a laboratory. The cells can then be given back to the donor. This study will use this white blood cell treatment with the cancer treatment drug vemurafenib. Vemurafenib targets melanoma cells that have a mutation in the B-raf gene, and may be able to make them shrink. Objectives: - To see if vemurafenib and white blood cell therapy is a safe and effective treatment for advanced melanoma. Eligibility: - Individuals at least 18 years and less than or equal to 66 years of age who have advanced melanoma that contains the B-raf genetic mutation. Design: - Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. - White blood cells will be collected from tumor cells. These cells will be collected during surgery or a tumor biopsy. - Participants will have leukapheresis to collect additional white blood cells for the procedure. - Participants will take vemurafenib twice a day, starting 3 weeks before receiving the white blood cells. - Participants will have 1 week of chemotherapy to prepare their immune system to accept the white blood cells. - Participants will receive an infusion of their collected white blood cells. They will also receive aldesleukin for up to 5 days to boost the immune system s response to the white blood cells. They will remain in the hospital until they have recovered from the treatment. - Participants will have frequent follow-up visits to monitor the outcome of the treatment. ; DRUG USED: LN-144; DRUG CLASS: Biologic; INDICATION: Melanoma; TARGET: Immune System, Stem Cells/Other Cell Therapies, T lymphocytes; THERAPY: Combination; LEAD SPONSOR: National Cancer Institute (NCI); CRITERIA: -INCLUSION CRITERIA: 1. Measurable metastatic melanoma that expresses the VtoE BRAF mutation and VtoK BRAF mutation assessed in a CLIA certified laboratory. 2. Patients with 3 or less brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible. 3. Greater than or equal to 18 and less than or equal to 66 years of age. 4. Patients of both genders must be willing to practice birth control from the time of enrollment on the study and for four months after treatment. 5. Life expectancy of greater than three months 6. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus. 7. Willing to sign a durable power of attorney. 8. Able to understand and sign the Informed Consent Document 9. Clinical performance status of ECOG 0 or 1. 10. Hematology: - Absolute neutrophil count greater than 1000/mm(3) - Hemoglobin greater than 8.0 g/dl - Platelet count greater than 100,000/mm(3) 11. Serology: - Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.) - Seronegative for hepatitis B antigen, or hepatitis C antibody or antigen. 12. Chemistry: - Serum ALT/AST less than three times the upper limit of normal. - Calculated creatinine clearance (eGFR) > 50 ml/min. - Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert s Syndrome who must have a total bilirubin less than 3 mg/dl. 13. More than four weeks must have elapsed since any prior systemic therapy at the time of treatment, and patients toxicities must have recovered to a grade 1 or less (except for alopecia or vitiligo). Patients must have stable or progressing disease after prior treatment. Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria in Section 2.1.1. 14. Six weeks must have elapsed from the time of any antibody therapy that could affect an anti cancer immune response, including anti-CTLA4 antibody therapy at the time the patient receives the preparative regimen to allow antibody levels to decline. Note: Patients who have previously received ipilimumab and have documented GI toxicity must have a normal colonoscopy with normal colonic biopsies. 15. EKG with mean QTc interval < 450 msec. EXCLUSION CRITERIA: 1. Prior cell transfer therapy which included a myeloablative chemotherapy regimen (i.e. 1200 TBI or 200 TBI plus chemotherapy). 2. Previous treatment with Vemurafenib. 3. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant. 4. Systemic steroid therapy requirement. 5. Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease. 6. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS). 7. Opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.) 8. History of severe immediate hypersensitivity reaction to any of the agents used in this study. 9. History of coronary revascularization or ischemic symptoms. 10. Any patient known to have an LVEF less than or equal to 45 percent. 11. In patients > 60 years old, documented LVEF of less than or equal to 45 percent. ; PRIMARY OUTCOME: Determine the safety of the administration of vemurafenib in conjunction with ACT consisting of autologous TIL infused along with high dose aldesleukin following a non-myeloablative lymphodepleting preparative regimen.; SECONDARY OUTCOME 1:

No

TRIAL NAME: Phase Ib - Healthy Volunteers; BRIEF: This is a single-center, randomized, double-blind, placebo-controlled, ascending, single-infusion, sequential group study. Single, ascending doses will be administered to approximately 64 subjects, with an option for 1 additional multi-dose cohort in approximately 8 subjects. The primary objective is to evaluate the safety of ANX005 administered as an intravenous infusion as a single agent and in combination with intravenous immunoglobulin (IVIg). The optional multi-dose cohort will evaluate either additional subjects at the maximum tolerated dose or ANX005 administered as 2 infusions. ; DRUG USED: ANX-005; DRUG CLASS: Biologic; INDICATION: Guillain-Barré Syndrome; TARGET: Complement Component 1q (C1q), Complement Pathway; THERAPY: Monotherapy and Combo Therapy; LEAD SPONSOR: Annexon, Inc.; CRITERIA: Inclusion Criteria: - Male and females 18 years and older - Females must be postmenopausal, surgically sterilized, or willing and able to use 2 methods of contraception throughout the study and for 1 month after the final study visit - Willing and able to undergo vaccination if not vaccinated recently Exclusion Criteria: - History of any autoimmune disease, meningitis, septicemia or pneumonia - History of hypercoagulable diseases, hyperviscosity, thrombosis, renal dysfunction or acute renal failure - Known genetic deficiencies of the complement cascade system - History of conditions whose symptoms and effects could alter protein catabolism or IgG utilization, e.g. protein-losing enteropathies or nephrotic syndrome - Body weight less than 50 kg or greater than 100 kg - Hypersensitivity or allergic reactions to any excipients in the ANX005 drug product - (Cohorts 4b and 5b) Known selective IgA deficiency or presence of antibodies to IgA at screening - (Cohorts 4b and 5b) Prior reaction or hypersensitivity to blood products, including IVIg or any of the excipients in IVIg. ; PRIMARY OUTCOME: Number of subjects with treatment-related adverse events as assessed by CTCAE v4.03; SECONDARY OUTCOME 1: Peak plasma concentration

No

TRIAL NAME: Phase III - DR-ADV-301 (Military Personnel); BRIEF: This is a multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of oral DR-5001 in reducing the attack rate of febrile acute respiratory disease caused by type-4 and type-7 adenovirus as well as determine its immunogenicity. ; DRUG USED: Adenovirus Type 4 and Type 7 Vaccine, Live; DRUG CLASS: Vaccine; INDICATION: Antiviral - Miscellaneous Vaccines; TARGET: DNA polymerase; THERAPY: Monotherapy; LEAD SPONSOR: Duramed Research; CRITERIA: Inclusion Criteria: - Military recruit in training - Male or female; if female, must be of non-childbearing potential or with a documented negative pregnancy test </= 72 hours prior to study medication administration and agree not to become pregnant Exclusion Criteria: - Female nursing an infant or planning on nursing during the study - Immunosuppressed for any reason, including past (within last 6 months) or current treatment with immunosuppressive therapy - Known allergy to any component of the vaccines and/or placebo tablets - Immunocompromised sexual partner or immunocompromised individuals in home ; PRIMARY OUTCOME: Number of Participants With Wild Type-4 Febrile Adenovirus (ADV) Acute Respiratory Disease (ARD) -- ITT Cohort; SECONDARY OUTCOME 1: Percentage of Participants Showing ADV-4 Seroconversion at Week 4

Yes

TRIAL NAME: Phase III - A0081251 (Safety Extension); BRIEF: This study examines the safety of pregabalin over a 6 month period in patients with neuropathic pain associated with HIV infection as an extension of another trial that tests the efficacy of pregabalin. ; DRUG USED: Lyrica; DRUG CLASS: New Molecular Entity (NME); INDICATION: HIV-Associated Distal Sensory Polyneuropathy (HIV-DSP); TARGET: Voltage-gated calcium channels; THERAPY: Monotherapy; LEAD SPONSOR: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.; CRITERIA: Inclusion Criteria: - Subjects who participated in the preceding A0081244 double-blind trial and completed at least through Visit 9 of that trial. Subjects with painful distal sensory polyneuropathy (DSP) interested in treatment based on investigator's clinical judgment. Subjects who had acceptable tolerability of study drug in A0081244. Exclusion Criteria: - Clinically significant or unstable conditions that, in the opinion of the investigator, would compromise participation in the study. This includes, for example, medical conditions such as, but not limited to: hepatic, renal, respiratory, hematological, immunological, cardiovascular diseases, arrhythmia, inflammatory or rheumatologic disease, active infections, symptomatic peripheral vascular disease, psychiatric illness, and untreated endocrine disorders. - Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. - Active Acquired Immune Deficiency Syndrome (AIDS)- defining Opportunistic Infection (OI) that requires hospitalization. ; PRIMARY OUTCOME: Number of Participants With Treatment Emergent (TE) Adverse Events (AEs) and Serious Adverse Events (SAEs); SECONDARY OUTCOME 1: Number of Participants Who Were Employed or Unemployed Assessed by Work Productivity and Activity Impairment: Specific Health Problem (WPAI: SHP) Questionnaire

