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    Summary
    EudraCT Number:2015-002915-14
    Sponsor's Protocol Code Number:MOR208C205
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-12-17
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - PEI
    A.2EudraCT number2015-002915-14
    A.3Full title of the trial
    A Phase II, Two-Cohort, Open-Label, Multicenter Study to Evaluate the Safety and Preliminary Efficacy of MOR00208 Combined with Idelalisib or Venetoclax in Patients with Relapsed or Refractory CLL/SLL Previously Treated with Bruton’s Tyrosine Kinase (BTK) Inhibitor.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The purpose of this study is to learn about the initial effects and safety of MOR00208, given together with idelalisib or venetoclax for treatment of Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). MOR00208 is an investigational drug - one that is not approved for use in this country. Idelalisib and venetoclax are approved in many countries including this country for treatment of CLL and in the United States for treatment of CLL/ SLL (idelalisib) and CLL (venetoclax).

    A.3.2Name or abbreviated title of the trial where available
    COSMOS
    A.4.1Sponsor's protocol code numberMOR208C205
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02639910
    A.5.4Other Identifiers
    Name:US IND NumberNumber:114,856
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorMorphoSys AG
    B.1.3.4CountryGermany
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMorphoSys AG
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMorphoSys AG
    B.5.2Functional name of contact pointClinical Program Lead Oncology
    B.5.3 Address:
    B.5.3.1Street AddressSemmelweisstr. 7
    B.5.3.2Town/ cityPlanegg
    B.5.3.3Post code82152
    B.5.3.4CountryGermany
    B.5.4Telephone number+49 8989927 26856
    B.5.6E-mailinfo@morphosys.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/14/1286
    D.3 Description of the IMP
    D.3.1Product nameMOR00208
    D.3.2Product code MOR00208
    D.3.4Pharmaceutical form Lyophilisate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTafasitamab
    D.3.9.2Current sponsor codeMOR00208
    D.3.9.4EV Substance CodeSUB91252
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Zydelig 150 mg
    D.2.1.1.2Name of the Marketing Authorisation holderGilead Sciences Ireland UC
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIDELALISIB
    D.3.9.1CAS number 870281-82-6
    D.3.9.4EV Substance CodeSUB126168
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Zydelig 100 mg
    D.2.1.1.2Name of the Marketing Authorisation holderGilead Sciences Ireland UC
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNIDELALISIB
    D.3.9.1CAS number 870281-82-6
    D.3.9.4EV Substance CodeSUB126168
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Venclyxto 10 mg film-coated tablets
    D.2.1.1.2Name of the Marketing Authorisation holderAbbVie Deutschland GmbH & Co. KG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/12/1080
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNVENETOCLAX
    D.3.9.3Other descriptive namevenetoclax
    D.3.9.4EV Substance CodeSUB176260
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Venclyxto 50 mg film-coated tablets
    D.2.1.1.2Name of the Marketing Authorisation holderAbbVie Deutschland GmbH & Co. KG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/12/1080
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNVENETOCLAX
    D.3.9.3Other descriptive namevenetoclax
    D.3.9.4EV Substance CodeSUB176260
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 6
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Venclyxto 100 mg film-coated tablets
    D.2.1.1.2Name of the Marketing Authorisation holderAbbVie Deutschland GmbH & Co. KG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/12/1080
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNVENETOCLAX
    D.3.9.3Other descriptive namevenetoclax
    D.3.9.4EV Substance CodeSUB176260
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
    E.1.1.1Medical condition in easily understood language
    Rare forms of Leukemia
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10008976
    E.1.2Term Chronic lymphocytic leukemia
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10003910
    E.1.2Term B-cell small lymphocytic lymphoma NOS
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the safety of MOR00208 combined with idelalisib or venetoclax
    E.2.2Secondary objectives of the trial
    1. To determine the quality of the response
    2. To assess the potential immunogenicity of MOR00208
    3. To assess the pharmacokinetic (PK) profile of MOR00208
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Optional Sub-Study - Collection of Biological Samples for Evaluation of CD19 Expression after MOR00208 Treatment

    The sub-study is contained within Section 15.13 (Appendix M) of the main MOR208C205 study protocol.

