CC-4047-MMM-001

Celgene Corporation

86 Morris Avenue, Summit, NJ, United States, 07901

Clinical Trial Disclosure 86 Morris Avenue Summit, NJ 07901, Celgene Corporation 86 Morris Avenue Summit, NJ 07901, 1 866-260-1599, ClinicalTrialDisclosure@Celgene.com

Robert Gale, MD 86 Morris Avenue Summit, NJ 07901, Robert Gale, MD Celgene Corporation 86 Morris Avenue Summit, NJ 07901, RGale@Celgene.com

No

No

No

Final

13 Nov 2014

Yes

24 Sep 2013

Yes

24 Sep 2013

No

To select a treatment regimen of CC-4047 either as single-agent or in combination with prednisone to study further in subjects with myelofibrosis with myeloid metaplasia (MMM).

Protection of Subjects by Institutional Review Board/Independent Ethics Committee Review and Approval; Protection of Patient Confidentiality

19 Apr 2007

No

Yes

Spain: 3

Austria: 5

Italy: 28

United States: 52

88

36

0

0

0

0

0

0

35

52

1

Overall Study (overall period)

Randomised - controlled

A double-blind technique was used and was chosen to minimize bias on the part of participants, investigators, and the sponsor. Identical placebo capsules were supplied to match the 0.5 mg and 1.0 mg pomalidomide capsules. Placebo to match prednisone was also provided. The blind was not to be broken during the Double-Blind Treatment Phase unless in the opinion of the investigator it was absolutely needed to safely treat the subject. The medical monitor was to be contacted prior to unblinding.

Yes

Prednisone

H02 AB07

Deltasone; Orasone

Capsule, hard

Oral use

Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study.

Pomalidomide Placebo

Placebo

Capsule, hard

Oral use

Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study.

Pomalidomide

CC-4047

Imnovid; Pomalyst

Capsule, hard

Oral use

Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal

Prednisone Placebo

Placebo

Capsule, hard

Oral use

Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal.

Pomalidomide

CC-4047

Imnovid; Pomalyst

Capsule, hard

Oral use

Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Period Title: Overall Study

Prednisone

H02 AB07

Tablet

Oral use

Oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal

Pomalidomide

CC-4047

Imnovid

Capsule, hard

Oral use

Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. Period Title: Overall Study

Predisone

H02 AB07

Tablet

Oral use

Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal.

Prednisone

Pomalidomide 2 mg

Pomalidomide 2 mg + Prednisone

Pomalidomide 0.5 mg + Prednisone

Prednisone

Pomalidomide 2 mg

Pomalidomide 2 mg + Prednisone

Pomalidomide 0.5 mg + Prednisone

A clinical responder was defined as either: a. A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or b. A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or c. A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at > 5 cm and became not palpable. Participants who discontinued the study early without achieving clinical response were counted as non-responders. Modified intent-to-treat (MITT), defined as the patients who had a confirmed diagnosis of Myelofibrosis with myeloid metaplasia (MMM), received at least one dose of study drug, and participated in the study for at least 56 days.

Primary

Up to 168 days

Statistical Analysis 1 for Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment

Prednisone v Pomalidomide 2 mg

37

Pre-specified

Participants With a Clinical Response Within the First 6 Cycles of Treatment

Prednisone v Pomalidomide 2 mg + Prednisone

39

Pre-specified

Participants With a Clinical Response Within the First 6 Cycles of Treatment

Prednisone v Pomalidomide 0.5 mg + Prednisone

41

Pre-specified

A clinical responder was defined as either: a. A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or b. A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or c. A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at > 5 cm and became not palpable. Participants who discontinued the study early without achieving clinical response were counted as non-responders. Intent-to-treat (ITT), defined as all patients who were randomized, independent of whether they received study treatment or not.

