A Phase 2/3 Study in Adult and Pediatric 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, 65+ 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, Therapy, Efficacy, Safety, 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.
Part C: To assess the PK of single and MD of osivelotor in pediatric participants with SCD.

Secondary objectives 3

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 PD properties of multiple dose osivelotor administration.
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 VOCs, measures of hemolysis, health-related quality of life assessments, neurocognitive function, and total Hb. To evaluate the safety and tolerability of 48 weeks of daily osivelotor administration.
3. Part C: To evaluate the safety and change in total Hb and clinical measures of hemolysis after multiple doses of osivelotor.

Conditions and MedDRA coding

Sickle Cell Disease

Regulatory references

Scientific advice from competent authorities

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 6

1. Part B/C 1. Participant with SCD. Documentation of SCD genotype HbSS or HbSB, may be based on history of laboratory testing or must be confirmed by laboratory testing during Screening.
2. Part B 2. Age 12 years and older, inclusive at Screening. Participants age 12 to < 18 years will only be enrolled after evaluation of safety in this age cohort in Part C Cohort C1.
3. Part B 3. More than or equal to 2 and ≤ 10 VOCs, within 12 months of Screening.
4. Part B 4./C 3. Hb ≥ 5.5 and ≤ 10.5 g/dL during Screening and considered stable by the Investigator.
5. Part B 5./C 4. For participants taking hydroxyurea and/or L-glutamine, the dose must be stable for at least 90 days prior to signing the Informed Consent Document or Assent and with no anticipated need for dose adjustments during the study in the opinion of the Investigator and no sign of hematological toxicity.
6. Part C 2. Age by cohort at Screening: a. Cohort C1: 12 to < 18 years; b. Cohort C2: 6 to < 12 years; c. Cohort C3: 2 to < 6 years; d. Cohort C4: 6 months to < 2 years

Exclusion criteria 6

1. Part B 1. / C2. Female participant who is breastfeeding or pregnant.
2. Part B 2./C 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.
3. Part B 3./ C 4. Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the Informed Consent Document.
4. Part B 4./ C5. Screening laboratory test of ALT > 4 × ULN for age.
5. Part B 5./ C 6. Acute illness or clinically significant bacterial, fungal, parasitic, or viral infection which requires therapy, including acute bacterial infection requiring antibiotics within 14 days prior to the study drug administration.
6. Part C 1. More than 10 VOCs within 12 months of Screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Part A: Change from baseline in Hb through Week 12.
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. See Section 8.1 for the definition of VOC.
3. Part C: • AUC0-last and AUC0-inf of osivelotor in whole blood and plasma after single dose, and AUC0-24 after multiple dose administration of osivelotor. • Cmax after a single dose, and both Cmax and Cmin after multiple dose administration. • Accumulation ratios based on Cmax and AUC0-24. • % Hb occupancy after multiple dose administration of osivelotor.

Secondary endpoints 3

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 LDH through Week 12. • Incidence of TEAEs, changes in laboratory assessments, ECGs, and vital signs. • Effect on Hb OEC as measured by p50 through Week 12. • AUC, Cmax, Tmax, B:P ratios of these PK parameters after the first dose. Cmin and B:P ratio after multiple dose administration. • % Hb occupancy
2. 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. • Change from baseline in PROMIS SF Pain Interference 8a raw total score at Week 48.
3. Part C: • Incidence of adverse events, changes in laboratory assessments, ECGs, and vital signs. • Change from baseline in Hb at MD Week 2 (Day 14). • Change from baseline in hemolysis measures, including indirect bilirubin, absolute and % reticulocytes, and LDH at MD Week 2 (Day 14). • RBC count at MD Week 2 (Day 14). • PK parameters after single dose in both plasma and whole blood, including t1/2, Tmax, CL/F, V/F, and B:P ratios. • PK parameters after multiple doses in both plasma and whole

Investigational products

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

Test 2

Placebo 2

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 Trials.gov Call Centre

Public contact point

Organisation

Global Blood Therapeutics Inc.

Contact name

Clinical Trials.gov Call Centre

Third parties 5

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

Application history

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