No

TRIAL NAME: Phase III - ARCADE (Low Risk MDS); BRIEF: The primary objective was to assess the superiority of darbepoetin alfa versus placebo on the incidence of red blood cell transfusions during the 24-week double-blind treatment period in anemic patients with low or intermediate-1 risk MDS. ; DRUG USED: Aranesp; DRUG CLASS: Biologic; INDICATION: Myelodysplastic Syndrome (MDS); TARGET: Erythropoietin Receptor (EPOR); THERAPY: Monotherapy; LEAD SPONSOR: Amgen; CRITERIA: Inclusion Criteria: - Low or intermediate-1 risk MDS patients per International Prognostic Scoring System (IPSS) at the time of randomisation, as determined by complete blood count (CBC) during screening and bone marrow examination and marrow cytogenetic analysis performed within 16 weeks prior to randomisation. Subject cannot have been rendered low or intermediate-1 risk by prior disease modifying therapy. Bone marrow slides must be available for centralized review at any time throughout the study - World Health Organization (WHO) classification of refractory anemia (RA), refractory anemia with ring sideroblasts (RARS), refractory cytopenias with multilineage dysplasia (RCMD), MDS-unclassified (MDSU), MDS with isolated del(5q) (5q- syndrome) or refractory anaemia with excess blasts-1 (RAEB-1) - Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 assessed during screening - Haemoglobin level ≤ 10.0 g/dL as assessed by the local laboratory; sample obtained within 7 days prior to randomisation (retest during screening is acceptable) - Adequate transferrin saturation (Tsat) (≥ 15%) and serum ferritin (≥ 10 ng/mL) as assessed by the central laboratory during screening (supplementation and retest during screening is acceptable) - Adequate serum folate (≥ 4.5 nmol/L [≥ 2.0 ng/mL]) or RBC folate (≥ 317 nmol/L [≥ 140 ng/mL]) as assessed by the local laboratory during screening (supplementation and retest during screening is acceptable) - Adequate vitamin B12 (≥ 148 pmol/L [≥ 200 pg/mL]) as assessed by the local laboratory during screening (supplementation and retest during screening is acceptable) - 18 years of age or older - Subject or subject's legally acceptable representative has provided informed consent - Exclusion Criteria: - Previously diagnosed with intermediate-2 or high risk MDS per IPSS - Therapy-related or secondary MDS - History of acute leukemia - Evidence of bone marrow collagen fibrosis - Inherited anaemia (eg, haemoglobinopathy, thalassemia, red cell membrane defect, red cell enzyme deficiency), active hemorrhage, red cell aplasia, haemolytic anaemia - History of malignancies other than curatively treated non-melanoma skin or in situ carcinoma - History of thrombosis within 6 months prior to randomisation - Previous bone marrow or stem cell transplantation - Uncontrolled angina, uncontrolled heart failure, or uncontrolled cardiac arrhythmia as determined by the investigator at screening. Subjects with known myocardial infarction within 6 months prior to randomisation - Uncontrolled hypertension defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg at screening - Clinically significant systemic infection or uncontrolled chronic inflammatory disease (ie, rheumatoid arthritis, inflammatory bowel disease) as determined by the investigator at screening - History of seizure disorder (subject with previous history of seizure disorder will be eligible for the study if he/she had no evidence of seizure activity within 5 years of randomisation and is currently free of antiseizure medication) - Previous or ongoing use of erythropoiesis-stimulating agent (ESA) therapy, eg, recombinant human erythropoietin (rHuEpo), darbepoetin alfa - High transfusion demand: receiving a total of ≥ 4 units of RBC transfusion during either of 2 consecutive 8-week periods (ie, days -113 to -57 or days -56 to 0) prior to randomisation - Received any RBC transfusion within 14 days prior to randomisation - Received cytotoxic chemotherapy for any oncologic indication or planning to receive cytotoxic chemotherapy during the double-blind treatment period of the study - Received biologic response modifiers (eg, thalidomide, lenalidomide, arsenic trioxide, azacitidine, decitabine) to treat MDS or planning to receive biologic response modifiers during the double-blind treatment period of the study - Received myeloablative or craniospinal radiation or planning to receive myeloablative or craniospinal radiation during the double-blind treatment period of the study - Received granulocyte colony stimulating factor (G-CSF) therapy within 30 days prior to randomization or planning to receive G-CSF therapy during the double-blind treatment period of the study (temporary use of G-CSF for neutropenia with fever and/or infection is acceptable) - Abnormal renal function (serum creatinine level > 2 times the upper limit of the respective normal range [ULN]) as assessed by the central laboratory at screening - Abnormal liver function (total bilirubin > 2 times, alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 3 times ULN) as assessed by the central laboratory at screening. (Subjects with abnormal bilirubin at screening due to documented Gilbert's Disease are eligible if all other criteria are met.) - Serum endogenous erythropoetin (EPO) level > 500 mU/mL as assessed by the central laboratory at screening - Known seropositivity for human immunodeficiency virus (HIV) or diagnosis of acquired Immunodeficiency syndrome (AIDS), positive for hepatitis B surface antigen, or seropositive for hepatitis C virus - Subjects with active ethanol abuse, as judged by the investigator - Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s) - Female subject is not willing to use highly effective contraception during treatment and for at least 1 month after the end of treatment - Female subject is pregnant or planning to become pregnant within 1 month after the end of treatment - Subject has known sensitivity to any of the products to be administered during dosing - Subject has previously been randomised into this study - Subject will not be available for protocol-required study visits, to the best of the subject and investigator's knowledge - Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures - Confirmed history of neutralising antibody activity to rHuEpo or darbepoetin alfa ; PRIMARY OUTCOME: Percentage of Participants With at Least One Red Blood Cell (RBC) Transfusion During the Double-blind Treatment Period; SECONDARY OUTCOME 1: Percentage of Participants Who Achieved an Erythroid Response Based on International Working Group (IWG) 2006 Criteria in the Double-blind Treatment Period

No

TRIAL NAME: Phase I/II - w/Gemcitabine; BRIEF: The purpose of this study is to evaluate the safety and tolerability of selected dose 1.2mg/kg BID dosage administered subcutaneously (SC) administered PCI-27483 to metastatic or locally advanced pancreatic cancer patients receiving concurrent therapy with intravenously administered gemcitabine for 12 weeks. ; DRUG USED: PCI-27483; DRUG CLASS: New Molecular Entity (NME); INDICATION: Pancreatic Cancer; TARGET: Coagulation Factor VII; THERAPY: Combination; LEAD SPONSOR: Pharmacyclics LLC.; CRITERIA: Inclusion Criteria: 1. Men or women at least 18 years old 2. Body weight ≥ 40 and ≤ 100 kg. 3. Part A: Metastatic ductal adenocarcinoma of the pancreas diagnosed ≤ 4 months prior to enrollment. (Locally advanced does not have any criteria) 4. Part B: Locally advanced ductal adenocarcinoma of the pancreas diagnosed ≤ 3 months prior to enrollment or metastatic ductal adenocarcinoma diagnosed ≤ 2 months. 5. Measurable disease by spiral CT scan (SCT) in accordance with RECIST criteria. 6. Patients after non-curative surgery are eligible if at least 4 weeks after surgery and recovered from significant surgical morbidity. 7. Estimated life expectancy of at least 4 months. 8. ECOG performance status 0 to 1. 9. Normal baseline coagulation function as defined by: 1. PT 10-16 seconds, and 2. aPTT 22-38 seconds. 10. Agree to not participate in contact sports or strenuous activity while taking PCI-27483. 11. Ability to understand the study, willingness to participate in the study for the study duration, and ability to provide written informed consent to participate. Exclusion Criteria: 1. History of any clinically significant medical condition that, in the opinion of the Principal Investigator, would interfere with the study evaluation or interpretation. 2. Known history of brain metastases. 3. Any evidence of intra-cranial hemorrhage based on head CT scan within 30 days of enrollment. 4. History of disease progression while being treated with gemcitabine. 5. Radiotherapy of the primary tumor or unwillingness to defer radiotherapy of the primary tumor until > 3 months from initiation of treatment. 6. History of venous thromboembolism (eg, deep vein thrombosis, pulmonary embolism,and arterial thromboembolism) or other indications for anticoagulant treatment (eg,mechanical heart values, atrial fibrillation, etc.) within the last year. Local thrombus in the mesenteric or portal vein is acceptable. 7. Uncontrolled hypertension (systolic > 160 or diastolic > 100 mm Hg on medical treatment). 8. Continued anticoagulation therapy or anticoagulation therapy within 2 months prior to enrollment, except for perisurgical prophylaxis which must have ceased 2 weeks before enrollment. 9. Contraindication to systemic anticoagulation. 10. Continued treatment with antiplatelet drugs including aspirin, clopidogrel, etc. within the past 72 hours. 11. Known history of clinically significant or recurrent bleeding episodes, including significant bleeding after surgery, childbirth, or dental extraction. 12. Patients with documented invasion of adjacent organs by CT scan (e.g. stomach, duodenum) are not eligible 13. Patients known to have esophageal varicose are not eligible 14. Known history of a congenital coagulation factor deficiency. 15. Known acquired or hereditary platelet disorder. 16. Known history of immunodeficiency. 17. Women of child-bearing potential or sexually active men, unwilling to use adequate contraceptive protection during the course of the study. 18. Pregnant or lactating women (female patients of childbearing potential must have a negative serum pregnancy test within 14 days of first day of drug dosing, or if positive, pregnancy ruled out by ultrasound). 19. Laboratory Abnormalities: 1. Serum creatinine > 2 mg/dL or creatinine clearance < 50 mL/minute (using Cockroft Gault formula) 2. AST and ALT ≥ 4.0 x upper limit of normal (ULN). 3. Bilirubin ≥ 3 mg/dL. 4. Alkaline phosphatase > 5 x ULN. 5. Albumin < 2.0g/dL. 6. Hemoglobin < 9.0 g/dL. 7. Platelet count < 100,000/μL. 20. Evidence of active gastrointestinal tract bleeding, including guaiac stool positivity,excluding hemorrhoidal bleeding 21. Chronic active hepatitis B or C. 22. Known HIV infection. 23. Participation in any study of an investigational device, medication, biologic, or other agent within 30 days prior to enrollment, or planned participation within the study duration. 24. Risk factors for, or use of medications known to prolong QTc interval or that may be associate with Torsades de Pointes within 7 days of treatment start (see Appendix J. Risk Factors for Drug-induced Torsades de Pointes). 25. QTc prolongation (defined as a QTc ≥ 450 msec) or other significant ECG abnormalities including 2nd degree AV block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min). If 2 screening ECGs have a QTc ≥ 450 msec, the ECGs can be submitted for a centralized, cardiologic evaluation and if determined to be < 450 msec then the patient is eligible. ; PRIMARY OUTCOME: Number of Participants With Treatment Emergent Adverse Events (AEs); SECONDARY OUTCOME 1:

