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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