A Phase 1/2 Study to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of HMB-001 in Glanzmann Thrombasthenia

Overview

About this study

The purpose of this study is to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of HMB-001 in Participants with Glanzmann Thrombasthenia.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Part A Inclusion Criteria:

1. Age 18 to 65 years, at the time of signing informed consent.

2. Glanzmann thrombasthenia; documented abnormal, diagnostic platelet aggregometry plus
deficiency of the ?IIb?3 (GPIIb/GPIIIa) receptor via flow cytometry; or genetic
diagnosis.

3. Has not received a COVID-19 vaccine dose in the last 28 days. Has not received any
live vaccine within 4 weeks of enrollment and is not planning to have a live vaccine
during the study period.

4. Agrees not to receive COVID-19 vaccination throughout the dosing period and for 4
weeks after the final dose.

5. Has the ability to provide informed consent.

6. Has an understanding, ability, and willingness to fully comply with trial procedures
and restrictions.

7. Vital signs are within the following ranges at Screening:

1. Supine heart rate ≤ 105 bpm (after at least 5 minutes of supine rest).

2. Blood pressure (BP): Supine BP (after at least 5 minutes of supine rest or based
on 24 hours monitor demonstrating normotensive BP): i. Systolic blood pressure:
90 - 140 mmHg. ii. Diastolic blood pressure: 40 - 90 mmHg.

8. Women of child-bearing potential have a negative serum pregnancy test within 72 hours
prior to the first dose of study drug.

9. Women of child-bearing potential agree to use highly effective contraceptive methods
(excluding estrogen-containing combined oral contraceptive pill) as per exclusion
criteria and avoid egg donation for 14 days prior to Day 1, during the study
treatment, and for 6 months after the last dose of study drug.

10. Men of child-producing potential agree to use highly effective contraceptive methods
and avoid sperm donation for 14 days prior to Day 1, during the study treatment, and
for 6 months after the last dose of study drug.

11. Participants must meet the following baseline organ function, indicated by laboratory
criteria:

1. Evidence of no greater than mild to moderate reduction in renal function (stage
3a kidney disease), measured by an estimated glomerular filtration rate (eGFR) of
≥ 45 ml/min/1.73m2 at Screening

2. An aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total
bilirubin ≤ 1.5 upper limit of normal (ULN) range at Screening. For participants
with a history of Gilbert's Syndrome, total bilirubin ≤ 2 × ULN at Screening

3. Hemoglobin > 85 g/L and platelet count > 150 x 10^9/L at Screening.

Part B Inclusion Criteria:

1. Has the ability to provide informed consent, and has an understanding, ability, and
willingness to fully comply with clinical trial procedures and restrictions.

2. Age 18 to 65 years.

3. Glanzmann thrombasthenia; Genetic diagnosis is required. Abnormal, diagnostic platelet
aggregometry plus deficiency of the ?IIb?3 (GPIIb/GPIIIa) receptor via flow cytometry
should be recorded if available.

4. Patients should experience bleeding symptoms associated with Glanzmann Thrombasthenia
defined as approximately two bleeding events per week of any severity and any type and
at least one spontaneous or traumatic bleed that requires a prescribed treatment,
medical or surgical procedure within the last 12 months.

5. Has not received a COVID-19 vaccine dose in the last 28 days. Has not received any
live vaccine within 4 weeks of enrollment and is not planning to have a live vaccine
during the study period.

6. Vital signs are within the following ranges at Screening:

1. Supine heart rate ≤ 105 bpm (after at least 5 minutes of supine rest)

2. BP: Supine BP (after at least 5 minutes of supine rest or based on 24 hours
monitor demonstrating normotensive BP): i. Systolic blood pressure: 90 - 140
mmHg; ii. Diastolic blood pressure: 40 - 90 mmHg.

7. Women of child-bearing potential have a negative serum pregnancy test within 72 hours
prior to the first dose of study drug.

8. Women of child-bearing potential agree to use a highly effective contraceptive method
and to avoid egg donation for 14 days prior to Day 1, during the study treatment, and
for 6 months after the last dose of study drug. If utilizing an oral contraceptive,
women must be on a stable dose of a non-estrogen-containing formulation for at least 8
weeks prior to the start of the Run-in Observation Period and for 8 weeks after the
last dose of study drug.

9. Men of child-producing potential agree to use highly effective contraceptive methods
and avoid sperm donation for 14 days prior to Day 1, during the study treatment, and
for 6 months after the last dose of study drug.

10. Participants must meet the following baseline organ function, indicated by laboratory
criteria:

1. Evidence of no greater than mild to moderate reduction in renal function (stage
3a kidney disease), measured by an eGFR of ≥ 45 ml/min/1.73m2 at Screening.