No

TRIAL NAME: Phase I/II - Allergic Adults ; BRIEF: The purposes of this study are to assess the efficacy, safety and tolerability of a single dose of REGN1908-1909 in allergic adult participants, to collect information about how much REGN1908-1909 is in blood over time and to collect information about how the body reacts to REGN1908-1909. ; DRUG USED: REGN1908-1909; DRUG CLASS: Biologic; INDICATION: Allergy; TARGET: Unknown; THERAPY: Monotherapy; LEAD SPONSOR: Regeneron Pharmaceuticals; CRITERIA: Inclusion Criteria: 1. Healthy men and women between the ages of 18 and 55 2. Positive allergen skin prick test 3. Willing and able to comply with clinic visits and study-related procedures 4. Provide signed informed consent Exclusion Criteria: 1. Persistent, chronic, or active recurring infection requiring treatment with antibiotics, antivirals, or antifungals within 4 weeks prior to the screening visit 2. Any clinically significant (determined at the investigator's discretion) abnormalities observed during the screening physical examination 3. Onset of a new exercise routine or major change to a previous exercise routine within 4 weeks prior to the screening visit. Patients must be willing to maintain a similar level of exercise for the duration of the study and to refrain from unusually strenuous exercise for the duration of the trial 4. Hospitalization for any reason within 60 days prior to the screening visit 5. Participation in any clinical research study evaluating another investigational drug or therapy within 30 days or at least 5 half-lives (whichever is longer) of the investigational drug prior to the screening visit 6. Any medical or psychiatric condition that in the opinion of the investigator or Regeneron, would place the patient at risk, interfere with participation in the study or interfere with the interpretation of study results The information listed above is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial and not all inclusion/ exclusion criteria are listed. ; PRIMARY OUTCOME: Change in allergic symptom scale score; SECONDARY OUTCOME 1: Incidence rate of treatment-emergent adverse events (TEAEs) through day 85 in participants treated with REGN1908-1909 or placebo

Yes

TRIAL NAME: Phase III - MERiDiAN - w/Paclitaxel (HER2- mBC); BRIEF: This is a Phase III, randomized, double-blind, placebo-controlled multicenter study to evaluate the efficacy and safety of bevacizumab administered in combination with paclitaxel in patients with previously untreated, locally recurrent, or metastatic HER2-negative breast cancer. Patients will be randomized to one of two treatment arms: bevacizumab or placebo. All patients will be given an intravenous (IV) infusion of of paclitaxel (90 mg/m2) for 3 weeks during each 28-day cycle. bevacizumab or placebo (10 mg/kg) will be administered by IV infusion on Days 1 and 15 of each 28-day cycle. Patients will be treated until disease progression, unacceptable toxicity or death from any cause occurs. ; DRUG USED: Avastin; DRUG CLASS: Biologic; INDICATION: Breast Cancer; TARGET: VEGF (Vascular endothelial growth factor); THERAPY: Combination; LEAD SPONSOR: Hoffmann-La Roche; CRITERIA: Inclusion Criteria: - Histologically or cytologically confirmed, HER2-negative adenocarcinoma of the breast, with measurable or non-measurable locally recurrent or metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent. - ECOG performance status of 0 or 1 - For women of childbearing potential, use of an acceptable and effective method of non-hormonal contraception - For patients who have received recent radiotherapy, recovery prior to randomization from any significant acute toxicity, and radiation treatments have to be completed more than 3 weeks from randomization Exclusion Criteria: Disease-Specific Exclusions: - HER2-positive status - Prior chemotherapy for locally recurrent or metastatic disease - Prior hormonal therapy < 2 weeks prior to randomization - Prior adjuvant or neo-adjuvant chemotherapy is allowed, provided its conclusion has been for at least 12 months prior to randomization - Investigational therapy within 28 days of randomization General Medical Exclusions: - Life expectancy of < 12 weeks - Inadequate organ function - Uncontrolled serious medical or psychiatric illness - Active infection requiring intravenous (IV) antibiotics at screening - Pregnancy or lactation - History of other malignancies within 5 years prior to screening, except for tumors with a negligible risk for metastasis or death ; PRIMARY OUTCOME: Percentage of Participants With Progression or Death in Intent-to-Treat (ITT) Population; SECONDARY OUTCOME 1: Percentage of Participants Who Died - ITT Population

Yes

TRIAL NAME: Phase I - 01; BRIEF: This is an open-label, dose-escalation Phase 1 study of the investigational agent, ON 013105. In laboratory animal studies, ON 013105 has demonstrated anti-cancer activity. The purpose of this study is to determine the highest dose of ON 013105 that can be given safely in patients with relapsed/refractory Lymphoma or B-cell Acute Lymphocytic Leukemia (Philadelphia chromosome negative). Patients will receive weekly 2-hour IV infusions of ON 013105 at higher and higher doses until intolerable side effects are observed. It is important to know the highest safe dose so additional studies can be done. ; DRUG USED: Briciclib; DRUG CLASS: New Molecular Entity (NME); INDICATION: Acute Lymphoblastic Leukemia (ALL); TARGET: Cyclin Dependent Kinase (CDK), Eukaryotic translation initiation factor 4E (eIF4E); THERAPY: Monotherapy; LEAD SPONSOR: Onconova Therapeutics, Inc.; CRITERIA: Inclusion Criteria: - ≥ 18 years of age - Documented (cytologically confirmed) relapsed/ refractory Lymphoma or B-cell Acute Lymphocytic Leukemia (Philadelphia chromosome negative) - ECOG Performance Status score of 0, 1, or 2 (see Attachment 1) - Expected survival, in the opinion of the Investigator, of at least 3 months, to allow a sufficient observation period for evaluation of ON 013105 - Recovery to at least grade I from adverse effects of prior therapies - Adequate contraceptive [including prescription oral contraceptives (birth control pills), contraceptive injections, intrauterine device (IUD), double-barrier method (spermicidal jelly or foam with condoms or diaphragm), contraceptive patch, or surgical sterilization] before entry and throughout the study for female patients of reproductive potential - Female patient with reproductive potential must have a negative serum beta-HCG pregnancy test at screening - Willing to adhere to the prohibitions and restrictions specified in this protocol - Patient (or his/her legally authorized representative) must have signed an informed consent document indicating that he/she understands the purpose of and procedures required for the study and is willing to participate in the study Exclusion Criteria: - Grade 3 thrombocytopenia (platelets <50,000/µL) or neutropenia (ANC <1000/µL) ) except if documented evidence of bone marrow involvement of lymphoma or leukemia contributing to cytopenias. - Any active malignancy within the past year except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast - History of HIV-1 seropositivity - Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia - Active infection not adequately responding to appropriate therapy. - Total bilirubin > 1.5 mg/dL not related to hemolysis or Gilbert's disease, AST/ALT > 1.5 X ULN - Serum creatinine > 1.5 mg/dL or calculated creatinine clearance < 60 ml/min. - Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of <130 Meq/L). - Women patients who are pregnant or lactating - Male patients with female sexual partners who are unwilling to follow the strict contraception requirements described in this protocol (see Section 4.4). - Major surgery without full recovery or major surgery within 3 weeks of ON 013105 treatment start. - Uncontrolled hypertension (defined as a systolic pressure ³ 180 and/or a diastolic pressure ³ 110) - New onset seizures (within 3 months prior to the first dose of ON 013105) or poorly controlled seizures - Any concurrent investigational agent or chemotherapy, radiotherapy or immunotherapy - Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements ; PRIMARY OUTCOME: Safety based on adverse events, hematology and chemical laboratory values, urinalysis, coagulation, ECG, vital signs, physical examination.; SECONDARY OUTCOME 1: Tumor response (according to Cheson, B.D., et al., Revised Response Criteria for Malignant Lymphoma, J Clin Oncol 2007. 25: p. 579-86).

