Prevention of active human cytomegalovirus (HCMV) replication by re-infection or re-activation in HCMV seropositive patients after human blood precursor cell (HBPC) transplantation
Conditions
Interventions
Product Name: AIC090027
Product Code: AIC090027
Pharmaceutical Form: Film-coated tablet
CAS Number: 917389-23-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-
Sponsors
AiCuris GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients of any ethnic group aged =18 years on the day informed consent is given 2. Seropositive for HCMV IgG antibodies as tested by the local laboratory within 1 year before transplantation (if the patient had received HCMV IgG antibody treatment, the test must have been performed =30 days after HCMV IgG antibody administration). If repeated tests were performed 1 positive HCMV test confirms the patient as HCMV IgG seropositive. 3. First allogeneic HBPC transplantation performed within 40 days before randomization for one of the following diagnoses: leukaemia, lymphoma, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, multiple myeloma, myelodysplastic and myeloproliferative disorder 4. Allogeneic human leukocyte antigen (HLA) A, B, C, DR identical related or unrelated donor bone marrow or peripheral blood progenitor cell transplant recipient using high resolution typing 5. Evidence of post transplantation engraftment (absolute neutrophil count remaining =500/mm3 for at least 3 consecutive sampling days documented by a minimum of 2 tests by the local laboratory) 6. An active HCMV replication not detectable by the HCMV standard evaluation of local laboratory (pp65 or HCMV-PCR) within 5 days before starting trial medication 7. Able to swallow tablets 8. Male patients who are surgically sterile (e.g. after vasectomy) or who must agree to use an adequate method of contraception during participation in the trial and for at least 2 complete months after the final trial visit and final examination. An adequate method of contraception is defined as sexual abstinence or single barrier method with their sexual partner. Female patients who are surgically sterile (e.g. 2 sided tubal resection or ovariectomy) or post-menopausal (defined as older than 50 years of age or who have a history of no menses for at least 24 months) or Female patients of childbearing potential who must agree to use an adequate method of contraception during participation in the trial and for at least 1 complete month after the final trial visit and final examination. An adequate method of contraception is defined as sexual abstinence, single-barrier method, adequate hormonal contraception (to have started at least 7 days prior to Screening), or an intra-uterine device (IUD) (to have been in place for at least 2 months prior to Screening) 9. Negative beta-human chorionic gonadotropin (ß-HCG) blood test for women 10. Written informed consent provided to participate in this trial. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Previous allogeneic HBPC transplantation 2. Previous anti-HCMV therapy after this allogeneic HBPC transplantation 3. Ex-vivo T-cell depletion of the graft 4. Mismatched or cord blood transplant recipient 5. Any current uncontrolled active infection 6. Current or history of end-organ HCMV disease 7. Graft versus host disease (GVHD) of Grade 2 or higher (see Section 20.2) at day of randomization 8. Existing condition of requiring supplemental oxygen at day of randomization 9. Impaired liver function indicated by alanine aminotransferase (ALT) elevation =3 x upper limit of normal (ULN) (test performed by the local laboratory) 10. Reduced renal function indicated by a creatinine of = 2 x ULN (test performed by the local laboratory) 11. Severe vomiting, diarrhea, or other gastrointestinal illness precluding the effective uptake of oral medication 12. Positive results in any of the virology tests for human immunodeficiency virus antibody (HIV-Ab), hepatitis C virus antibody (HCV-Ab) or hepatitis B surface antigen (HBsAg) (tests performed by the local laboratory) 13. Co-administration within 7 days before randomization of the CYP3A4 inducers: avasimibe, carbamazepine, phenytoin, rifampicin, and any preparations containing St. John’s wort (Hypericum perforatum) 14. Breastfeeding women 15. Current evidence for active abuse of alcohol or drugs 16. Known or suspected of not being able to comply with the trial protocol 17. Not able to communicate meaningfully with the Investigator and staff 18. Participation in investigational drug trials within the last 30 days before randomization for the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the safety and efficacy of 3 different doses of AIC090027 with matching placebo. The incidence and time to onset of “HCMV prophylaxis failed” for the prevention of an active HCMV replication within an 84-day treatment period in HCMV seropositive allogeneic HBPC transplant recipients will be compared between each treatment group versus placebo.;Secondary Objective: To compare 3 different doses of AIC090027 versus matching placebo with regard to: - the PK of AIC090027 at steady-state to establish an exposure effect relationship - investigate the effect of AIC090027 on co-administered cyclosporine, tacrolimus, sirolimus, and everolimus - the incidence and time to onset of HCMV End-Organ Disease alone. - the incidence and time to onset of systemic detectable HCMV reactivation alone - the incidence and time to onset of discontinuation of trial medication within the 84 day treatment period.;Primary end point(s): The primary endpoint of the trial is the incidence and time to onset of “HCMV prophylaxis failed” within the 84 day treatment period as prevention of an active replication in HCMV positive patients. The definition for “HCMV prophylaxis failed” is: • If the patient develops systemic detectable HCMV reactivation defined by: - Two HCMV blood samples tested positive in the local laboratory, which were drawn at separate consecutive time-points (i.e. no negative samples at any intervening time-point) and which have led to the discontinuation of the trial medication and to the initiation of treatment with an alternative HCMV anti-viral medication. - In addition, one HCMV blood sample from either of the 2 time-points that tested positive in the local laboratory must also have tested positive in the central laboratory. Or if the patient develops HCMV End-Organ Disease as defined by Ljungman et al. “Definitions of Cytomegalovirus Infection and Disease in Transplant Recipients” (Clinical Infectious Diseases 2002; 34: 1094-7) | — |
Countries
Germany
Outcome results
None listed