Safety Evaluation of Intramuscular Injections of PLX-R18 in Subjects With Incomplete Hematopoietic Recovery Following Hematopoietic Cell Transplantation

• ClinicalTrials.gov Identifier: NCT03002519
• Recruitment Status: Completed
• First Posted: December 23, 2016
• Last Update Posted: January 11, 2022
• Sponsor: Pluristem Ltd.
• Information provided by (Responsible Party): Pluristem Ltd.

Tracking Information

• First Submitted Date: December 13, 2016
• First Posted Date: December 23, 2016
• Last Update Posted Date: January 11, 2022
• Actual Study Start Date: February 8, 2017
• Actual Primary Completion Date: September 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 20, 2016)

• Emergent Adverse Events (AEs) [ Time Frame: Recorded after time of consent throughout the study until the last visit (~1 year) ]
• Safety laboratory values (including immunological testing) [ Time Frame: Blood samples will be collected on each visit, through study completion (~1 year) ]
• Vital signs [ Time Frame: Will be assessed during each visit, through study completion (~1 year) ]
• ECG [ Time Frame: Will be assessed during the screening visit, before each IP treatment visit and on the 14th day of participation (visit 5). ]

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety Evaluation of Intramuscular Injections of PLX-R18 in Subjects With Incomplete Hematopoietic Recovery Following Hematopoietic Cell Transplantation
• Official Title: A Phase I Open-label Dose-escalation Study to Evaluate the Safety of Intramuscular Injections of PLX-R18 in Subjects With Incomplete Hematopoietic Recovery Following Hematopoietic Cell Transplantation
• Brief Summary: This study aims to evaluate the safety of intramuscular (IM) administration of PLX-R18 in subjects with incomplete hematopoietic recovery following HCT.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Incomplete HCT (Hematopoietic Cell Transplantation)

Intervention

Biological: PLX-R18

Intramuscular (IM) administration of PLX-R18

Study Arms

Experimental: PLX-R18

Dose Escalation- first three subjects will be enrolled in the low dose cohort, 6 subjects in the intermediate-dose cohort, and 15 subjects in the high dose cohort.

Intervention: Biological: PLX-R18

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 17, 2020): 21
• Original Estimated Enrollment (submitted: December 20, 2016): 30
• Actual Study Completion Date: October 30, 2021
• Actual Primary Completion Date: September 30, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age ≥18 years.
2. At least 3 months after HCT, either autologous or allogeneic (of any source, with any preparatory regimen, for any indication), prior to study treatment.

3. Sustained platelet count ≤50,000/µL, and/or sustained Hb ≤8 g/dL and/or sustained ANC ≤1000/mm3, attributed to graft failure as a major contributor, as evident by hypocellular bone marrow.

   Cytopenia should be confirmed by at least 2 consecutive blood counts, at least one of them within 28 days prior to treatment (higher transient levels following occasional blood product transfusions are allowed).

4. Stable donor cell chimerism in at least 3 consecutive tests prior to treatment (the most recent test should be within 28 days prior to treatment).

5. If the subject had allogeneic HCT for a malignant disease, the subject should have complete donor chimerism.

   *complete donor chimerism should be determined by the investigator per site's standards.

6. General performance status evaluated by Eastern Cooperative Oncology Group 0-2 scale.
7. Signed written informed consent.

Exclusion Criteria:

INCLUSION AND EXCLUSION CRITERIA Inclusion Criteria

Subjects must meet all of the inclusion criteria listed below to be eligible for the study:

1. Age ≥18 years.
2. At least 3 months after HCT, either autologous or allogeneic (of any source, with any preparatory regimen, for any indication), prior to study treatment.
3. Sustained platelet count ≤50,000/µL, and/or sustained Hb ≤8 g/dL and/or sustained ANC ≤1000/mm3, attributed to graft failure as a major contributor, as evident by hypocellular bone marrow.

Cytopenia should be confirmed by at least 2 consecutive blood counts, at least one of them within 28 days prior to treatment (higher transient levels following occasional blood product transfusions are allowed).

