Phase IIA Open Label Study to Evaluate Efficacy and Safety of BL-8040 Followed by (hATG), Cyclosporine and Methyprednisolone in Adult Subjects With Aplastic Anemia or Hypoplastic Myelodysplastic Syndrome

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02462252
• Date of registration: 25/05/2015
• Prospective Registration: Yes
• Primary sponsor: BioLineRx, Ltd.
• Public title: Phase IIA Open Label Study to Evaluate Efficacy and Safety of BL-8040 Followed by (hATG), Cyclosporine and Methyprednisolone in Adult Subjects With Aplastic Anemia or Hypoplastic Myelodysplastic Syndrome
• Scientific title: A Phase IIA, Open-label Study Designed to Evaluate Efficacy and Safety of BL-8040 Followed by Anti-Thymocyte Globulin (hATG), Cyclosporine and Methylprednisolone in Adult Subjects With Aplastic Anemia (AA) or Hypoplastic Myelodysplastic Syndrome (MDS)
• Date of first enrolment: October 2015
• Target sample size: 25
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT02462252
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Sheri Rivera

• Name: Anne Goren, B.Sc.Pharm

• Name: Tapan Kadia, MD
• Affiliation: M.D. Anderson Cancer Center

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Adult men and women aged 18 and older

2. Patient must have the ability to understand the requirements of the study and provide
informed consent.

3. Patients with the diagnosis of severe AA, who are not currently candidates for an
allogeneic stem cell transplant, fulfilling the following criteria:

1. BM cellularity < 30% and

2. Peripheral blood (PB) showing at least two of the following criteria:

Absolute neutrophil count (ANC) < 0.5 k/µL Platelet count < 30 k/µL Absolute
reticulocyte count < 60,000/µL

4. Patients with recurrent/relapsed AA will be eligible for the trial as long as they
were not previously refractory to hATG-based therapy and the relapse occurred > 3
months after response.

5. Patients with Hypoplastic MDS defined as MDS with marrow cellularity of:

- < 30% for patients < 60 years,

- < 20% for patients = 60yrs.

6. Patients must have been off of cytotoxic, immunosuppressive (except steroids), or
targeted therapy, including standard and investigational treatments for AA, for at
least 1 week or 5 half-lives whichever comes later, prior to entering this study, and
have recovered from the toxic effects of that therapy to Grade 1 or less.

7. Adequate organ function as defined below:

• Liver function:

a. Total bilirubin < 2.0 mg/dL (34 µmol/L) b. AST and/or ALT <3 x ULN

- Kidney function: creatinine < 2.5 x ULN.

8. ECOG performance status of = 2.

9. Women of childbearing potential and all men must agree to use an approved form of
contraception (e.g. oral, transdermal patch, implanted contraceptives, intrauterine
device, diaphragm, condom, abstinence or surgical sterility) prior to study entry and
for the duration of study participation through 30 days after the last dose of the
last treatment drug. Pregnancy testing is not required for post-menopausal or
surgically sterilized women.

10. Subject is able and willing to comply with the requirements of the protocol.

11. Subject or a legal guardian is able to voluntarily provide written informed consent.

Exclusion Criteria:

- 1. Known allergy or hypersensitivity to any of the test compounds, materials or
contraindication to test product.

2. Patients who have had any major surgical procedure within 14 days of Day 1. BM
biopsy is not considered a major surgical procedure.

3. Pregnant women are excluded from this study because the agents used in this study
have the potential for teratogenic or abortifacient effects. Because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with these agents, breastfeeding should be discontinued if the
mother is being treated on this trial.

4. Seropositive for HIV antibodies (HIV1 and HIV2), Hepatitis C antibody (Hep C Ab) or
a Hepatitis B carrier (positive for Hepatitis B surface antigen [HBsAg]).

5. Life expectancy of = 2 months. 6. Subjects with a clinically significant or
unstable medical or surgical condition or any other condition that cannot be
well-controlled by the allowed medications permitted in the study protocol that would
preclude safe and complete study participation, as determined by medical history,
physical examinations, ECG, laboratory tests or chest X-ray. Such conditions may
include:

• Unstable cardiovascular conditions at Baseline including but not limited to:

- Symptomatic ischemia, or

- Uncontrolled clinically significant conduction abnormalities (e.g., ventricular
tachycardia on antiarrhythmic agents are excluded; 1st degree atrioventricular
(AV) block or asymptomatic left anterior fascicular block/right bundle branch
block (LAFB/RBBB) will not be excluded); or

- Congestive heart failure (CHF) NYHA Class = 3, or

- Myocardial infarction (MI) within 3 months. • Presence of active, uncontrolled
infection. • Known central nervous system illness (e.g., Alzheimer's disease).

- A gastrointestinal disorder that may affect the absorption of study
medication.

- Use of alcohol or drug use that may interfere with the patient's ability to
participate in the study.

- Unstable psychiatric disorder that would render the patient unable to comply
with study requirements.

- Any malignancies in the 3 years prior to Baseline, excluding basal cell
carcinoma, in situ malignancy, low-risk prostate cancer, cervical cancer
after curative therapy.

- A co-morbid condition that, in the Investigator's opinion, renders the
subject at high risk for treatment complications.

7. Unable to comply with study requirements in the opinion of the
Investigator.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Aplastic Anemia

Hypoplastic Myelodysplastic Syndrome

Intervention(s)

Drug: BL-8040

Drug: Methylprednisolone

Drug: Cyclosporine

Drug: horse anti-thymocyte globulin (hATG)

Primary Outcome(s)

Response Rate [Time Frame: up to 6 months (180 days)]

Secondary Outcome(s)

Overall survival [Time Frame: up to 5 years]

Time to response [Time Frame: up to 5 years]

Change in blood product requirements compared to Baseline [Time Frame: up to 6 months (180 days)]

tolerability [Time Frame: up to end of end of study treatment (180 days)]

Toxicity [Time Frame: study treatment duration (180 days) plus 30 days following last dose of last treatment]

general safety [Time Frame: up to end of study treatment (180 days)]

Response duration [Time Frame: up to 5 years]

Secondary ID(s)

BL-8040.06

Source(s) of Monetary Support

Please refer to primary and secondary sponsors