| CTRI Number |
CTRI/2024/07/069743 [Registered on: 01/07/2024] Trial Registered Prospectively |
| Last Modified On: |
08/05/2026 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Other |
|
Public Title of Study
|
A Phase 2/3 Study of osivelotor in Adult and Pediatric Participants with sickle cell disease |
|
Scientific Title of Study
|
A Phase 2/3 Randomized, Multicenter Study of Osivelotor Administered Orally to Participants with Sickle Cell Disease and an Open-Label Pharmacokinetics Study in Pediatric Participants with Sickle Cell Disease |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 2023-508766-14-00 |
EudraCT |
| C5351004 (GBT021601-021) Protocol Amendment 06 dt 8-Feb-2024 |
Protocol Number |
| NCT05431088 |
ClinicalTrials.gov |
|
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
|
| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
|
| Email |
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Details of Contact Person
Scientific Query
|
| Name |
Dr Seema Pai |
| Designation |
Director- Clinical Site Operations |
| Affiliation |
Pfizer Limited |
| Address |
Global Site and Study Operations, Clinical Development and Operations, Global Product Development, Pfizer Limited, 1802/1901, The Capital, Plot No. C-70, G-Block, Bandra Kurla Complex, Bandra East
Mumbai
MAHARASHTRA
400051
India |
| Phone |
8826422322 |
| Fax |
|
| Email |
seema.pai@pfizer.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Seema Pai |
| Designation |
Director- Clinical Site Operations |
| Affiliation |
Pfizer Limited |
| Address |
Global Site and Study Operations, Clinical Development and Operations, Global Product Development, Pfizer Limited, 1802/1901, The Capital, Plot No. C-70, G-Block, Bandra Kurla Complex, Bandra East
MAHARASHTRA
400051
India |
| Phone |
8826422322 |
| Fax |
|
| Email |
seema.pai@pfizer.com |
|
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Source of Monetary or Material Support
|
| Global Blood Therapeutics, Inc. a wholly owned subsidiary of Pfizer, 181 Oyster Point Blvd. South San Francisco, CA 94080 USA |
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Primary Sponsor
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| Name |
Global Blood Therapeutics, Inc. a wholly owned subsidiary of Pfizer |
| Address |
181 Oyster Point Blvd. South San Francisco, CA 94080 USA |
| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
|
| Name |
Address |
| Pfizer Limited |
The Capital, 1802/1901, Plot No. C-70 G Block, Bandra Kurla Complex, Bandra (E), Mumbai City (India) - 400051. |
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Countries of Recruitment
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Brazil
Colombia
France
Germany
Ghana
India
Kenya
Nigeria
Oman
Saudi Arabia
Uganda
United Kingdom
United States of America
Zambia |
Sites of Study
Modification(s)
|
| No of Sites = 6 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Tulika Seth |
All India Institute Medical Sciences |
Department of Hematology, Room No. 5017, 5th Floor Teaching Block, New Delhi- 110029, India
New Delhi
DELHI |
919868397236
drtulikaseth@gmail.com |
| Dr Ashutosh Panigrahi |
All India Institute Medical Sciences, Bhubaneshwar |
Bhubaneshwar, Sijua, Patrapada, Dumduma, Bhubaneshwar, Odisha, 751019
Khordha
ORISSA |
919073349572
dr.ashupanigrahi@gmail.com |
| Dr Saroj Bala |
All India Institute of Medical Sciences, Raipur |
Gate No. 4 Great Eastern Road, Opposite Gurudwara, AIIMS Campus, Tatibandh, Raipur-492099, Chhattisgarh, India
Raipur
CHHATTISGARH |
9991423527
srj.dhankhar438@gmail.com |
| Dr Siddhesh Arun Kalantri |
Chopda Medicare and Research Centre Pvt. Ltd., Magnum Heart Institute |
3/5, Patil Lane No. 1, Laxmi Nagar, Near K.B.H. Vidyalaya, Canada Corner, Nashik-422005, Maharashtra, India
Nashik
MAHARASHTRA |
918437649501
sidkalantri@gmail.com |
| Dr Seema Bhatwadekar |
Haemato Oncology Care Centre |
Kedar, New India mill compound, Jetalpur Road, Vadodara – 390020
Vadodara
GUJARAT |
919099511709
ssbkar16@gmail.com |
| Dr Hasmukh Balar |
Nirmal Hospital Pvt Ltd |
Ring Road, Surat – 395002, Gujarat, India
Surat
GUJARAT |
919979530073
drhasmukhbalar@gmail.com |
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Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 6 |
| Name of Committee |
Approval Status |
| Institute Ethics Committee, All India Institute of Medical Sciences Raipur, Room no. 2103, 2nd Floor South Wing Medical College Complex, Gate no. 5, All India Institute of Medical Sciences, Tatibandh, GE Road, Raipur, 492099, Chhattisgarh, India. |
Approved |
| Institute Ethics Committee, Old OT Block, Room No-102, Ansari Nagar, New Delhi- 110029, India |
Approved |
| Institutional Ethics Committee, AIIMS Bhubaneswar, Sijua, Patrapada Dumduma -751019, Odisha, India |
Approved |
| Magna-Care Ethics Committee, Chopda Medicare & Research Centre Pvt. Ltd, Magnum Heart Institute, Canada Corner, Nashik, Maharashtra-422005, India |
Approved |
| Nirmal Hospital Pvt Ltd Ethics Committee, Nirmal Hospital Pvt Ltd, Ring Road, Surat, 395002, Gujarat, India |
Approved |
| PARIKH INSTITUTIONAL ETHICS COMMITTEE A-4,Bhagvati park society, Opp. Tube Company, Nr. Apollo Clinic, Old Padra Road, Vadodara,Gujarat-390020 |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: D571||Sickle-cell disease without crisis, |
|
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Osivelotor |
The study will assess the efficacy and safety of 48 weeks of the optimal dose, compared to placebo. Adult participants will receive osivelotor at 300 mg QD loading dose for 7 days followed by 150 mg QD through week 48. Participants will
receive placebo tablets for 48 weeks
|
| Comparator Agent |
Placebo for Osivelotor (PF-07940367 or GBT021601) |
Participants of the study will receive placebo tablets |
|
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Inclusion Criteria
|
| Age From |
12.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
Key Inclusion Criteria:
