1.
ClinicalTrials.gov; 22/02/2022; TrialID: NCT05319587
Clinical Trial Register
| ICTRP | ID: ictrp-NCT05319587
ABSTRACT
Condition:
Leukemia, Myeloid, AcuteIntervention:
Drug: Liposomal Annamycin;Drug: CytarabinePrimary outcome:
Evaluate the safety and identify the MTD/RP2D of L-Annamycin in combination with a standard regimen of cytarabine (Ara-C, cytosine arabinoside)Criteria:
Inclusion Criteria:
1. The subject has a pathologically confirmed diagnosis of AML by World Health
Organization classification. This must be in the form of either a bone marrow aspirate
or biopsy or a CBC that demonstrates >5% myeloblasts.
2. The subject has AML and has not received prior therapy or is refractory to or relapsed
after induction therapy. To be defined as relapse, there must be >5% blasts in the
bone marrow.
3. For the expansion phase only (i.e., after the MTD/RP2D is established), subjects must
be treated with L-Annamycin as first- second- or third-line therapy (i.e., subjects
will not have received more than two prior therapies).
4. The subject is age =18 years at the time of signing informed consent.
5. The subject has received no chemotherapy, radiation, or major surgery within 2 weeks
prior to first dose of study drug and/or has recovered from the toxic side effects of
that therapy unless treatment is indicated as a result of progressive disease, such as
hydroxyurea.
6. The subject has received no investigational therapy within 4 weeks of the first dose
of study drug.
7. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to
2.
8. The subject has adequate laboratory results including the following:
1. Bilirubin =2 times the upper limit of normal unless due to Gilbert Syndrome or
leukemic infiltration of the liver.
2. Serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic
transaminase (SGPT), and alkaline phosphatase <2.5 times the upper limit of
normal unless due to organ involvement.
3. Adequate renal function with creatinine levels =2 times the upper limit of
normal.
9. The subject can understand and sign the informed consent document, can communicate
with the Investigator, and can understand and comply with the requirements of the
protocol.
10. Women of childbearing potential must have a negative serum or urine beta-human
chorionic gonadotropin test within 72 hours prior to first dose of study drug to rule
out pregnancy.
11. All men and women must agree to practice effective contraception during the entire
study period and after discontinuing study drug, unless documentation of infertility
exists.
1. Sexually active, fertile women must use 2 effective forms of contraception
(abstinence, intrauterine device, oral contraceptive, or double barrier device)
from the time of informed consent until at least 6 months after discontinuing
study drug.
2. Sexually active men and their sexual partners must use effective contraceptive
methods from the time of subject informed consent until at least 3 months after
discontinuing study drug.
Exclusion Criteria:
1. The subject was diagnosed with acute promyelocytic leukemia.
2. The subject is receiving concomitant therapy that includes other chemotherapy that is
or may be active against AML except for agents such as hydroxyurea, just to control
the WBC count until chemotherapy or prophylaxis and/or treatment of opportunistic or
other infection with antibiotics, antifungals, and/or antiviral agents, including
therapy for meningeal disease (i.e., intrathecal chemotherapy), supportive measures,
and medications as per standard of care up to Day 1 of L-Annamycin administration.
3. The subject received prior mediastinal radiotherapy.
4. The subject has central nervous system involvement.
5. The subject has any condition that, in the opinion of the Investigator, places the
subject at unacceptable risk if he/she were to participate in the study.
6. The subject has an LVEF <50%, valvular heart disease, or severe hypertension. Cardiac
subjects with a New York Heart Association classification of 3 or 4 will be excluded.
(Cardiology consultation should be requested if any question arises about cardiac
function). This also includes subjects with baseline QT/QTc interval >480 msec, a
history of additional risk factors for torsade des pointes (e.g., heart failure,
hypokalemia, family history of Long QT Syndrome), and use of concomitant medications
that significantly prolong the QT/QTc interval.
7. The subject has clinically relevant serious comorbid medical conditions including, but
not limited to, active infection, recent (less than or equal to 6 months) myocardial
infarction, unstable angina, symptomatic congestive heart failure, uncontrolled
hypertension, uncontrolled cardiac arrhythmias, chronic obstructive or chronic
restrictive pulmonary disease, known positive status for human immunodeficiency virus
and/or active hepatitis B or C, cirrhosis, or psychiatric illness/social situations
that would limit compliance with study requirements.
a. Subjects with a documented COVID diagnosis within 14 days of screening must have a
documented negative PCR test and remain asymptomatic for 14 days from that test result
before starting study medication.
8. The subject is pregnant, lactating, or not using adequate contraception.
9. The subject has a known allergy to anthracyclines and/or hypersensitivity to
cytarabine, its excipients, or to any contrast media needed for imaging required per
protocol.
10. The subject has any evidence of mucositis/stomatitis at the time of study entry or
previous history of severe (=Grade 3) mucositis from prior therapy.
11. The subject is required to use moderate or strong inhibitors and inducers of
Cytochrome P450 family of enzymes (CYP) and transporters that cannot be held for 3
days prior to Day 1 and during treatment days
2.