    Study Objectives:
    • To assess potential downregulation/loss of CD19 on peripheral B cells (CLL and normal B cells) as escape mechanism to MOR00208 treatment
    • To assess the kinetics of CD19 recovery on peripheral B cells (CLL and normal B cells) after MOR00208 treatment discontinuation, if applicable
    • To assess MOR00208 serum concentrations as supportive parameter for CD19 expression analysis
    E.3Principal inclusion criteria
    Diagnosis/Trial Population
    1. Age ≥18 years
    2. Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL):
    a) history of diagnosis of CLL or SLL that meets IWCLL diagnostic criteria (Hallek et al., 2008)
    b) histologically confirmed diagnosis of SLL by lymph node biopsy and documented within medical records
    c) indication for treatment as defined by the IWCLL guidelines (Hallek et al., 2008)
    3. Patients must have both of the following:
    a) relapsed (1) or refractory (2) disease while receiving a BTK inhibitor (e.g., ibrutinib) or intolerance of such therapy
    b) single-agent or combination therapy with a BTK inhibitor for at least one month must be the patient’s most recent prior anticancer therapy
    (1) relapsed disease is defined as progressive disease in subjects who have previously achieved a PR or CR to most recent BTK inhibitor therapy
    (2) refractory disease is defined as progressive disease in subjects who have previously not achieved a PR or CR to most recent BTK inhibitor therapy, or stable disease as best response after 12 months of receiving the most recent BTK inhibitor therapy
    4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
    5. Patients with a past medical history of autologous or allogeneic stem cell transplantation must exhibit full hematological recovery without any evidence or ongoing treatment of active graft versus host disease before enrolment into the study. Laboratory Values
    6. Patients must meet the following laboratory criteria at screening:
    •adequate bone marrow function as follows:
    a) absolute neutrophil count (ANC) ≥ 1.0 × 109/L
    b) platelet count ≥ 30 × 109/L in the absence of clinically significant evidence of bleeding
    c) Cohort B only: hemoglobin ≥ 8.0 g/dL
    • Adequate hepatic and renal function as follows:
    d) total serum bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN in cases of documented liver involvement by CLL (For patients with Gilbert’s disease, serum bilirubin up to 3 × ULN is allowed provided normal direct bilirubin.)
    e) ALT and AST ≤ 2.5 × ULN or <3 ×ULN in cases of documented liver involvement by CLL
    f) serum creatinine clearance calculated using a standard Cockcroft-Gault formula (Cockroft & Gault, 1976) must be:
    • Cohort A only: ≥ 30 mL/min
    • Cohort B only: ≥ 50 mL/min
    Other Inclusion Criteria
    7. Females of childbearing potential (FCBP; see Appendix F of the protocol) must:
    a) not be pregnant as confirmed by a negative serum pregnancy test at screening and a urine pregnancy test prior to starting study therapy
    b) refrain from breastfeeding and donating blood or oocytes during the course of the study and for 3 months after the last dose of study medication (Note: All female patients are prohibited to donate blood within the before mentioned time frame)
    c) agree to ongoing pregnancy testing during the course of the study, and until 3 months after study therapy has ended. This applies even if the patient practices complete and continued sexual abstinence
    d) commit to continued abstinence from heterosexual intercourse if it is in accordance with her lifestyle or agree to use and be able to comply with the use of highly effective contraception (see Appendix F of the protocol) without interruption during the study and for 3 months after the last dose of study medication
    e) FCBP using hormonal contraceptives should add a barrier method as a second form of contraception since it is currently unknown whether idelalisib or venetoclax may affect the effectiveness of hormonal contraceptives
    8. Males must use a highly effective method of contraception (see Appendix F of the protocol) without interruption, if the patient is sexually active with a FCBP, refrain from donating blood or sperm during the study participation and for 3 months after the last dose of study medication
    9. In the opinion of the Investigator the patients must:
    a) be able to understand, give written informed consent to, and comply with all study-related procedures, medication use, and evaluations
    b) not have a history of noncompliance in relation to medical regimens or be considered potentially unreliable and/or uncooperative
    E.4Principal exclusion criteria
    Diagnosis
    1. Patients who have:
    a) non-Hodgkin’s lymphomas other than CLL/SLL
    b) transformed CLL/SLL or Richter’s syndrome as defined by the IWCLL
    c) active and uncontrolled autoimmune cytopenia Previous and Current Treatment
    2. Patients who have received treatment with a BTK inhibitor within 5 days prior to Day 1 dosing.
    3. Patients who have, within 14 days prior to Day 1 dosing:
    a) not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma-specific therapy
    b) systemic corticosteroids in doses greater than prednisone equivalent to 20 mg/day
    c) received live vaccines.
    4. Patients who:
    a) have, in the opinion of the Investigator, not recovered sufficiently from the adverse toxic effects of prior therapies
    b) have a history of previous severe allergic reactions to prior monoclonal antibody therapy, and/or hypersensitivity to the active substances or to any of the inactive ingredients / excipients contained in the study drug formulations
    c) concurrently use other anticancer or experimental treatments
    d) were previously treated with:
    • CD19-targeted therapy (applicable for Cohort A and B)
    • Cohort A only: a PI3K inhibitor treatment (e.g., idelalisib, duvelisib)