No

TRIAL NAME: Phase I - ZIN-130-1505 (Healthy Volunteers); BRIEF: This study is for healthy participants. This study tests single dose of the research drug HSP-130 against two existing approved drugs United States - approved Neulasta and European Union-approved Neulasta. ; DRUG USED: Nyvepria; DRUG CLASS: Biosimilar; INDICATION: Neutropenia / Leukopenia; TARGET: Granulocyte-colony Stimulating Factor (G-CSFR)/CD114; THERAPY: Monotherapy; LEAD SPONSOR: Pfizer; CRITERIA: Inclusion Criteria: 1. Provides written informed consent approved by an Independent Ethics Committee (IEC) prior to any study related activities 2. Healthy male or female volunteers between 18 and 65 years of age (both inclusive) 3. Body mass index (BMI) between 19 and 30 kg/m^2, inclusive, and body weight of not <50 kg or >100 kg 4. Non-smoker (defined as a subject who has not smoked and has not used nicotine containing products for at least 3 months prior to study drug administration and has a negative urine screen for cotinine) at Screening 5. Female subjects of childbearing potential and male subjects and their partners of childbearing potential, agree to pregnancy prevention throughout the duration of the study (through the Follow-up Visit). Subjects and their partners must agree to use of an effective method of contraception, to avoid impregnation of females throughout the course of the study. Subjects using oral contraceptives must be on a stable regimen for at least 3 months prior to Screening. Adequate forms of contraception to be used include hormonal contraceptives (oral, patch, depot), intrauterine devices (IUD), barrier contraceptive methods, such as diaphragm, cervical cap/shield, male condoms and female condoms.Sexually active subjects must use contraception while on study drug from admission to the Follow-up Visit. Male subjects must also refrain from donating sperm from admission to the Follow-up visit 6. Willing and able to comply with the requirements of the protocol and available for the planned duration of the study Exclusion Criteria: 1. Any active systemic or immunologic disease or condition, including but not limited to the following general categories: cardiovascular/pulmonary, hepatorenal, or systemic infection, or lactation 2. History of, or current, malignancy with the exception of adequately treated squamous or basal cell carcinoma of the skin or cervical carcinoma in situ within 5 years 3. Any disease or condition that might interfere with the absorption, distribution, metabolism, or excretion of the study drug or would place the subject at increased risk 4. Hematologic laboratory abnormalities including leukocytosis (defined as total leukocytes >11,000/μL), leukopenia (defined as total leukocytes <4000/μL), neutropenia (defined as ANC <1500/μL) or thrombocytopenia (defined as platelet count of <150/μL) 5. Clinically significant, as judged by the investigator, vital sign or 12-lead ECG abnormality 6. History of biological growth factor exposure, including but not limited to filgrastim and other granulocyte-colony stimulating factors in the context of treatment, prophylaxis, peripheral blood stem cell mobilization, or previous investigational study setting. This also includes exclusion for history of interferon, epoetin, and intravenous immunoglobulin (IVIG) exposure 7. Receipt of live vaccination, or exposure to communicable viral diseases such as, varicella, mumps, or measles within the 4 weeks prior to Screening 8. Surgery within the 4 months prior to Screening 9. Use of any prescription medicine (with the exception of contraceptives) within 7 days or at least 5 half-lives, whichever is longer. Use of oral or parenteral anticoagulant or antiplatelet agents and corticosteroids should be specifically queried 10. Administration of a drug by depot injection (with exception of depot contraception) within 30 days prior to Randomization or 5 half-lives of that drug, whichever is longer 11. Use of over the counter medications, including aspirin and non-steroidal anti-inflammatory drugs, or natural preparations (dietary supplement or herbal product) within 7 days or at least 5 half-lives, whichever is longer. Vitamins and calcium are allowed (not to exceed 100% Daily Value) 12. History of drug or alcohol abuse within 2 years prior to Randomization, as determined by the investigator or a positive urine screen for drugs of abuse (UDS) at Screening. Screening for drugs of abuse will minimally include cannabinoids, opiates, barbiturates, amphetamines, cocaine, benzodiazepines, and alcohol 13. Drug sensitivity, allergic reaction to, or known hypersensitivity/idiosyncratic reaction to Escherichia coli-derived proteins, filgrastim, other granulocyte-colony stimulating factors, or pegylated agents 14. History of splenic rupture (or subject who is asplenic), pulmonary infiltrate or pneumonia, sickle cell disease, chronic neutropenia, thrombocytopenia, or vasculitis 15. Any clinically significant, as determined by the investigator, abnormal laboratory evaluations, including human immunodeficiency virus antibody (HIVAb), hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibody (HCVAb), and liver function including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 1.5 the upper limit of normal taken at Screening. Negative HIVAb status will be confirmed at Screening and the results will be maintained confidentially by the study site 16. Donated or lost 475 mL or more blood volume (including plasmapheresis) or had a transfusion of any blood product within 3 months prior to Screening 17. Participated in another clinical research study with administration of investigational drug within 30 days prior to Randomization 18. Potentially not be able to comply with the requirements of this clinical trial, to communicate effectively with study personnel, or is considered by the Investigator, for any reason, to be an unsuitable candidate for the study ; PRIMARY OUTCOME: Area under the effect versus time curve for absolute neutrophil count (ANC) from the time of dose administration to 288 hours after dose administration (AUECANC); SECONDARY OUTCOME 1: Time of maximum value for ANC (ANC_Tmax)

Yes

TRIAL NAME: Phase I/II - Transpher A Study; BRIEF: The main objective of this study is to evaluate the efficacy and safety of ABO-102 for the treatment of MPS IIIA. ; DRUG USED: ABO-102; DRUG CLASS: Biologic; INDICATION: Mucopolysaccharidosis IIIA (MPS IIIA; Sanfilippo A Syndrome); TARGET: Heparan-N-sulfatase (N-sulphoglucosamine sulphohydrolase, sulfamidase), N-sulfo-D-glucosamine; THERAPY: Monotherapy; LEAD SPONSOR: Ultragenyx Pharmaceutical Inc; CRITERIA: Inclusion Criteria: - Diagnosis of MPS IIIA confirmed by the following methods: - No detectable or significantly reduced SGSH enzyme activity by leukocyte assay, and - Genomic DNA analysis demonstrating homozygous or compound heterozygous mutations in the SGSH gene - Age: From birth to 2 years or children older than 2 years with a minimum cognitive Developmental Quotient (DQ) of 60 or above (calculated by Bayley Scales of lnfant and Toddler Development - Third Edition) Exclusion Criteria: - Inability to participate in the clinical evaluation as determined by Principal Investigator (PI) - Identification of two nonsense or null variants on genetic testing of the SGSH gene - At least one S298P mutation in the SGSH gene - Has evidence of an attenuated phenotype of MPS IIIA - Presence of a concomitant medical condition that precludes lumbar puncture or use of anesthetics - Active viral infection based on clinical observations - Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer or precludes the child from participating in the protocol assessments and follow up - Subjects with total anti-AAV9 antibody titers ≥ 1:100 equivalent to a positive screen as determined by ELISA in serum - Subjects with a positive response for the enzyme-linked immunosorbent spot (ELISpot) for T-cell responses to AAV9 - Serology consistent with exposure to HIV, or serology consistent with active hepatitis B or C infection - Bleeding disorder or any other medical condition or circumstance in which a lumbar puncture (for collection of CSF) is contraindicated according to local institutional policy - Visual or hearing impairment sufficient to preclude cooperation with neurodevelopmental testing - Uncontrolled seizure disorder - Any item (braces, etc.) which would exclude the subject from being able to undergo MRI according to local institutional policy - Any other situation that precludes the subject from undergoing procedures required in this study - Subjects with cardiomyopathy or significant congenital heart abnormalities - The presence of significant non-MPS IlIA related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study - Abnormal laboratory values Grade 2 or higher as defined in CTCAE v4.03 for GGT, total bilirubin, creatinine, hemoglobin, WBC count, platelet count, PT and aPTT - Female participant who is pregnant or demonstrates a positive urine or bhCG result at screening assessment (if applicable) - Any vaccination with viral attenuated vaccines less than 30 days prior to the scheduled date of treatment (and use of prednisolone) - Previous treatment by Hematopoietic Stem Cell transplantation - Previous participation in a gene/cell therapy or enzyme replacement therapy (ERT) clinical trial ; PRIMARY OUTCOME: Change from Baseline in Cognitive Domain Bayley Scales of Infant and Toddler Development Raw Scores-Third edition (BSID-III); SECONDARY OUTCOME 1: Change From Baseline in Vineland Adaptive Behavior Scale II-Survey Interview Form