1. Participant with SCD ages 12 years and older, inclusive at Screening.
2. Participants with stable Hb value as judged by the Investigator.
3. For participants taking hydroxyurea and/or L-glutamine, the dose must be stable for at least 90 days prior to signing the ICF or assent and with no anticipated need for dose adjustments during the study in the opinion of the Investigator.
4. More than or equal to 2 and less than or equal to 10 VOCs within 12 months of Screening.
|
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| ExclusionCriteria |
| Details |
Key Exclusion Criteria:
1. More than 10 VOCs within 12 months of Screening.
2. Female participant who is breastfeeding or pregnant.
3. Receiving regularly scheduled RBC transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or has received an RBC or exchange transfusion for any reason within 90 days of Day 1.
4. Hospitalized for sickle cell crisis or other vaso occlusive event within 14 days of signing the ICF.
5. Screening laboratory test of alanine aminotransferase (ALT) more than 4 x upper limit of normal (ULN) for age. |
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Method of Generating Random Sequence
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Computer generated randomization |
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Method of Concealment
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On-site computer system |
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Blinding/Masking
|
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded |
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Primary Outcome
|
| Outcome |
TimePoints |
| To assess the effects of osivelotor adults 150 mg QD dose compared to placebo in adult and adolescent participants with SCD as measured by Hb response and rate of VOC events |
Hb response (increase from baseline of more than 1 g per dL) at Week 48 (based on average of Hb levels at Week 40 and Week 48). Annualized rate of VOC through end of Week 48 |
|
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Secondary Outcome
|
| Outcome |
TimePoints |
| To evaluate the effects of osivelotor (adults: 150 mg QD dose) compared to placebo on relevant clinical outcomes including time to first VOC, measures of hemolysis, healthrelated quality of life assessments, neurocognitive function, & total Hb. To evaluate the safety & tolerability of 48 weeks of daily osivelotor administration. |
Key Secondary Efficacy Endpoints:
1. Change from baseline in absolute reticulocyte count at Week 48
2. Change from baseline in PROMIS SF Fatigue 13a raw total score at Week 48.
3. Change from baseline in PROMIS SF Pain Interference 8a raw total score at Week 48.
Other Secondary Efficacy Endpoints:
1. Duration of Hb response
2. Time from randomization to first Hb increase from baseline of more than 1 g per dL.
3. Time from randomization to first VOC. |
| To evaluate the effects of osivelotor adults: 150 mg QD dose compared to placebo on relevant clinical outcomes including time to first VOC, measures of hemolysis, healthrelated quality of life assessments, neurocognitive function, & total Hb. To evaluate the safety & tolerability of 48 weeks of daily osivelotor administration. |
4. Time from randomization to prohibited or restricted medications known to affect Hb or VOC
5. Change from baseline in indirect bilirubin at Week 48.
6. Change from baseline in LDH at Week 48.
7. Change from baseline in percent reticulocyte count at Week 48
8. Change from baseline in percent RBC sickling peripheral smear at Week 48.
9. Change from baseline in PROMIS NRS Pain intensity raw score at Week 48
10. PGI-S of fatigue value & change from baseline through Week 48 |
| To evaluate the effects of osivelotor adults: 150 mg QD dose compared to placebo on relevant clinical outcomes including time to first VOC, measures of hemolysis, healthrelated quality of life assessments, neurocognitive function, & total Hb. To evaluate the safety & tolerability of 48 weeks of daily osivelotor administration |
11. PGI-C of fatigue value from baseline through Week 48
12. PGI-S of pain value & change from baseline through Week 48
13. PGI-C of pain value from baseline through Week 48
14. CGI-S of SCD value & change from baseline through Week 48
15. CGI-C of SCD value from baseline through Week 48 |
| To evaluate the effects of osivelotor adults 150 mg QD dose compared to placebo on relevant clinical outcomes including time to first VOC, measures of hemolysis, healthrelated quality of life assessments, neurocognitive function, & total Hb. To evaluate the safety & tolerability of 48 weeks of daily osivelotor administration |
16. Change from baseline through Wk 48 in the Executive abilities composite score using Dimensional Change Card Sort Test, Flanker Inhibitory Control & Attention Test, & Pattern Comparison Processing Speed Test as assessed by the NIH Toolbox Cognition Module
Safety Outcome Measures
1. Incidence of TEAEs, changes in laboratory assessments, ECGs, & vital signs
PK Outcome Measures
1. Trough plasma & blood concentrations BP concentration ratio.
2. Percent Hb occupancy at Wk 48
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Target Sample Size
|
Total Sample Size="332"
Sample Size from India="33"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2/ Phase 3 |
|
Date of First Enrollment (India)
|
12/07/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
07/03/2024 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="3"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
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Publication Details
|
N/A |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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Brief Summary
|
The purpose of this study is to evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of osivelotor.
This study is three part, multicenter, phase 2/3 study for orally administered osivelotor in participants with sickle cell disease (SCD). India is participating in Part B of the study. Part B will evaluate the efficacy of osivelotor versus placebo in adult and adolescent participants with SCD for 48 weeks. |