ClinicalTrials.gov; 29/11/2021; TrialID: NCT05195723
Clinical Trial Register
| ICTRP | ID: ictrp-NCT05195723
ABSTRACT
Condition:
Healthy VolunteerIntervention:
Drug: WP1122;Drug: PlaceboPrimary outcome:
Safety in Single Ascending Dose (SAD);Safety in Multiple Ascending Dose (MAD)Criteria:
Inclusion Criteria:
1. Subject is capable of giving written informed consent, which includes compliance with
the requirements and restrictions listed in the consent form;
2. Subject is able to understand and comply with protocol requirements, instructions, and
protocol-stated restrictions and is likely to complete the study as planned;
3. Male or female, aged 18 to 55 years (inclusive) at the time of signing the informed
consent form (ICF);
4. Subject must be willing to undergo COVID-19 testing per clinical pharmacology unit
/Phase 1 clinic guidelines;
5. Subject must complete full COVID-19 vaccination course at least 2 weeks prior to study
drug administration;
6. Minimum body weight of =50 kg (110 lbs) for men and =45 kg (99 lbs) for women. Maximum
body weight of =100 kg (220 lbs). Body Mass Index from 18 to 30 kg/m2 (values rounded
to the nearest 10th of a unit);
7. Healthy as determined by a responsible and experienced physician, based on a medical
evaluation, including medical history, physical examination, laboratory tests, and
ECG:
1. No evidence of clinically significant cardiac, pulmonary, hepatic, biliary,
gastrointestinal, or renal disorders, or cancer within the past 5 years (except
localized or in situ cancer of the skin);
2. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline
phosphatase, bilirubin, and creatinine lower than or equal to the ULN. Abnormal
values can be repeated once at the discretion of the Investigator or designee;
3. White blood cell count (including differential), hemoglobin and platelets must be
above the lower limit of normal, and if above the ULN, must not be clinically
significant in the opinion of the Investigator. A subject with laboratory values
outside the reference range may be included at the Investigator's discretion if
it is considered clinically insignificant, unlikely to introduce additional risk
factors and, in their opinion, does not interfere with study procedures;
8. Women of childbearing potential (WOCBP*) must use a highly effective form of birth
control (confirmed by the Investigator). Rhythm methods will not be considered as a
highly effective method of birth control. Highly effective forms of birth control
include:
1. Abstinence;
2. Vasectomized partner (provided that the partner is the sole sexual partner of
WOCBP and that the vasectomized partner has received medical assessment of the
surgical success);
3. Oral, intravaginal, or transdermal combined (estrogen and progestogen containing)
hormonal contraception associated with inhibition of ovulation;
4. Oral, injectable, or implantable progestogen-only hormone contraception
associated with inhibition of ovulation;
5. Any effective intrauterine device/levonorgestrel intrauterine system;
6. Female sterilization by tubal occlusion;
7. WOCBP must agree to use a highly effective method of birth control, as defined
above, from the time of signing the ICF, throughout the study duration and until
30 days after the last dose of study drug. Volunteers must have a negative serum
pregnancy test result at screening; *WOCBP are defined as women who are NOT
permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral
salpingectomy), and who are NOT post-menopausal. Women will be considered
post-menopausal if they have been amenorrhoeic for at least 12 months without an
alternative medical cause and follicle stimulating hormone (FSH) > 40 IU/mL.
9. Non-vasectomized male volunteers must use an adequate method of contraception (condom
with spermicide) from signing the ICF throughout the study duration and until 30 days
after the last dose of study drug. Male volunteers must not donate sperm from time of
signing the ICF until at least 30 days after the last dose of the study drug.
Exclusion Criteria:
1. Women who are pregnant, breastfeeding or intending to become pregnant, or men
intending to father children within the projected duration of the trial from screening
until 14 days following last dose;
2. Currently participating in or has participated in a study with an investigational
product (IP) within 30 days or 5 half-lives, whichever is longer, preceding Day -1;
3. Due to the current pandemic:
1. Evidence of current SARS-CoV-2 infection (COVID-19) based on testing at
screening;
2. Documented prior COVID-19 infection in the last 6 months;
3. Prior COVID 19 infection with ongoing sequelae (i.e., long-hauler COVID), or
history of COVID-19 infection requiring an intensive care unit stay or mechanical
ventilation;
4. Current or history of the following medical conditions:
1. Respiratory disease requiring current medical intervention;
2. Hypersensitivity or severe allergic reactions to vaccines or drugs;
3. Diagnosis of diabetes mellitus or history of hypo- or hyperglycemia;
4. Clinically relevant hypertension;
5. History or active diagnosis of renal disease secondary to diabetes, hypertension,
vascular disease;
6. History of bleeding diathesis or coagulopathy;
7. Cardiovascular diseases:
i) QTcF =430 msec; History or family history of clinically significant or unstable ECG
abnormalities (e.g., prolonged QT syndrome [torsade de pointes] or arrhythmias,
including QT prolongation due to medical treatment), sudden cardiac death at a young
age, or current use of a QT prolonging drug ii) Angina; iii) Congestive heart failure;
iv) Myocardial infarction within the previous 6 months; v) Diastolic dysfunction; vi)
Coronary artery disease; h. Malignancy within 5 years of screening (exceptions are
squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or
malignancy that in the opinion of the Investigator, with concurrence with the
Sponsor's Medical Monitor, is considered cured with minimal risk of recurrence);
5. Immunosuppression as a result of underlying illness or treatment including:
1. Primary immunodeficiencies;
2. Long-term use (=7 days) of oral or parenteral glucocorticoids;
3. Current or anticipated use of disease-modifying doses of antirheumatic drugs and
biologic disease-modifying drugs, and no use of such drugs within the last 12
months;