No

TRIAL NAME: Phase II - ZA-201; BRIEF: This double-blind, randomized, comparator-controlled Phase II study is designed to establish the safety and efficacy of Zoenasa Rectal Gel compared to mesalamine enema in subjects with left-sided ulcerative colitis, as measured by the modified ulcerative colitis disease activity index (UCDAI), over 6 weeks of treatment. In this study, two cohorts of subjects will receive either Zoenasa-1:4 (1.0g NAC; 4.0g 5-ASA) investigational drug enema therapy or comparator mesalamine enema (4.0g 5-ASA). The study will enroll subjects randomized equally into the 2 cohorts. Each cohort will enroll approximately 60 subjects. The two arms of the trial will be enrolled concurrently in a randomized fashion. ; DRUG USED: Zoenasa; DRUG CLASS: Non-NME; INDICATION: Ulcerative Colitis (UC); TARGET: Cyclooxygenases (COX-1, COX-2, and COX-3), EGFR (Epidermal Growth Factor Receptor), NF-Kappa B (nuclear factor kappa-light-chain-enhancer of activated B cells) , PPAR gamma; THERAPY: Monotherapy; LEAD SPONSOR: Altheus Therapeutics, Inc.; CRITERIA: Inclusion Criteria: - Male and female subjects are eligible if they are ≥ 18 years of age and ≤ 64 years. - They have a documented history of idiopathic ulcerative colitis based on endoscopic and/or histologic findings involving the left side of the colon, with mild to moderate active disease. - Eligible subjects will have a documented history of ulcerative colitis, and a modified UCDAI score of 4-10, inclusive, with a Physician's rating of disease score of 2 points or less (mild or moderate active ulcerative colitis), rectal bleeding score of 1 or more (based on subject diary), and mucosal appearance score (based on endoscopy) of 1 point or more at baseline. - Laboratory data: - White blood cell count between 4.0 - 12.0 K/mm3 - Platelet count: 150 - 500 K/mm3 - Hemoglobin > 10.0 g/dL - Total bilirubin < 1.5 mg/dL - Aspartate aminotransferase < 100 u/dL - Alanine aminotransferase < 100 u/dL - Alkaline phosphatase < 250 u/dL - Blood urine nitrogen < 40 mg/dL - Creatinine < 1.5 mg/dL - Satisfies one of the following: - Female subjects of childbearing potential must have a negative urine pregnancy test at screening; surgically sterile, post-menopausal, abstinent, or patient or partner agree to use a medically appropriate form of birth control from screening to until 1 month after the last dose of study medication. - Male subjects must be surgically sterile, abstinent, or patient or partner compliant with a contraceptive regimen from screening to until 1 month after the last dose of study medication. - They are able to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures. Exclusion Criteria: - They have documented history of proximal or universal ulcerative colitis, proctitis or active proctitis confined to 15cm or less from the anal verge. - They demonstrate signs and symptoms of fulminant colitis, bowel stricture, toxic megacolon, an anticipated need for blood transfusion for gastrointestinal bleeding, or demonstrate evidence of peritonitis. - They receive a Physician's rating of disease severity as part of the modified UCDAI of 3 (severe disease) or an aggregate score of 11 or greater. - They have shown prior documented history of evidence of high grade dysplasia on biopsy from endoscopic examinations. - Their stool contains enteric pathogens or Clostridium difficile toxins. - They have a history of recurrent Clostridium difficile infection. - They have prior history of biologic therapy within the previous 4 years. - They have received systemic steroids or immunosuppressants within the previous 4 weeks. - Treatment in the last 14 days that included antibiotic, antifungal, antiparasitic medications, or rectally administered steroids (e.g. Cortenema®) or mesalamine enema (Rowasa®). - Treatment in the last 7 days that included mesalamine (5-ASA) via oral administration (e.g. Asacol®, Lialda®, balsalazide, etc). - They have a history of cancer (defined as malignancy within 5 years except for squamous cell or basal cell cancers of the skin), asthma, or bronchospasm. - Positive pregnancy test or lactating subjects. - There is evidence of chemical substance abuse. - They have had repeated anti-inflammatory drug treatment (longer than 3 days at doses that exceed those available without a prescription) within the previous 7 days (with exception of aspirin at doses of 325mg/day or less for prophylaxis of cardiac disease), or initiated new non-steroidal anti-inflammatory (NSAID) treatment within the last 30 days. - They have a known allergy to N-acetylcysteine or mesalamine, or have a history of serious AEs related to their use (including, but not limited to pancreatitis or hepatitis). - They have a history of failure to retain enemas. - Other clinically significant diseases that could interfere with the protocol compliance appear. These would include clinically important hematological, renal, hepatic, metabolic, psychiatric, central nervous system (CNS), pulmonary or cardiovascular disease. - Use of any investigational medication within the previous 90 days. - Any condition which the study physician judges to preclude safe participation in the study or to confound the evaluation of the study outcome. ; PRIMARY OUTCOME: Change in modified UCDAI at 6 weeks; SECONDARY OUTCOME 1: Change in modified UCDAI at 3 weeks

No

TRIAL NAME: Phase IIb - DOVE (VVC); BRIEF: This is a multicenter, randomized, double-blind, double-dummy, active-controlled, dose-finding study to compare the efficacy, safety and tolerability of oral SCY-078 versus oral fluconazole in adult female subjects 18 years and older with moderate to severe Acute Vulvovaginal Candidiasis (AVVC). Approximately 180 eligible subjects (30 subjects per treatment group) will be enrolled and randomized into the study. ; DRUG USED: Brexafemme; DRUG CLASS: New Molecular Entity (NME); INDICATION: Fungal Infections - Non-Systemic; TARGET: Beta (1,3)-D-Glucan; THERAPY: Monotherapy; LEAD SPONSOR: Scynexis, Inc.; CRITERIA: Key Inclusion Criteria: 1. Subject is a female of at least 18 years of age 2. Subject has a diagnosis of symptomatic AVVC at baseline including a positive microscopic examination with 10% KOH in a vaginal sample revealing yeast forms (hyphae/pseudohyphae) or budding yeasts, and vaginal pH (≤4.5) Key Exclusion Criteria: 1. Subject has any vaginal condition other than AVVC that may interfere with the diagnosis or evaluation of response to therapy, such as suspected or confirmed concurrent causes of vulvovaginitis and/or cervicitis (mixed infection) 2. Need for systemic and/or topical (vaginal) antifungal treatment, including prescription or over-the-counter products during the study and treatment for VVC 28 days prior to randomization 3. Subject is actively menstruating at the time of the Baseline visit. 4. Subject has uncontrolled diabetes mellitus. 5. Subject has a vaginal sample with pH >4.5. 6. Subject has a history of or an active cervical/vaginal cancer. ; PRIMARY OUTCOME: Clinical Cure (Complete Resolution of Signs and Symptoms); SECONDARY OUTCOME 1: Co-occurrence of Clinical and Mycological Cure

