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A Dose Escalation, Dose Expansion Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-575, in Subjects With Advanced Tumors. (MEDI-575)

3. April 2018 aktualisiert von: MedImmune LLC

A Phase 1, Multicenter, Open-label, Single-arm, Dose-escalation Study to Evaluate the Safety, Tolerability, and Antitumor Activity of MEDI-575, a Fully Human Monoclonal Antibody Directed Against Platelet-derived Growth Factor Receptor Alpha (PDGFRα), in Subjects With Advanced Solid Tumors Refractory to Standard Therapy or for Which No Standard Therapy Exists

Evaluate the safety, tolerability and the tolerated maximum dose of MEDI-575 in adult subjects with advanced solid tumors refractory to standard therapy or for which no standard therapy exists.

Studienübersicht

Status

Abgeschlossen

Bedingungen

Intervention / Behandlung

Studientyp

Interventionell

Einschreibung (Tatsächlich)

49

Phase

  • Phase 1

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

  • Vereinigte Staaten
    • Colorado
      • Denver, Colorado, Vereinigte Staaten
        • Research Site
    • Indiana
      • Indianapolis, Indiana, Vereinigte Staaten
        • Research Site
    • Nevada
      • Las Vegas, Nevada, Vereinigte Staaten
        • Research Site
    • Texas
      • Dallas, Texas, Vereinigte Staaten
        • Research Site
    • Virginia
      • Norfolk, Virginia, Vereinigte Staaten
        • Research Site

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

Inclusion Criteria:

  • Histologically confirmed advanced solid tumor for which no curative or standard therapies exist
  • Karnofsky performance status of ≥ 60
  • Life expectancy of >12 weeks
  • Adequate hematologic and organ function
  • Negative serum pregnancy test (women only)
  • Two methods of birth control for female participants of child-bearing potential or male participants with their female partners of child-bearing potential

Exclusion Criteria:

  • Prior chemotherapy or investigational treatment within 4 weeks of study drug administration
  • Prior biological or immunological treatment within 6 weeks of study drug administration
  • Concurrent therapy for of cancer
  • Major surgery within four weeks or minor surgery within two weeks of study drug administration
  • History of diabetes or current treatment for diabetes
  • New York Heart Association ≥ Grade 2 congestive heart failure
  • History of myocardial infarction, unstable angina, transient ischemic attack or stroke within the previous 6 months prior to study entry
  • History of other invasive malignancy within 5 years (exceptions are cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that are surgically cured)
  • Significant active infection
  • Known brain metastases
  • Pregnancy or lactation or plans to become pregnant while on study
  • Clinically significant abnormality on ECG

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: N / A
  • Interventionsmodell: Einzelgruppenzuweisung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: MEDI-575, 3.0 mg/kg QWk Escalation Phase (Cohort 1)
Single lead-in dose of MEDI-575 at 0.5 mg/kg as a 60-minute intravenous (IV) infusion administered 7 days prior to first dose at 3.0 mg/kg; MEDI-575 administered at 3.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (once every 7 days [QWk]) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Arzneimittel: MEDI-575
MEDI-575 as an IV infusion
Experimental: MEDI-575, 6.0 mg/kg QWk Escalation Phase (Cohort 2)
MEDI-575 administered at 6.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Arzneimittel: MEDI-575
MEDI-575 as an IV infusion
Experimental: MEDI-575, 9.0 mg/kg QWk Escalation Phase (Cohort 3)
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Arzneimittel: MEDI-575
MEDI-575 as an IV infusion
Experimental: MEDI-575, 12 mg/kg QWk Escalation Phase (Cohort 4)
MEDI-575 administered at 12.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Arzneimittel: MEDI-575
MEDI-575 as an IV infusion
Experimental: MEDI-575, 15 mg/kg QWk Escalation Phase (Cohort 5)
MEDI-575 administered at 15.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Arzneimittel: MEDI-575
MEDI-575 as an IV infusion
Experimental: MEDI-575, 25 mg/kg Q3Wk Escalation Phase (Cohort 6)
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (once every 21 days [Q3Wk]) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Arzneimittel: MEDI-575
MEDI-575 as an IV infusion
Experimental: MEDI-575, 35 mg/kg Q3Wk Escalation Phase (Cohort 7)
MEDI-575 administered at 35.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Arzneimittel: MEDI-575
MEDI-575 as an IV infusion
Experimental: MEDI-575, 9.0 mg/kg QWk Expansion Phase
MEDI-575 administered at 9.0 mg/kg as a 60-minute IV infusion on Study Days 1, 8, and 15 (QWk) of each 21-day treatment cycle until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Arzneimittel: MEDI-575
MEDI-575 as an IV infusion
Experimental: MEDI-575, 25 mg/kg Q3Wk Expansion Phase
MEDI-575 administered at 25.0 mg/kg as a 90-minute IV infusion on Study Day 1 of each 21-day treatment cycle (Q3Wk) until unacceptable toxicity, documentation of disease progression, or other reasons for participant withdrawal occurred.
Arzneimittel: MEDI-575
MEDI-575 as an IV infusion