4. Stable donor cell chimerism in at least 3 consecutive tests prior to treatment (the most recent test should be within 28 days prior to treatment).

5. If the subject had allogeneic HCT for a malignant disease, the subject should have complete donor chimerism.

*complete donor chimerism should be determined by the investigator per site's standards.

6. General performance status evaluated by Eastern Cooperative Oncology Group 0-2 scale.

7. Signed written informed consent. Exclusion Criteria

1. Evidence of developing malignancy since the HCT, or any evidence of malignancy at the time of screening.
2. Current active infection requiring systemic treatment (if infection resolved but antibiotic coverage continues, patient may be included).
3. Acute graft versus host disease (GvHD) Grade III or IV, or severe chronic GvHD at the time of screening.
4. Subject has received prophylactic treatment with donor lymphocyte infusion (DLI) within 6 months prior to treatment, or any other cell therapy within 3 months prior to treatment.
5. History of malignancy (other than the disease that required the HCT) within 2 years prior to screening (except for skin basal cell carcinoma or squamous cell carcinoma lesions that were fully resected with no need for further treatment, and not located at the injection site).
6. History of significant transfusion reaction including: Transfusion related acute lung injury (pulmonary edema), shock, severe disturbances of liver function tests, renal dysfunction, or hemolytic anemia (as part of the transfusion reaction).
7. Known allergies to any of the following: dimethyl sulfoxide (DMSO), human serum albumin, bovine serum albumin, gentamicin, or antihistamine.
8. History of allergic/hypersensitivity reaction to any substance having required hospitalization and/or treatment with intra-venous steroids/epinephrine or in the opinion of the Investigator the subject is at high risk of developing severe allergic/hypersensitivity reactions (does not apply to transfusion reactions - see exclusion criterion 8).
9. A known history of allergic/hypersensitivity reactions to 3 or more allergens.
10. History of uncontrolled asthma (Global Initiative for Asthma Grade III IV).
11. History of severe atopic disease (including but not limited to chronic urticaria, allergic reaction with respiratory symptoms requiring systemic steroids).
12. Medical history of human immunodeficiency virus or syphilis infection.
13. Known active hepatitis B or hepatitis C infection at the time of screening.

14. A pregnant or lactating woman or a woman who plans to become pregnant during the study. In addition, any woman of childbearing potential (not sterile or postmenopausal), who is unwilling to adhere to the use of a highly effective contraception method for the duration of the study:

    1. Oral/intravaginal/transdermal combined estrogen and progestogen containing hormonal contraception for at least 3 months prior to screening.
    2. Oral/injectable/implantable progestogen-only hormonal contraception for at least 3 months prior to screening.
    3. An intrauterine device (IUD) or intrauterine hormone-releasing system (IUS).
15. Subjects on renal replacement therapy or with estimated glomerular filtration rate (eGFR) <15 mL/min/1.73m2 (based on Modification of Diet in Renal Disease [MDRD] equation).
16. Serum glutamic pyruvic transaminase (alanine aminotransferase), serum oxaloacetic pyruvic transaminase (aspartate aminotransferase) >2.5 x upper limit of normal range.
17. International normalized ratio (INR) >2 or subjects who are on oral anticoagulant therapy with INR >2 unless anticoagulation treatment can be safely interrupted/discontinued around each investigational product (IP) treatment upon primary care physician and/or Investigator's discretion.
18. Severe or uncontrolled/unstable cardiac, pulmonary, or renal disease, including myocardial infarction or cerebrovascular accident within 3 months prior to treatment.
19. History of solid organ transplantation.
20. Signs and symptoms of active central nervous system disease.
21. Life expectancy <6 months as assessed by the Investigator.
22. Subject has participated in a clinical interventional study and received the last treatment within 30 days prior to screening.
23. In the opinion of the Investigator, the subject is unsuitable for participating in the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel, United States

Administrative Information

• NCT Number: NCT03002519
• Other Study ID Numbers: PLX-R18-HCT-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pluristem Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Pluristem Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Pluristem Ltd.
• Verification Date: January 2022