B5201003 Open-Label Extension

Principal Investigator: Anupam Verma
Keywords: Rivipansel , Sickle , Cell , Anemia , Vasoocclusive , GMI-1070 Department: Pediatric Administration
IRB Number: 00084335 Co Investigator:  
Specialty: Pediatric Hematology and Oncology
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Kolenya  Holly
kolenya.holly@hsc.utah.edu
(801)734-0165

Brief Summary

To evaluate the safety profile of rivipansel based on adverse events when used to treat one or more episode(s) of VOC (vaso-occlusive crises).

Inclusion Criteria

1. Completion of Study B5201002. All adverse events from Study B5201002, or their
sequelae, must have resolved or stabilized to an acceptable level, in the opinion of the
investigator and the sponsor.


2. Evidence of a personally signed and dated informed consent (and assent, where
applicable) document indicating that the subject (or a legally acceptable
representative/parent(s)/legal guardian) has been informed of all pertinent aspects of
the study.


3. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and
other study procedures.


4. Male subjects able to father children and female subjects of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study (starting from Day 35 Post-Discharge Follow-Up visit of Study B5201002/Study Entry Screening
visit of Study B5201003 to the End of Study/Early Termination visit) or for at least
28 days after the last dose of rivipansel, whichever is longer.


Female subjects who meet at least one of the following criteria will not be considered
of childbearing potential:

  • Have undergone a documented hysterectomy and/or bilateral ophorectomy;
  • Have medically confirmed ovarian failure; or
  • Have achieved post-menopausal status, defined as: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state.

All other female subjects (including females with tubal ligations and females that do
NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian
failure) will be considered to be of childbearing potential.

For pediatric female subjects:

Subjects who, in the opinion of the investigator, are biologically capable
of having children and are sexually active, must agree to use a highly effective method of
contraception consistently and correctly for the duration of the study (from Day 35
Post-Discharge Follow-Up visit of Study B5201002/Study Entry Screening visit of
Study B5201003 to the End of Study/Early Termination visit). In addition, subjects that
achieve menarche and become sexually active during this study must agree to use a highly
effective method of contraception consistently and correctly for the remainder of their
participation in the study. The investigator or his/her designee, in consultation with the
subject, will confirm the subject has selected the most appropriate method of contraception
for the individual subject and their partner from the permitted list of contraception methods
(see below), and instruct the subject in its consistent and correct use. Subjects need to affirm
that they meet at least one of the selected methods of contraception. The investigator or
his/her designee will discuss with the subject the need to use highly effective contraception
consistently and correctly according to the Schedule of Activities (Table 1 and Table 2) and
document such conversation in the subject’s chart. In addition, the investigator or his/her
designee will instruct the subject to call immediately if the selected contraception method is
discontinued or if pregnancy is known or suspected.
Highly effective methods of contraception are those that, alone or in combination, result in a
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and
include:

  • Established use of oral, inserted, injected or implanted hormonal methods of contraception provided the subject plans to remain on the same treatment throughout the entire study and has been using that hormonal contraceptive for an adequate period of time to ensure effectiveness.
  • Correctly placed copper containing intrauterine device (IUD).
  • Male condom or female condom used WITH a spermicide (ie, foam, gel, film, cream, suppository). For countries where spermicide is not available or condom plus spermicide is not accepted as highly effective contraception, this option is not appropriate.
  • Male sterilization with absence of sperm in the post-vasectomy ejaculate.
  • Bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusive procedure (provided that occlusion has been confirmed in accordance with the device’s label).

Treatment Inclusion Criteria
Subjects will be evaluated at the time of each VOC. Subjects must meet the following
criteria to receive rivipansel for treatment of the VOC:


5. Diagnosis of VOC necessitating IV opioids and admission to the hospital.
6. Able to start the first dose of rivipansel within 24 hours from administration of the
first dose of IV opioids for this hospitalization.

Exclusion Criteria

Subjects presenting at time of study entry with any of the following will not be included in
the study:
1. Non-compliance with study procedures in the double blind study (B5201002) which,
in the opinion of the Investigator, makes it likely that the subject would not comply
fully with study-related procedures in this study.

2. Occurrence of any adverse event or any cutaneous manifestation or during participation in Study B5201002 that, in the opinion of the
investigator or the adjudication committee (if relevant data have been reviewed), was
related to study drug and which would therefore make it inappropriate for the subject
to receive rivipansel in the current study.

3. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration or may interfere with the interpretation of study results and, in the
judgment of the investigator, would make the subject inappropriate for entry into this
study.