Secondary

Up to 336 days

Title: Time to the First Clinical Response Description: The time to the first clinical response achieved within 168 days after the first study drug dosing date was calculated for participants who achieved a clinical response as: Start date of the first clinical response - the first study drug date +1. A clinical responder was defined as either: a. A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or b. A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or c. A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at > 5 cm and became not palpable. Intent-to-treat population with a clinical response

Secondary

Up to 168 days

For RBC-transfusion-dependent patients, duration of response was calculated as the last day of response - first day of response +1, where the last day of response was the date of the first RBC-transfusion administered at or more than 56 days after the response started. For patients who did not receive a subsequent transfusion after the response started, the end date of response was censored at the day of last hemoglobin assessment. For RBC-transfusion-independent patients, the duration of response was calculated as the last day of response - first day of response +1, where the last day of response was the earlier of the date of a hemoglobin increase of < 2.0 g/dL and the date of a RBC transfusion at ≥ 56 days after the response started. For patients whose hemoglobin measurements were always ≥ 2.0 g/dL and never received a RBC transfusion after response started, the end date of the response was censored at the date of last hemoglobin measurement. Kaplan-Meier methodology was used.

Secondary

Up to 40 months

The FACT-An comprises the four subscales of the 27-item FACT-General Scale (FACT-G), Physical Well-being, Social/Family Well-being, Emotion Well-being, Functional Well-Being, and the Additional Concerns Anemia subscale. Questions are rated on a scale from 0 to 4, where higher scores indicate more impact on quality of life. • Physical Well-being consists of 7 questions, the subscale score ranges from 0-28; • Social/Family Well-being consists of 7 questions, the subscale score ranges from 0-28; • Emotion Well-being consists of 6 questions, the subscale score ranges from 0-24; • Functional Well-Being consists of 7 questions, the subscale score ranges from 0-28; • Anemia subscale consists of 20 questions, the subscale score ranges from 0-80; • Total FACT-An score ranges from 0-188. Intent-to-treat patients with available data.

Secondary

Baseline and Cycle 6 (168 days).

Change from Baseline in hemoglobin for participants with a clinical response within the first 6 cycles of treatment. Intent-to-treat participants with a clinical response and available hemoglobin values at each time point.

Secondary

Baseline, Cycle 6 (168 days)

Change from Baseline in hemoglobin for participants without a clinical response within the first 6 cycles of treatment. Intent-to-treat participants with no clinical response and available hemoglobin values at each time point.

Secondary

Baseline, Cycle 6 (168 days)

Participants rated abdominal discomfort or pain over the previous week on a scale from zero to ten, where zero is no discomfort or pain and ten is the worst pain imaginable. Intent-to-treat patients with available data.

Secondary

Baseline and Cycle 6 (168 days)

A serious AE (SAE) was defined as any AE which resulted in death or was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or constituted an important medical event (events that may have jeopardized the patient or required intervention to prevent one of the outcomes listed above). The severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) or according to the following scale: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Death. The Investigator determined the relationship between study drug and the occurrence of an AE as "Not Related" or "Related" (since the study was double-blinded, a patient receiving only prednisone could have an AE that was judged as related to pomalidomide, and vice-versa). Safety population (all treated patients).

Secondary

From date of the first dose of the study drug until discontinuation or the data cut-off date (up to approximately 45 months).

Percentage of participants who achieved a clinical response, presented by participants with positive janus kinase 2 (JAK2) V617F mutation results at Baseline. Includes Intent-to-treat population with non-missing JAK2 Baseline assessment results. The number of participants analyzed indicates the number of participants with a positive JAK2 result for each treatment group respectively.

Secondary

Up to 336 days

Percentage of participants who achieved a clinical response, presented by participants with negative janus kinase 2 (JAK2) V617F mutation results at Baseline. Includes Intent-to-treat population with non-missing JAK2 Baseline assessment results. The number of participants analyzed indicates the number of participants with a negative JAK2 result for each treatment group respectively.

Secondary

Up to 336 days

From the first dose of the study drug through to 30 days after the last dose; up to the data cut-off date of 18 December 2013; up to 81 months

15.0

Prednisone

Pomalidomide 2 mg

Pomalidomide 2 mg + Prednisone

Pomalidomide 0.5 mg + Prednisone