2. An AST, ALT, and total bilirubin ≤1.5 ULN range at Screening. For participants
with a history of Gilbert's Syndrome, total bilirubin ≤ 2 × ULN at Screening.

3. Hemoglobin > 85 g/L and platelet count >120 x 10^9/L at Screening.

Part A Exclusion Criteria

1. Severe infection or inflammation at the time of Screening.

2. History of clinically significant hypersensitivity associated with monoclonal antibody
therapies.

3. Personal history of venous or arterial thrombosis or thromboembolic disease, with the
exception of catheter-associated, mild thrombophlebitis events.

4. Known severe congenital or acquired thrombophilia.

5. Has a positive test for Hepatitis B surface antigen (HbsAg), Hepatitis C antibody (HCV
Ab), or human immunodeficiency virus antibody (HIV Ab) at Screening with RNA level
above the lower limit of detection. Participants with a positive test for HCV Ab may
be included if they have a negative RNA test, consistent with cleared infection.
Participants with an HIV RNA level lower than the limit of detection may be included.

6. Is positive for COVID-19 based on lateral flow or Polymerase chain reaction (PCR)
within 48 hours prior to the first dose or had a known COVID-19 infection confirmed by
lateral flow or PCR within 6 weeks prior to the first dose of study drug.

7. Other conditions that substantially increase risk of thrombosis by the discretion of
the investigator including, but not limited to: significant family history, body mass
index (BMI) > 30 kg/m2 (moderately obese, adjusted for ethnicity), reduced mobility,
active malignancy, major surgery within 6 weeks preceding first dose of study drug,
post-partum within 12 weeks preceding first dose of study drug.

8. Women who are using estrogen-containing medication or hormone modulators (within 8
weeks pre-dose to 8 weeks post-dose of study drug).

9. Clinically significant cardiovascular disease.

10. Other conditions that substantially increase the risk of cardiovascular events by the
discretion of the Investigator including, but not limited to: smoking, cocaine use,
and uncontrolled hypertension.

11. Congenital or acquired bleeding disorders other than Glanzmann thrombasthenia.

12. Concurrent disease, treatment, medication, or abnormality in clinical laboratory tests
that may pose additional risk.

13. Addiction or other diseases that prevent the participant from appropriately assessing
the nature and scope of the clinical study or participating in study procedures.

14. Received investigational medication in another clinical study within 5 half-lives
before administration of study drug.

15. Female participants who are pregnant or breastfeeding.

Part B Exclusion Criteria

1. Active severe infection or inflammation at the time of Screening or prior to the first
dose of study drug.

2. History of clinically significant hypersensitivity associated with monoclonal antibody
therapies.

3. Personal history of venous or arterial thrombosis or thromboembolic disease, with the
exception of catheter-associated, mild thrombophlebitis events.

4. Has known, documented, high risk congenital thrombophilia.

5. Family history of unprovoked venous thrombosis in first degree relative.

6. Has a positive test for Hepatitis B surface antigen (HbsAg), Hepatitis C antibody (HCV
Ab), or human immunodeficiency virus antibody (HIV Ab) at Screening with RNA level
above the lower limit of detection. Participants with a positive test for HCV Ab may
be included if they have a negative RNA test, consistent with cleared infection.
Participants with an HIV RNA level lower than the limit of detection may be included.

7. Other conditions that substantially increase risk of thrombosis by the discretion of
the investigator including, but not limited to: BMI > 30 kg/m2 (moderately obese,
adjusted for ethnicity), reduced mobility, active malignancy major surgery within 6
weeks preceding first dose of study drug, post-partum within 12 weeks preceding first
dose of study drug.

8. Women who are using estrogen-containing medication or hormone modulators from 8 weeks
prior to the first dose of study drug until 8 weeks after the last dose of study drug
(see separate inclusion criterion for non-estrogen containing contraception
requirement).

9. Clinically significant cardiovascular disease.

10. Other conditions that substantially increase risk of cardiovascular events by the
discretion of the Investigator including, but not limited to: smoking tobacco
products, cocaine use, uncontrolled hypertension and untreated hyperlipidemia.

11. Congenital or acquired bleeding disorders other than Glanzmann thrombasthenia.

12. Concurrent disease, treatment, medication, or abnormality in clinical laboratory tests
that may pose additional risk.

13. Addiction or other diseases that prevent the participant from appropriately assessing
the nature and scope of the clinical study or participating in study procedures.

14. Received investigational medication in another clinical study within 5 half-lives
before administration of study drug.

15. Female participants who are breastfeeding.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 3/5/2024. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Rajiv Pruthi, M.B.B.S.

Open for enrollment

Contact information:

Department of Medicine (DOM) Research Hub

(507) 266-1944

DOMRESEARCHHUB@mayo.edu

More information

Publications

Publications are currently not available
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CLS-20573091

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