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Number of Participants With Adverse Events
Zeitfenster: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
An adverse event (AE) is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Treatment-emergent AEs (TEAEs) are events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug, for the period extending to 30 days after the last dose of study drug. Participants were counted only once for each event and by the highest event severity, regardless of how many events the participant experienced. The AEs were summarized using Medical Dictionary for Regulatory Activities (MedDRA) version 14.1.
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Number of Participants With Serious Adverse Events
Zeitfenster: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
A serious AE (SAE) is any AE that results in death, is immediately life threatening, require (or prolong) inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly or birth defect, or is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above. Treatment-emergent SAEs that emerged after start of study drug were reported. Participants were counted only once for each event and by the highest event severity, regardless of how many events the participant experienced. The SAEs were summarized using MedDRA version 14.1.
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Treatment-emergent Adverse Events Related to Laboratory Parameters
Zeitfenster: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Laboratory evaluations of blood and urine samples were performed, including hematology (complete blood count, differential, and platelet count); serum chemistry (SrChem) aspartate transaminase (AST), alanine transaminase, total bilirubin, creatinine, alkaline phosphatase, sodium, potassium, chloride, phosphorus, calcium, glucose, magnesium, albumin, and lactate dehydrogenase); and routine urinalysis. Number of participants with TEAEs related to laboratory evaluations were reported.
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations
Zeitfenster: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
All 12-lead electrocardiograms (ECGs) performed during the study were obtained in triplicate (ie, 3 ECGs were obtained within a 5-minute time interval) and analyzed. ECG parameters included heart rate (high and low), QT interval, QTcB (corrected QT interval per Bazett's formula), and QTcF (corrected QT interval per Fridericia's formula). Number of participants with TEAEs related to ECG after the start of study drug were reported.
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Treatment-emergent Adverse Events Related to Vital Sign Parameters
Zeitfenster: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate) were performed throughout the study. The TEAEs related to vital signs in participants were reported.
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
Maximum Tolerated Dose (MTD)
Zeitfenster: From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks
For the dose escalation phase, a minimum of 21 evaluable participants (3 participants each in Dose Cohorts 1 through 7) were required for this study if Dose Limiting Toxicities (DLTs) do not occur. If a DLT does occur among the first 3 participants in a cohort, 3 additional participants were to be added to the cohort; 3 more participants were to be added to a cohort to determine the MTD if only 3 participants have been previously treated at that dose. The MTD is the maximum dose at which no more than 1 out of 6 participants experienced a DLT. A DLT is defined as any grade 3 or higher hematologic toxicity or any grade 3 or higher non-hematologic toxicity except grade 3 fever (in the absence of neutropenia) or grade 3 rigors/chills.
From the start of study drug administration through 30 days after last dose of MEDI-575, up to 112 weeks