Yes

TRIAL NAME: Phase II - NCI; BRIEF: This randomized phase II trial studies how well temozolomide with or without veliparib works in treating patients with small cell lung cancer that has returned or does not respond to treatment. Temozolomide works by damaging molecules inside the cancer cells, such as deoxyribonucleic acid (DNA), that are needed for cancer survival and growth. Veliparib may stop the growth of tumor cells by blocking proteins that are needed for repairing the damaged DNA and it may also help temozolomide to kill more cancer cells. It is not yet know whether temozolomide is more effective with or without veliparib in treating patients with relapsed or refractory small cell lung cancer. ; DRUG USED: Veliparib; DRUG CLASS: New Molecular Entity (NME); INDICATION: Small Cell Lung Cancer (SCLC); TARGET: Poly ADP-Ribose Polymerase (PARP); THERAPY: Combination; LEAD SPONSOR: National Cancer Institute (NCI); CRITERIA: Inclusion Criteria: - Patients must have histologically or cytologically confirmed small cell lung cancer; confirmation will be done at Memorial Sloan-Kettering Cancer Center (MSKCC) or locally for participating sites - Patients' disease has relapsed or progressed after one or two prior chemotherapy regimens, one of which must have been an etoposide-platinum doublet; eligible patients will be defined as follows: - "Sensitive" disease: patients who had one previous line of chemotherapy and maintained an appropriate response for > 60 days - "Refractory" disease: those patients with either (a) no response to first-line chemotherapy or progression =< 60 days after completing treatment, or (b) "sensitive" or "refractory" disease in need of third-line therapy (i.e. completed or failed two previous lines of chemotherapy) - Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%) - Patients with asymptomatic brain metastases that do not require immediate whole brain radiation therapy and are on stable doses of steroids are allowed - Patients must have measurable disease, which is defined as at least one lesion that can be accurately measured in at least one dimension on a computed tomography (CT) scan as per RECIST version 1.1; brain metastases can be considered measurable disease if they meet this criterion - Absolute neutrophil count >= 1,500/mcL - Platelets >= 100,000/mcL - Hemoglobin >= 8.5 g/dL; the use of transfusion to achieve this criterion should be at the discretion of the investigators - Total bilirubin =< 1.5 mg/dL x institutional upper limit of normal - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional upper limit of normal - Creatinine =< 1.5 x institutional upper limit of normal OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels >= 1.5 x upper limit of institutional normal - Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately - For women of child-bearing potential, negative pregnancy test within 14 days prior to starting temozolomide and ABT-888 - Ability to understand and the willingness to sign a written informed consent document - Able to swallow pills - Patients will not be excluded based on the diagnosis of acquired immune deficiency syndrome (AIDS); given the increased risk of infection, these patients should have cluster of differentiation (CD)4 counts above 200 cells/mm^3; patients with AIDS or human immunodeficiency virus (HIV) not receiving agents with the potential for pharmacokinetic interactions with ABT-888 may be eligible Exclusion Criteria: - Patients who have had chemotherapy or radiotherapy within 3 weeks prior to entering the study - Patients who have not recovered from adverse events due to agents administered more than 3 weeks earlier; toxicities should have resolved to baseline or to within one grade level of their baseline (not to exceed grade 2) - Patients who have been administered ABT-888, any other PARP-inhibitor, or temozolomide - Patients may not be receiving any other investigational agents - Patients with leptomeningeal involvement - Patients with active seizures or a history of seizures - History of allergic reactions attributed to compounds of similar chemical or biologic composition to ABT-888 or temozolomide - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ABT-888; these potential risks also apply to temozolomide - Patients with either AIDS or HIV on combination antiretroviral therapy are ineligible - Patients with a synchronous active malignancy requiring treatment ; PRIMARY OUTCOME: Progression-free Survival, Calculated as the Proportion of Patients Alive and Without Evidence of Disease; SECONDARY OUTCOME 1: Overall Response (ORR) by RECIST 1.1 Criteria

Yes

TRIAL NAME: Phase III - 1st Line vs. Gleevec; BRIEF: Masitinib in First Line Treatment of Gastro-Intestinal Stromal Tumor (GIST) ; DRUG USED: Masitinib; DRUG CLASS: New Molecular Entity (NME); INDICATION: Gastrointestinal Stromal Tumor (GIST); TARGET: Fibroblast Growth Factor Receptor (FGFR) , KIT/c-KIT, Platelet-derived growth factor receptor (PDGFR); THERAPY: Monotherapy; LEAD SPONSOR: AB Science; CRITERIA: Main inclusion criteria include: - Histologically proven, metastatic or locally advanced non resectable, or recurrent post-surgery GIST - Naïve patient or patient previously treated with imatinib as neoadjuvant/adjuvant who relapsed after imatinib discontinuation - c-Kit (CD117) positive tumours detected by immuno-histochemically or PDGFR positive if c-Kit negative Main exclusion criteria include: - Patient previously treated by tyrosine kinase inhibitors except imatinib in case of inclusion criteria - Patient treated for a cancer other than GIST within 5 years before enrolment, with the exception of basal cell carcinoma or cervical cancer in situ - Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis ; PRIMARY OUTCOME: Progression Free Survival (PFS); SECONDARY OUTCOME 1: Overall Survival (OS)

No

TRIAL NAME: Phase I - Healthy Males; BRIEF: This is a phase 1b, open-label, single dose study in healthy male subjects. Approximately 12 healthy male subjects will receive a subcutaneous injection of denosumab on Day 1. Subjects will be followed by a 105 day treatment-free follow-up period. ; DRUG USED: Prolia (Osteoporosis); DRUG CLASS: Biologic; INDICATION: Osteoporosis / Osteopenia; TARGET: RANK Ligand (RANKL); THERAPY: Monotherapy; LEAD SPONSOR: Amgen; CRITERIA: Inclusion Criteria: Subject has provided informed consent; Healthy male between ≥40 to ≤ 65 years of age (inclusive) at the time of enrollment; Subject must be willing and able to produce a semen sample on seven separate study visits; Subject must be willing to refrain from ejaculation for a 48 hour period prior to each sample collection; Exclusion Criteria: Any condition or drug therapy that might interfere with the subjects ability to ejaculate and produce a semen sample; Clinically significant abnormality during the screening physical examination, ECG, or laboratory evaluation; Known history of blood in urine or semen; Osteonecrosis of the jaw (ONJ) or risk factors for ONJ such as invasive dental procedures (eg, tooth extraction, dental implants, oral surgery in the past 6 months), poor oral hygiene, periodontal and/or pre-existing dental disease; Recent tooth extraction (within 6 months of screening visit); Evidence of hypocalcemia at screening; Known vitamin D deficiency; Malignancy (except non-melanoma skin cancers) within the last 5 years; Positive for human immunodeficiency virus (HIV) at screening or known diagnosis of AIDS; Positive Hepatitis B Surface Antigen (HepBsAg) (indicative of chronic Hepatitis B) or detectable Hepatitis C virus Ribonucleic acid (RNA) by Polymerase Chain Reaction (PCR) at screening (indicative of active Hepatitis C - screening is generally done by Hepatitis C Antibody (HepCAb), followed by Hepatitis C virus RNA by PCR if HepCAb is positive); History of hypersensitivity or allergic reaction to mammalian cell derived drug products or sensitivity to any of the products or components to be administered during dosing; Known intolerance to calcium or vitamin D supplements; Subject previously has entered this study or has been previously exposed to denosumab in the past 12 months; Has donated or lost ≥ 400 mL of blood or plasma within 8 weeks prior to screening; Positive urine screen for alcohol and/or potential drugs of abuse at screening unless medication is prescribed by a physician and approved by the Investigator and Amgen; Known alcohol abuse or use of illicit drugs within 12 months of enrollment; Subject is unwilling or unable to limit alcohol consumption throughout the course of the study. Alcohol is prohibited 24 hours prior to screening and administration of investigational product. Alcohol is limited to no more than 2 drinks per day for the duration of the study; where a standard drink is equivalent to 12 ounces of regular beer, 8-9 ounces of malt liquor, 5 ounces of wine, or 1.5 ounces of 80 proof distilled spirits; Currently receiving treatment in another investigational device or drug study, or less than 30 days or 5 half-lives (whichever is longer) since ending treatment on another investigational device or drug study(s). Other investigational procedures while participating in this study are excluded; Use of any non-Amgen approved over-the-counter or prescription medications, within the 14 days or 5 half-lives (whichever is longer), prior to receiving the dose of denosumab. Acetaminophen (up to 2 g per day) for analgesia and hormone replacement therapy (eg, androgen, thyroid) will be allowed. Other medications may be approved following review by the Principal Investigator and the Amgen Medical Monitor. Written documentation of this review and Amgen acknowledgement is required for subject participation; Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and Investigator's knowledge; Subject has any kind of disorder that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures; History or evidence of any other clinically significant disorder, condition or disease that, in the opinion of the Investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion ; PRIMARY OUTCOME: Maximum Observed Concentration (Cmax) of Denosumab in Seminal Fluid; SECONDARY OUTCOME 1: Maximum Observed Concentration (Cmax) of Denosumab in Serum

