New hope for rare blood disorder: experimental pill reduces need for transfusions

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

* INCLUSION CRITERIA: To be eligible to participate in this study, an individual must meet all of the following criteria: 1. Diamond-Blackfan anemia defined as chronic anemia presenting on or before the third year of life, associated with reticulocytopenia and greatly reduced or absent bone marrow erythroid precursors, supported by, but not requiring either: 1. familial history 2. gene mutation testing demonstrating a known disease-causing mutation or a mutation of disease-associated gene in combination with clinical characteristics of DBA Patients with late-onset DBA (diagnosed after the third year of life) may also be included if (but only if) gene mutation testing confirms a disease-causing mutation, as above. 2. Clinically-significant anemia as defined as either: 1. hemoglobin less than 9.0 g/dL 2. red cell transfusion of at least 2 units PRBC for adults in the eight weeks prior to study enrollment 3. Relapsed and/or steroid-refractory disease or patient intolerance of systemic corticosteroids 4. Age \>= 18 years at the time of consent Although all patients without a molecular diagnosis (i.e., genetic testing positive for a disease- causing lesion) will undergo targeted gene panel testing for mutations in all known genes associated with DBA , the diagnosis of DBA is a clinical one, and as such, consent and enrollment does not require results from these genetic tests in the absence of any features that would suggest an alternative diagnosis (e.g., Fanconi Anemia, Dyskeratosis Congenita, etc.). EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: 1. Treatment with androgens (danazol or oxymetholone) or corticosteroids less than 4 weeks prior to initiating bitopertin. -Stable physiologic dose steroid replacement for adrenal insufficiency or other similar conditions is not an exclusion criterium. 2. Hypersensitivity to bitopertin or its components 3. Patient Health Questionnaire-8 (PHQ-8) score greater than or equal to 10 or imminent suicidal risk identified by the Columbia-Suicide Severity Rating Scale (C-SSRS) as defined as suicidal ideation with intent (grade 4 or 5) within the last year or any suicidal behavior within the last five years 4. Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient s ability to tolerate protocol therapy 5. Life expectancy of less than 3 months from any cause 6. History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease, including any of the following: * Recent myocardial infarction (within last 6 months), * Uncontrolled congestive heart failure, * Unstable angina (within last 6 months), * Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or third-degree AV block without a pacemaker.) * Long QT syndrome, family history of idiopathic sudden death, congenital long QT syndrome or additional risk factors for cardiac repolarization abnormality, as determined by the investigator * Impaired cardiac function such as corrected QTc\>450msec using Fridericia correction on the screening ECG, other clinically significant cardio-vascular disease (e.g., uncontrolled hypertension, history of labile hypertension), history of known structural abnormalities (e.g. cardiomyopathy). 7. Known active or uncontrolled infections not adequately responding to appropriate therapy. * Note, HIV infection is not exclusive of trial participation if the infection is effectively controlled with medications not known to interfere with bitopertin metabolism or be metabolized by pathways known to be altered by bitopertin. HIV RNA viral load must be undetectable at the time of enrollment, and CD4 cell count must be \>= 200/microL. Patients must remain on antiretroviral therapy throughout study participation and must be periodically monitored for suppression of viral load and CD4 cell count. * If drug-drug interactions between antiretroviral (e.g. HIV), antiviral (e.g., hepatitis), or antifungal medications and bitopertin are suspected (such as lopinavir, ritonavir or other strong CYP3A4 inhibitors), these must be addressed by a qualified clinical pharmacist or pharmacologist, and any changes to antiretroviral therapy need to be approved in consultation with an Infectious Disease and/or HIV specialist prior to enrollment. 8. Evidence for MDS or AML as defined by WHO criteria, or any active malignancy or likelihood of recurrence of malignancies within 12 months 9. Patients who have received chemotherapeutic treatment or other specific antineoplastic drugs or radiation therapy within 6 months of study entry 10. Female subjects who are nursing or pregnant (positive serum or urine beta-human chorionic gonadotrophin (beta-hCG) pregnancy test) at screening/baseline visit 11. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, not using highly effective methods of contraception during dosing and for 30 days after the last dose of bitopertin. Highly effective contraception methods include: * Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post- ovulation methods) and withdrawal are not acceptable methods of contraception * Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment * Male sterilization (at least 6 months prior to screening). For female patients on the study the vasectomized male partner should be the sole partner for that patient. * Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception. * In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. -Women are considered post-menopausal and not of childbearing potential if they have had over 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile age appropriate (e.g., generally 40-59 years), history of vasomotor symptoms (e.g., hot flushes) in the absence of other medical justification or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment should she be considered not of childbearing potential. * Sexually active males unless they use a condom during intercourse while taking the study treatment and for 30 days after stopping study treatment and should not father a child in this period. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the drug via seminal fluid. 12. Active alcohol/drug abuse. 13. Unable to understand the investigational nature of the study or give informed consent and does not have a legally authorized representative or surrogate that can provide informed consent. 14. Unable to take the oral study drug. 15. Concurrent participation in an investigational study within 30 days prior to enrollment or within 5-half-lives of the study drug, whichever is longer. Note: parallel enrollment in a disease registry is permitted.