A Phase 2/3 Study in Adult and Adolescent Participants with SCD

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Global Blood Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2024-07-25

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2023-508766-14-00

WHO UTN

U1111-1306-4414

ClinicalTrials.gov

NCT05431088

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Safety, Therapy, Pharmacokinetic

Part A: To assess the effects of osivelotor in adult participants with SCD as measured by change in Hb.
Part B: 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.
OLE: To evaluate the long-term safety of osivelotor in participants with SCD.

Secondary objectives 4

1. 1. Part A: To evaluate the effects of osivelotor on Hb and clinical measures of hemolysis. To evaluate the safety and tolerability as well as the PK and pharmacodynamic (PD) properties of multiple dose osivelotor administration.
2. 2. Part B: 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, health-related quality of life assessments, and total Hb. To evaluate the safety and tolerability of 48 weeks of daily osivelotor administration.
3. 3. OLE: To evaluate long-term safety including the frequency of SCD-related complications.
4. 4. To evaluate the effects of long-term use of osivelotor on hemolytic anemia

Conditions and MedDRA coding

Sickle Cell Disease

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003241-PIP01-22

Plan to share IPD

Yes

IPD plan description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Part A&B: Participant with SCD. Documentation of SCD genotype homozygous for sickle cell allele (HbSS) or double heterozygote for sickle hemoglobin (HbS) and β-0 thalassemia (HbSB) may be based on history of laboratory testing or must be confirmed by laboratory testing during Screening.
2. 2. Part A&B: Hb ≥ 5.5 and ≤ 10.5 g/dL during Screening and considered stable by the Investigator.
3. 3. Part A&B: For participants taking hydroxyurea (HU) 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. 4. Part A&B: Female participants of child-bearing potential must agree to use a highly effective method of contraception or practice abstinence from study start to 120 days (for Part A participants) or 84 days (for Part B participants) after the last dose of study drug.
5. 5. Part A&B: Female participants of child-bearing potential must have a negative pregnancy test before administration of study drug.
6. 6. Additional Part A: Age 18 to ≤65 years, inclusive at Screening.
7. 7. Additional Part B: Age 12 years and older, inclusive at Screening.
8. 8. Additional Part B: More than or equal to 2 and ≤ 10 VOCs within 12 months of Screening.

Exclusion criteria 5

1. 1. Part A&B: More than 10 VOCs within 12 months of Screening.
2. 2. Part A&B: Female participant who is breastfeeding or pregnant.
3. 3. Part A&B: 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. 4. Part A&B: Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF.
5. 5. Part A&B: Screening laboratory test of alanine aminotransferase (ALT) > 4 × upper limit of normal (ULN) for age.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. 1. Part A: Change from baseline in Hb through Week 12.
2. 2. Part B: Co-primary endpoints • Hb response (increase from baseline of > 1 g/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.
3. 3. OLE: • Incidence of Treatment Emergent Adverse Events (TEAEs) • Incidence of serious adverse events (SAEs) • Incidence of AEs leading to discontinuation • Change from baseline in laboratory parameters.

Secondary endpoints 5

1. 1. Part A: • Hb response at Week 12 (increase from baseline of >1 g/dL). • Change from baseline in hemolysis measures, including indirect bilirubin, absolute and % reticulocytes, and lactate dehydrogenase (LDH) through Week 12. • Incidence of treatment-emergent adverse events (TEAE), changes in laboratory assessments, ECGs, and vital signs.
2. 2. Part A: • Effect on Hb oxygen equilibrium curves (OECs) as measured by p50 through Week 12. • AUC, Cmax, time of maximum concentration (Tmax), blood to plasma (B:P) ratios of these PK parameters (except Tmax) after the first dose. Cmin and B:P ratio after multiple dose administration. • % Hb occupancy through Week 12.
3. 3. Part B: Key Secondary Efficacy Endpoints: • Change from baseline in absolute reticulocyte count at Week 48 • Change from baseline in PROMIS SF Fatigue 13a raw total score at Week 48 among adult participants. • Change from baseline in PROMIS SF Pain Interference 8a raw total score at Week 48 among adult participants.
4. 4. OLE: • Annualized rate of VOC. • Incidence of SCD-related AEs.
5. 5. • Change from baseline in markers of hemolysis (hemoglobin, absolute reticulocyte count, lactate dehydrogenase, indirect bilirubin). • Hb response over time (increase from baseline of >1 g/dL).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Global Blood Therapeutics Inc.

Sponsor organisation

Global Blood Therapeutics Inc.

Address

181 Oyster Point Boulevard

City

South San Francisco

Postcode

94080-2044

Country

United States

Scientific contact point

Organisation

Global Blood Therapeutics Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Global Blood Therapeutics Inc.

Contact name

Maria-Gabriella

Third parties 6

Locations

2 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications