1L Luspa vs Esa in Ntd Low-Risk MDS Patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Celgene Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

11 Oct 2023 → ongoing

Decision date (initial)

2023-10-05

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Celgene Corporation

External identifiers

EU CT number

2022-500430-29-00

WHO UTN

U1111-1274-9158

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

To compare the proportion of participants with lower-risk NTD MDS who convert to TD (≥ 3 units/16 weeks based on IWG 2018) between luspatercept vs. epoetin
alfa.

Secondary objectives 1

1. To compare the erythroid response of luspatercept vs. epoetin alfa in participants with lower-risk NTD MDS based on IWG 2018

Conditions and MedDRA coding

Myelodysplastic Syndrome (MDS)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participant must be ≥ 18 years of age (or local age of consent) at the time of signing the informed consent
2. Participant has documented diagnosis of MDS according to World Health Organization (WHO) 2016 (Appendix 5) that meet IPSS-R classification of very low, low, or intermediate risk disease, (Intermediate-risk of ≤ 3.5 IPSS-R score) confirmed via bone marrow aspirate and: - < 5% blasts in bone marrow and < 1% blasts in peripheral blood.
3. Participant has a baseline endogenous serum erythropoietin level of ≤ 500 U/L.
4. Participant must be transfusion independent, according to IWG 2018 criteria (Appendix 15) as documented by the following criteria: - Received no RBC transfusions within 16 weeks prior to randomization. Note: RBC transfusions of 1 to 2 units within the 16 weeks prior to enrollment are allowed provided those 1-2 RBC transfusion units are administered for an acute event/illness (ie, surgical procedure, bleeding, infection) or presence of comorbidity (including cardiovascular, pulmonary, cerebrovascular), and not for the treatment of low hemoglobin (with or without symptoms) alone
5. Participant has a baseline Hb concentration prior to randomization of ≤ 9.5 g/dL. The baseline Hb will be calculated using the mean of the two lowest available Hb measurements within 16 weeks prior to randomization and must include at least one central lab Hb reading done within the screening period (no more than 35 days before randomization). Note: the two Hb measurements must have been performed at least seven days apart. Hb levels less than 21 days following RBC transfusion should not be used. Split samples for local assessments are not required.
6. Participant has symptom(s) of anemia: - Participant records a severity score of “moderate” or greater on at least 1 PGI-S item of fatigue, weakness, shortness of breath, or dizziness performed during the screening period
7. Participant has Eastern Cooperative Oncology Group score of 0, 1, or 2.
8. Participant is erythropoiesis-stimulating agent naive. Participants may be randomized at the investigator’s discretion if the participant received no more than 2 prior doses of epoetin alfa or, epoetin alfa biosimilar, or darbepoetin alfa, with the last dose at least 8 weeks prior to randomization.

Exclusion criteria 9

1. Participant with MDS associated with del(5q) cytogenetic abnormality or MDS unclassifiable (MDS-U) according to WHO 2016 classification
2. Participant with the following subtypes of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) according to WHO 2016,classification81: chronic myelomonocytic leukemia atypical chronic myeloid leukemia, BCR ABL1 negative; juvenile myelomonocytic leukemia,; or MDS/MPN unclassifiable. Note that MDS/MPN-RS-T is not an exclusion.
3. Participant with secondary MDS (ie, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases).
4. Participant with known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia (including severe G6PD deficiency, pyruvate kinase deficiency, hemoglobinopathy such as sickle cell disease, etc), or hypothyroidism, or any type of known clinically significant bleeding or sequestration, or drug-induced anemia (eg, mycophenolate). i) Iron deficiency to be determined by serum ferritin below the normal range and additional testing if clinically indicated (eg, calculated transferrin saturation [iron/total iron binding capacity ≤ 20%] or bone marrow aspirate stain for iron).
5. Bleeding disorders manifested by frequent bleeding episodes (eg, menorrhagia, epistaxis, clotting disorders)
6. Participant with known history of diagnosis of acute myeloid leukemia
7. Persistent hypertension. with systolic blood pressure of ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg or both, during the screening period despite adequate treatment, or with a history of hypertensive crisis or hypertensive encephalopathy.
8. Participant with prior history of malignancies other than MDS, unless the participant has been free of the disease for ≥ 5 years. However, participants with the following history/concurrent conditions are allowed: i) Basal or squamous cell carcinoma of the skin - Carcinoma in situ of the cervix - Carcinoma in situ of the breast - Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis clinical staging system
9. Participant with absolute neutrophil count (ANC) ≤ 500/μL (0.5 x 10^9/L) or platelet count ≤ 50,000/μL (50 x 10^9/L).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Conversion to TD (IWG 2018 defined as ≥ 3 units/16 weeks) during any continuous 16-week interval within the 96-week Treatment Period

Secondary endpoints 1

1. Achievement of an increase in mean Hb values from baseline of ≥ 1.5 g/dL in any continuous 16-week interval within the 48-week Treatment Period in the absence of transfusion

Investigational products

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

Test 2

Comparator 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Celgene Corp.

Sponsor organisation

Celgene Corp.

Address

Route 206 And Province Line Road

City

Princeton

Postcode

08543-4000

Country

United States

Scientific contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Public contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Third parties 14

Locations

8 EU/EEA countries · 51 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 124 files

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

Application history

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