  •  Participation of a subject who experienced a clinically significant deterioration in renal function in Study B5201002 should be considered on a case by case basis by the investigator.

4. Any condition(s) that compromises the subject’s ability to comply with and/or
perform study-related activities or that poses a clinical contraindication to study
participation.

5. Participation in other studies, except Study B5201002, involving investigational
drug(s) (Phases 1-4) within 4 weeks before the current study begins and/or during
study participation.

6. Expectation that the subject will not be able to be followed for the duration of the
study.

7. Pregnant female subjects, or breastfeeding female subjects.

8. Male subjects able to father children and female subjects of childbearing potential and
at risk for pregnancy who are unwilling or unable to use a highly effective method of
contraception as outlined in this protocol for the duration of the study (starting from
Day 35 Post-Discharge Follow-Up visit for Study B5201002/Study Entry Screening
visit for Study B5201003 [depending on time of subject entry into Study B5201003]
and continuing to the End of Study/Early Termination visit) or for at least 28 days
after the last dose of rivipansel, whichever is longer.


9. Subjects who are investigational site staff members directly involved in the conduct
of the study and their family members, site staff members otherwise supervised by the
investigator, or subjects who are Pfizer employees directly involved in the conduct of
the study.


10. Active use of illicit drugs and/or alcohol dependence, as determined by the
investigator.

Treatment Exclusion Criteria
Subjects will be evaluated at the time of each VOC. Subjects presenting with any of the
following will not receive rivipansel for the VOC:

11. Treatment with rivipansel within 35 days before planned first dose of rivipansel for
current episode of VOC.

12. Occurrence of any severe and/or generalized cutaneous manifestation or any other
adverse event during participation in the current study that, in the opinion of the
investigator or the adjudication committee (if relevant data have been reviewed), was
related to study drug and which would therefore make it inappropriate for the subject
to continue to receive rivipansel in the current study.


13. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study drug administration or
may interfere with the interpretation of study results and, in the judgment of the
Investigator, would make the subject inappropriate for treatment on the study for this
episode of VOC.


14. Serious systemic infection, evidenced by clinical signs and symptoms, and/or
microbiological investigations, consistent with this diagnosis. Subjects with fever
<39C (102.2F) at the time of the decision to admit to the hospital may be
considered for enrollment if in the opinion of the investigator there is no evidence of
any serious systemic infection.


15. The following clinical risk factors of acute chest syndrome:
 Hypoxia – defined as O2 saturation of <90% (by pulse oximetry) on room air on
2 separate readings 15 minutes apart, or single value of PaO2 <60 mmHg on
arterial blood gas,
and/or
 Hemoglobin <5 gm/dL


16. Acute chest syndrome, at the time of presentation for this VOC event, as defined by
National Institutes of Health (NIH) treatment guidelines:24,25
New pulmonary infiltrate involving at least one complete lung segment consistent
with the presence of alveolar consolidation, (excluding atelectasis) AND one or more
of the following:
 Chest pain;
 Temperature >38.5C;
 Tachypnea;
 Wheezing or rales;
 Cough.


17. SCD pain atypical of VOC, including hepatic or splenic sequestration, cholecystitis, or pneumonia.

18. At the time of presentation for this VOC event:
 acute stroke
or
 severe avascular necrosis of the hip/shoulder when the presenting pain is only
in the affected hip/shoulder.


19. Estimated glomerular filtration rate (eGFR) 60 mL/min/1.73 m2 (refer to
Appendix 1 for calculation).


20. History consistent with rapidly progressive decrease or decrement in renal function,
in the opinion of the investigator (refer to Section 7.1.4.1).


21. Alanine aminotransferase (ALT/SGPT) >3xULN (based on clinic laboratory normal
range).


22. Platelets <50,000/mm3.


23. Recent (within the past 30 days) major surgery (see definition in Section 4.3.2),
hospitalization for reasons other than VOC, documented serious infection requiring
IV antibiotic treatment, or significant bleeding.


24. Recent (within the past 14 days) diagnosis of cerebrovascular accident or transient
ischemic attack.


25. Pregnant female subjects or breastfeeding female subjects.


26. Male subjects able to father children and female subjects of childbearing potential and
at risk for pregnancy who are unwilling or unable to use a highly effective method of
contraception as outlined in this protocol for the duration of the study (starting from
Day 35 Post-Discharge Follow-Up visit for Study B5201002/Study Entry Screening
visit for Study B5201003 [depending on the time of subject entry into the Study
B5201003] and continuing to the End of Study/Early Termination visit) or for at least
28 days after the last dose of rivipansel, whichever is longer.