    • Cohort B only: a BCL-2 inhibitor treatment (e.g., venetoclax)
    e) Cohort B only: has a known allergy to both xanthine oxidase inhibitors and rasburicase
    f) Cohort B only: has received strong or moderate CYP3A inhibitors or inducers within 7 days, or has consumed grapefruit, grapefruit products, Seville oranges or star fruit within 3 days prior to the first dose of venetoclax
    Patient’s Medical History
    5. Prior history of malignancies other than CLL, unless the patient has been free of the disease for ≥5 years prior to screening. Exceptions to the ≥5 year time limit include a history of the following:
    a) basal cell carcinoma of the skin
    b) squamous cell carcinoma of the skin
    c) carcinoma in situ of the cervix
    d) carcinoma in situ of the breast
    e) carcinoma in situ of the bladder
    f) incidental histological finding of prostate cancer (Tumor/Nodes/Metastasis [TNM] stage of T1a or T1b)
    6. Patients with myelodysplastic syndrome
    7. Patients with systemic diseases (e.g., cardiovascular, renal, hepatic) that would in the Investigator’s opinion preclude participation in the study or compromise the patient’s ability to give informed consent
    8. Patients with diagnosis of myocardial infarction within 6 months prior to enrolment, New York Heart Association class II or higher congestive heart failure, uncontrolled angina pectoris, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemia or significant conduction system abnormalities, in the opinion of the Investigator. (Note: Patients with stable, asymptomatic atrial fibrillation are allowed in the study provided they do not meet the other cardiac exclusion criteria)
    9. Patients who:
    a) suffered significant traumatic injury or underwent major surgery within 14 days prior to treatment start
    b) have not recovered from sequelae of traumatic injury or surgical operations until Day 1 dosing
    10. Patients with central nervous system (CNS) involvement or impairment:
    a) CNS primary or secondary malignancy in present or past medical history (unless patient has been free of the disease for ≥ 5 years prior to screening) (1)
    b) CNS, meningeal or epidural malignancies (e.g., brain metastases, known leukemic meningeosis) (1)
    (1) Note: Screening for cerebrospinal fluid (CSF)/CNS involvement is not required but may be performed at the discretion of the Investigator
    c) CNS lesions/cerebrovascular event(s) with clinically significant sequelae
    d) history or evidence of clinically significant cerebrovascular CNS that would in the Investigator’s opinion preclude participation in the study or compromise the patient’s ability to give informed consent.
    11. Patients with:
    a) chronic diarrhoea and malabsorption syndrome
    b) any evidence of ongoing systemic viral, bacterial, or fungal infection (including Pneumocystis jirovecii pneumonia and Cytomegalovirus infection)
    c) history of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis
    d) Cohort A only: ongoing inflammatory bowel disease as ulcerative colitis or Crohn’s disease
    e) Cohort A only: severe COPD, or pulmonary emphysema or drug-induced pneumonitis diagnosed in previous medical history
    12. Patients with known seropositivity for or history of active viral infection with HIV.
    13. Patients with known positive hepatitis B and/or C serology
    a) HBV: patients with positive serology for HBV. (Note: Patients positive for anti-HBc may be included if HBV DNA is not detectable, but have to be monitored in 2-month intervals via HBV DNA testing)
    b) HCV: patients with positive HCV serology unless confirmed negative for HCV-ribonucleic acid (RNA)
    E.5 End points
    E.5.1Primary end point(s)
    Incidence and severity of adverse events (AEs)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Please refer to Section 9.1 Schedule of Procedures and Assessments of the Protocol.
    E.5.2Secondary end point(s)
    1. Overall response rate (ORR): defined for Cohort A as percentage of
    patients achieving a complete response (CR), a partial response (PR) or a partial response with lymphocytosis (PRL), and for Cohort B as
    percentage of patients achieving a CR or a PR
    2. Anti-MOR00208 antibody formation
    3. Pharmacokinetic analysis for MOR00208

    E.5.2.1Timepoint(s) of evaluation of this end point
    Please refer to Section 9.1 Schedule of Procedures and Assessments of the Protocol.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA21
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Austria
    Germany
    Italy
    Poland
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the main study is defined as 5 years after the first patient was enrolled (Cycle 1, Day 1) or approximately 30 days after last patient received his last treatment, whichever comes first.

    The sub-study will be completed once the last patient in the sub-study completed the last visit, or approximately 7 months after the first visit
    of the last patient enrolled in the sub-study, whichever comes first.

    The whole study will end after the completion of both the main and sub-study.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months9
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 5
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 19
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state9
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 14
    F.4.2.2In the whole clinical trial 24
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    At the end of the study, access to MOR00208 treatment can be made available to those patients who continue to derive benefit from MOR00208 treatment.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2016-06-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-04-14
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-07-06
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