Yes

TRIAL NAME: Phase II/III - BHV3000-305 (Migraine Prevention); BRIEF: The purpose of this is study is to compare the efficacy of BHV-3000 (rimegepant) to placebo as a preventive treatment for migraine, as measured by the reduction in the number of migraine days per month. ; DRUG USED: Nurtec ODT; DRUG CLASS: New Molecular Entity (NME); INDICATION: Migraine and Other Headaches; TARGET: Calcitonin Gene-Related Peptide (CGRP) / Receptor; THERAPY: Monotherapy; LEAD SPONSOR: Pfizer; CRITERIA: Inclusion Criteria: 1. Subject has at least 1 year history of migraine (with or without aura) consistent with a diagnosis according to the International Classification of Headache Disorders, 3rd Edition, including the following: 1. Age of onset of migraines prior to 50 years of age 2. Migraine attacks, on average, lasting 4 - 72 hours if untreated 3. Per subject report, 4 - 18 migraine attacks of moderate to severe intensity per month within the last 3 months prior to the Screening Visit 4. 6 or more migraine days during the Observation Period 5. Not more than 18 headache days during the Observation Period 6. Ability to distinguish migraine attacks from tension/cluster headaches 7. Subjects on prophylactic migraine medication are permitted to remain on 1 medication with possible migraine-prophylactic effects if the dose has been stable for at least 3 months prior to the Screening Visit, and the dose is not expected to change during the course of the study. Exclusion Criteria: 2. Subject with a history of HIV disease 3. Subject history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Subjects with Myocardial Infarction (MI), Acute Coronary Syndrome (ACS), Percutaneous Coronary Intervention (PCI), cardiac surgery, stroke or transient ischemic attack (TIA) during the 6 months prior to screening 4. Uncontrolled hypertension (high blood pressure), or uncontrolled diabetes (however subjects can be included who have stable hypertension and/or diabetes for at least 3 months prior to screening). 5. Subjects with major depressive episode within the last 12 months, major depressive disorder or any anxiety disorder requiring more than 1 medication for each disorder. Medications to treat major depressive disorder or an anxiety disorder must have been at a stable dose for at least 3 months prior to the Screening visit. 6. Subjects with other pain syndromes, psychiatric conditions, dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion, might interfere with study assessments 7. Subject has a history of gastric, or small intestinal surgery (including Gastric Bypass, Gastric Banding, Gastric Sleeve, Gastric Balloon, etc.), or has disease that causes malabsorption 8. Body mass index ≥ 33 kg/m2 9. Subject has current diagnosis of major depressive disorder requiring treatment with atypical antipsychotics, schizophrenia, bipolar disorder, or borderline personality disorder 10. History of gallstones or cholecystectomy. 11. The subject has a history or current evidence of any unstable medical conditions (e.g., history of congenital heart disease or arrhythmia, known or suspected infection, hepatitis B or C, or cancer) that, in the investigator's opinion, would expose them to undue risk of a significant adverse event (AE) or interfere with assessments of safety or efficacy during the course of the trial. ; PRIMARY OUTCOME: Change From Baseline in the Mean Number of Total Migraine Days Per Month in the Last 4 Weeks of the DBT Phase; SECONDARY OUTCOME 1: Number of Participants Who Had ≥ 50% Reduction in Moderate or Severe Migraine Days Per Month in the Last 4 Weeks of the DBT Phase

Yes

TRIAL NAME: Phase IIb - 002 (ARDS); BRIEF: This phase IIb, randomized, placebo-controlled, double-blind, dose escalation study will assess the local and systemic safety of 7 days orally inhaled sequential multiple ascending doses of solnatide in patients with pulmonary permeability oedema and moderate-to-severe ARDS and review potential efficacy endpoints for a future phase III pivotal trial. ; DRUG USED: AP301; DRUG CLASS: New Molecular Entity (NME); INDICATION: Acute Respiratory Failure, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS); TARGET: Tumor Necrosis Factor-alpha (TNF-alpha); THERAPY: Monotherapy; LEAD SPONSOR: Apeptico Forschung und Entwicklung GmbH; CRITERIA: Inclusion Criteria: 1. Informed consent 2. Male or female ≥18 years of age. 3. Patient has been admitted to an ICU, is mechanically ventilated (according to the ventilation and weaning protocol in Appendix I) and stable in this condition for at least 8 hours. 4. Moderate-to-severe ARDS diagnosis as defined by the Berlin Definition: - Onset of ARDS within 1 week of a known clinical insult or new or worsening respiratory symptoms. - Bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules. - Respiratory failure not fully explained by cardiac failure or fluid overload (origin of oedema). - PaO2/FiO2 ≤ 200 mm Hg with Positive End-Expiratory Pressure (PEEP) ≥5 cm H2O. 5. ARDS diagnosis not older than 48 hours. 6. Extravascular lung water index (EVLWI) ≥ 10 ml/PBW as assessed with a validated bedside measurement (single indicator transpulmonary thermodilution measurement with the PiCCO® system). 7. Patient who meets criteria for extensive hemodynamic monitoring as per international intensive care medicine standards. 8. For patients that are temporarily unable to consent (e.g. comatose patients) a subsequent informed consent has to be provided. 9. Male and Female (WOCBP) patients using adequate contraception. Exclusion Criteria: 1. History of clinically relevant allergies or idiosyncrasies to solnatide. 2. Known use of any other investigational or non-registered drug within 30 days prior to study enrolment. 3. Severe state of septic shock with a Mean Arterial Pressure (MAP) ≤ 65 mm Hg and a serum lactate level > 4 mmol/L (36 mg/dL) despite adequate volume resuscitation. 4. An underlying clinical condition that, in the opinion of the Investigator, would make it very unlikely for the patient to be successfully weaned from ventilation due to severe underlying diseases (e.g. severe malnutrition, severe neurological diseases, pulmonary fibrosis or COPD). 5. Extra-corporeal membrane oxygenation, high-frequency oscillatory ventilation or any form of extra-corporeal lung support. In no way are patients to be denied or delayed these procedures to avoid exclusion from the study. 6. Neutrophil count < 0.3 x 109/L. 7. Cancer treatment (chemotherapy or biological) or therapy with other immunosuppressive agents for organ transplantation within 2 weeks. 8. Cachexia (BMI < 18.5 kg/m2). 9. Cardiogenic pulmonary oedema diagnosed by echocardiography or pulmonary artery catheter. 10. Severe skin burns involving more than 15% of body surface. 11. Subjects who are extremely unlikely to survive more than 48 hours due to the acute conditions of the patient in the opinion of the Investigator. 12. Subjects transferred from a hospital not participating in this study who are already planned to be re-transferred during the observation period. 13. Subjects who are not expected to survive the next month because of an underlying uncorrectable medical condition or a do not resuscitate order. 14. Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test. ; PRIMARY OUTCOME: Safety endpoint: Any cause death; SECONDARY OUTCOME 1: EVLWI

No

TRIAL NAME: Phase III - EMBARK; BRIEF: The purpose of this study is to assess enzalutamide plus leuprolide in patients with high-risk nonmetastatic prostate cancer progressing after radical prostatectomy or radiotherapy or both. The randomized / blinded portion of the study is now completed following primary endpoint analyses. The study remains ongoing in open label format. ; DRUG USED: Xtandi; DRUG CLASS: New Molecular Entity (NME); INDICATION: Prostate Cancer; TARGET: Androgen receptors; THERAPY: Monotherapy and Combo Therapy; LEAD SPONSOR: Pfizer; CRITERIA: Inclusion Criteria: - Histologically or cytologically confirmed adenocarcinoma of the prostate at initial biopsy, without neuroendocrine differentiation, signet cell, or small cell features; - Prostate cancer initially treated by radical prostatectomy or radiotherapy (including brachytherapy) or both, with curative intent; - PSA doubling time ≤ 9 months; - Screening PSA by the central laboratory ≥ 1 ng/mL for patients who had radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer and at least 2 ng/mL above the nadir for patients who had radiotherapy only as primary treatment for prostate cancer; - Serum testosterone ≥ 150 ng/dL (5.2 nmol/L). Exclusion Criteria: - Prior or present evidence of distant metastatic disease as assessed by radiographic imaging; - Prior hormonal therapy. Neoadjuvant/adjuvant therapy to treat prostate cancer ≤ 36 months in duration and ≥ 9 months before randomization, or a single dose or a short course (≤ 6 months) of hormonal therapy given for rising PSA ≥ 9 months before randomization is allowed.; - Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, or enzalutamide for prostate cancer; - Prior systemic biologic therapy, including immunotherapy, for prostate cancer; - Major surgery within 4 weeks before randomization; - Treatment with 5-α reductase inhibitors (finasteride, dutasteride) within 4 weeks of randomization; - Known or suspected brain metastasis or active leptomeningeal disease; - History of another invasive cancer within 3 years before screening, with the exception of fully treated cancers with a remote probability of recurrence ; PRIMARY OUTCOME: Metastasis-free survival (MFS); SECONDARY OUTCOME 1: Overall survival