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Pharmacokinetics (PK) of MEDI-575 After the First Dose: Observed Maximum Serum Concentration (Cmax)
Zeitfenster: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
The concentration of MEDI-575 quantitatively determined in serum samples using a validated electrochemiluminescence (ECL) PK assay. The Cmax after the first dose was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Time to Maximum Concentration (Tmax)
Zeitfenster: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
The time to reach maximum serum concentration after the first dose of MEDI-575 was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Dose-normalized Maximum Serum Concentration (Cmax/Dose)
Zeitfenster: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
The Cmax/dose after the first dose of MEDI-575 was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Trough Serum Concentration (Ctrough)
Zeitfenster: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
The Ctrough ie, measured concentration at the end of a dosing interval (taken directly before next dose administration) of MEDI-575 was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Area Under the Serum Concentration-time Curve Over the Dosing Interval (AUCτ)
Zeitfenster: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
The AUCτ was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
PK of MEDI-575 After the First Dose: Dose-normalized Area Under the Serum Concentration-time Curve (AUCτ/Dose)
Zeitfenster: For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
The AUCτ/dose was obtained directly from the measured concentration-time curves. The concentration-time curve is the result of blood sampling at specified time points and its measured concentration of MEDI-575.
For 0.5/3, 6, 9, 12, 15 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3 and 8 (pre-dose); For 25 and 35 mg/kg: Cycle 1: Day 1 (pre- and end of infusion, 2 and 6 hours post infusion), Days 2, 3, 8 and 15.
Number of Participants Positive for Anti-drug Antibodies Formation for MEDI-575 at Any Visit
Zeitfenster: Preinfusion on Cycle 1 Day 1 and 30 days after the last dose, up to 112 weeks
Blood samples for immunogenicity assessments were collected from participants prior to the initiation of infusion of each treatment cycle of MEDI-575. Anti-MEDI-575 antibodies were analyzed using the electro-chemiluminescence (ECL) based method. Only the number of participants positive for anti-MEDI-575 antibodies at any visit are presented.
Preinfusion on Cycle 1 Day 1 and 30 days after the last dose, up to 112 weeks
Percentage of Participants With Objective Response
Zeitfenster: From study entry through the end of the study, up to 34 months
Objective response rate is defined as the proportion of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after the initial documentation of response. The CR is defined as disappearance of all target and non-target lesions, and normalization of tumor marker level. The PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
From study entry through the end of the study, up to 34 months
Time to Response
Time to response was measured from the start of treatment with MEDI-575 to the first documentation of objective response (confirmed CR or PR). The time to response is assessed only for the participants who have achieved the objective response.
Duration of Response
Duration of response is defined as the duration from the first documentation of objective response to the first documented disease progression. Disease progression is defined according to RECIST guidelines (ie, at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions). The duration of response was censored on the date of last tumor assessment documenting absence of disease progression for participants who have no documented progression prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. Duration of response was calculated for the subgroup of participants with an objective response.
Time to Progression
Zeitfenster: Start of treatment with MEDI-575 until the documentation of disease progression, up to 24 months
Time to progression (TTP) is defined as time from the start of treatment with MEDI-575 until the documentation of disease progression. Disease progression is defined according to RECIST guidelines (ie, at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions). The TTP was censored on the date of last tumor assessment documenting absence of tumor progression for participants who have no documented progression prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. TTP was censored on the first date of treatment for the participants with no tumor assessments after the start of MEDI-575 treatment.
Start of treatment with MEDI-575 until the documentation of disease progression, up to 24 months
Progression-free Survival
Zeitfenster: Start of treatment with MEDI-575 until the documentation of disease progression or death due to any cause whichever occurs first, up to 24 months
Progression-free survival (PFS) is defined as time from the start of treatment with MEDI-575 until the documentation of disease progression or death due to any cause, whichever occurred first. Disease progression is defined according to RECIST guidelines (ie, at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions). PFS was censored on the date of last tumor assessment documenting absence of tumor progression for participants who have no documented progression and were still alive prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. PFS was censored on the first date of treatment for the participants with no tumor assessments after the start of MEDI-575 treatment.
Start of treatment with MEDI-575 until the documentation of disease progression or death due to any cause whichever occurs first, up to 24 months
Overall Survival
Zeitfenster: From the start of treatment with MEDI-575 until death or end of study, up to 33 months
Overall survival (OS) is defined as the time from the start of treatment with MEDI-575 until death. For the participants who were alive at the end of study or lost to follow-up, OS was censored on the last date when participants were known to be alive.
From the start of treatment with MEDI-575 until death or end of study, up to 33 months

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

MedImmune LLC

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Nützliche Links

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

2. März 2009

Primärer Abschluss (Tatsächlich)

19. Januar 2012

Studienabschluss (Tatsächlich)

19. Januar 2012

Studienanmeldedaten

Zuerst eingereicht

23. Dezember 2008

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

30. Dezember 2008

Zuerst gepostet (Schätzen)

1. Januar 2009

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

26. Juni 2018

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

3. April 2018

Zuletzt verifiziert

1. April 2018

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Andere Studien-ID-Nummern

  • MI-CP187

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