No

TRIAL NAME: Phase II - 37202 (Stanford); BRIEF: This is a randomized, sham controlled, masked clinical trial of 60 study participants with glaucoma. Participants with a qualifying study eye will be randomized after screening and baseline evaluations to receive the NT-501 encapsulated cell therapy (ECT) implant or a sham surgery (control arm), and no explant will be required. An examination for safety will occur one day and one week following implant and periodically thereafter for 24 months post-implant. Based on the primary analysis of data at 6 months, patients in the control arm may be offered the NT-501 ECT implant at the 12 month time point. ; DRUG USED: Renexus; DRUG CLASS: Biologic; INDICATION: Glaucoma / Ocular Hypertension (Ophthalmology); TARGET: Ciliary Neurotrophic Factor Receptor (CNTFR); THERAPY: Monotherapy; LEAD SPONSOR: Stanford University; CRITERIA: Inclusion Criteria: Patients must meet all of the following criteria to join the study (all eligibility criteria must be met at the screening and baseline visits unless otherwise noted): 1. Participant must be medically able to undergo the testing required in the schedule of events (SOE). 2. Participant's clinical diagnosis must be consistent with glaucoma 1. characterized by the following features: a) Clinical evidence of progressive retinal ganglion cell (RGC) dysfunction and degeneration using both visual field and at least one structural modality as established by: i. Glaucomatous visual field abnormality. ii. Mean deviation (MD) of -3 to -15 dB. iii. Minimum average retinal nerve fiber layer (RNFL) thickness of 60 μm and maximum average RNFL of 90 μm. b) Residual visual field preservation including best-corrected visual acuity (BCVA) better than 20/200 in both eyes. c) Two visual field tests of adequate quality with a maximum visual field index (VFI) variability of ± 10%. 3. Participant's glaucoma must be clinically stable, with intraocular pressure (IOP) < 21. 4. If a participant has two eyes meeting study criteria, only the worse eye as determined by visual field index (VFI) will be deemed includable. If both eyes qualify and have the same VFI, a randomization procedure will assign one eye to the study. 5. Participant must understand and sign the informed consent. If the participant's vision is impaired to the point where he/she cannot read the informed consent document, the document will be read to the participant in its entirety. 6. Females of childbearing potential must agree to use an effective form of birth control. 7. Participant must be determined by the presurgical anesthesia or medical team to be fit for ophthalmic surgery for the NT-501 ECT implant insertion. Exclusion Criteria: 1. Participant is unable to comply with study procedures or follow-up visits. 2. Participant has other optic nerve or retinal degenerative disease causing vision loss, irrespective of whether it is currently treated or untreated. 3. Participant has visual loss to less than 20/200 in non-study eye. 4. Participant is likely to be offered glaucoma surgery within 6 months of screening. 5. Participant has optic nerve atrophy beyond modest pallor. 6. Participant has cataract-associated vision loss to less than 20/40. 7. Participant has a history of ocular herpes zoster. 8. Participant has a requirement of acyclovir and/or related products during study duration. To be eligible for this study, the participant must discontinue use of these products prior to enrollment and must not continue with the products until after they have completed the study. 9. Participant has evidence of corneal opacification or lack of optical clarity. 10. Participant has uveitis or other ocular inflammatory disease. 11. Participant is receiving systemic steroids or other immunosuppressive medications. 12. Participant has diabetic macular edema and/or diabetic retinopathy. 13. Participant has myopic degeneration. 14. Participant is currently participating in or has within the last 3 months participated in any other clinical trial of a drug by ocular or systemic administration. 15. Participant is pregnant or lactating. 16. Participant is on chemotherapy. 17. Participant has a history of malignancy other than basal cell carcinoma, unless it was treated successfully 2 years prior to inclusion in the trial. 18. Participant has, in the opinion of the investigator, any physical or mental condition that would increase the risk of participation in the study or may interfere with the study procedures, evaluations and outcome assessments. 19. Participant has choroidal neovascularization secondary to age related macular degeneration or any other type of retinal degeneration that may interfere with the study procedures, evaluations and outcome assessments. 20. Any intraocular surgery of the study eye within 12 weeks prior to the screening visit 21. History of use of drugs with known retinal toxicity, at retinotoxic doses. 22. Participant has a history or current non-arteritic anterior ischemic neuropathy (NAION) 23. Patient has a history of multiple sclerosis. 24. Participant has glaucoma that is not considered open angle glaucoma, pseudoexfoliation glaucoma or pigmentary glaucoma.. ; PRIMARY OUTCOME: Visual Field; SECONDARY OUTCOME 1: Structural measure of retinal ganglion cell layer thickness

No

TRIAL NAME: Phase III - A303 (Ext.); BRIEF: Study to assess the long term safety and tolerability of daridorexant in adult and elderly subjects suffering from difficulties to sleep ; DRUG USED: Daridorexant; DRUG CLASS: New Molecular Entity (NME); INDICATION: Insomnia; TARGET: Hypocretin/orexin receptor ; THERAPY: Monotherapy; LEAD SPONSOR: Idorsia Pharmaceuticals Ltd.; CRITERIA: Inclusion Criteria: - Signed informed consent prior to any study-mandated procedure (Visit 1). - Having completed the DB study treatment and the run-out period of ID-078A301 (NCT03545191) or ID-078A302 (NCT03575104). - For woman of childbearing potential, the following is required: - Negative urine pregnancy test (EOT of ID-078A301 or ID-078A302 studies) - Agreement to use the contraception scheme as required by the protocol from Visit 1 up to at least 30 days after EODBT. Exclusion Criteria: - Unstable medical condition, significant medical disorder or acute illness, C-SSRS©, ECG, hematology or biochemistry test results in ID-078A301 and ID-078A302, which in the opinion of the investigator could affect the subject's safety or interfere with the study assessments (Visit 1). - For female subjects: lactating or planning to become pregnant during the duration of the study (Visit 1). - Positive urine drug test (for benzodiazepines, barbiturates, cannabinoids, opiates, amphetamines, or cocaine) or presence of alcohol in exhaled breath as detected by breathalyzer test (EOT of ID-078A301 or ID-078A302 studies if same day as Visit 1 or Visit 1 if within 7 days after EOT). ; PRIMARY OUTCOME: Total no. of Subjects With at Least One TEAE; SECONDARY OUTCOME 1:

Yes

TRIAL NAME: Phase I - HIBM CL101; BRIEF: Hereditary Inclusion Body Myopathy (HIBM) is a severe progressive metabolic myopathy caused by a defect in the biosynthetic pathway for sialic acid (SA), a critical component of many muscle proteins, resulting in a deficiency in SA in the muscles of HIBM patients. The effective replacement of the missing SA substrate is theoretically simple, and, in animal models, replacement with SA showed significant restoration of sialylation biochemistry and excellent reduction in muscle disease. These data show that replacement can achieve significant clinical benefit in muscle pathology, function, and survival. ; DRUG USED: Ace-ER; DRUG CLASS: New Molecular Entity (NME); INDICATION: GNE-Related Myopathy (Inclusion Body Myopathy 2); TARGET: Protein synthesis; THERAPY: Monotherapy; LEAD SPONSOR: Ultragenyx Pharmaceutical Inc; CRITERIA: Inclusion Criteria: 1. Must be 18 years to 70 years of age. 2. Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures. 3. Must have a documented diagnosis, confirmed by genetic testing, of hereditary inclusion body myopathy (HIBM), also known as distal myopathy, rimmed vacuoles (DMRV), or Nonaka myopathy due to demonstrated mutations in gene encoding the GNE/MNK enzyme. 4. Willing and able to comply with all study procedures, including multiple overnight stays at a hospital unit or Phase 1 unit. 5. Sexually active subjects must be willing to use an acceptable method of contraception (i.e double barrier method)while participating in the study and for 30 days after receiving the last dose of SA-ER. 6. Females of childbearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had bilateral tubal ligation at least 1 year prior to screening, or who have had total hysterectomy. Exclusion Criteria: 1. Pregnant or breastfeeding at screening or planning to become pregnant (self or partner) at any time during the study. 2. Use of any investigational product or investigational medical device within 30 days prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments. 3. Ingestion of ManNAc, sialic acid, or related metabolites or sialic acid donors that provide this substrate in either chemical or nutritional supplement form during the 30 days prior to screening. If ManNAc or other substrate was used more than 30 days prior to screening, the time period of use, the compound used, and the dose and dose regimen should be recorded in the patient's history. If a patient has been on substrate replacement therapy in the past, the investigator must consider the potential confounding effects of this therapy before enrolling the patient. 4. Presence of a condition the severity and acuity of which, in the opinion of the investigator, warrant immediate surgical intervention or other treatment. 5. Presence or history of any hypersensitivity to SA or its excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects. 6. Presence of a concurrent disease or condition that would interfere with study participation or affect safety such as swallowing difficulties. 7. Presence or history of any condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study. 8. Serum transaminase (ALT, AST, GGT) levels > 3 x upper limit of normal (ULN) or serum creatinine > 2.0 mg/dL. ; PRIMARY OUTCOME: Evaluate the safety of repeated doses of Sialic Acid - Extended Release (SA-ER) tablets in patients with HIBM; SECONDARY OUTCOME 1: Evaluate the pharmacokinetics of SA-ER after single and repeated dosing.

Yes