REP0114

Dompé Farmaceutici S.p.A.

Via Santa Lucia, 6, Milano, Italy, 20122

Clinical Trial Transparency Manager, Dompé Farmaceutici S.p.A., 39 02 583831, clinops@pec.dompe.it

Clinical Trial Transparency Manager, Dompé Farmaceutici S.p.A., 39 02 583831, clinops@pec.dompe.it

No

No

No

Final

20 Feb 2019

Yes

20 Feb 2019

Yes

23 Mar 2020

No

To evaluate Progression Free Survival (PFS), defined as the number of days between the date of randomization and the date of clinical disease progression (PD) according to RECIST criteria version 1.1, as assessed by Independent Radiology Review, or death for any cause, whichever occurs first, in patients with metastatic triple-negative breast cancer (TNBC) treated with the combination of paclitaxel and orally administered reparixin compared to paclitaxel alone.

The study was conducted in full compliance with the principles of the "Declaration of Helsinki" and subsequent revisions, International Conference on Harmonisation (ICH) guidelines, and all of the applicable US Code of Federal Regulations (CFR), 21 CFR Part 50 & 312. In addition, this study adhered to all local regulatory requirements and requirements for data protection.

29 Jul 2015

No

Yes

Poland: 9

Spain: 15

Belgium: 10

Czech Republic: 11

France: 14

Italy: 28

United States: 36

123

87

0

0

0

0

0

0

90

33

0

Overall study (overall period)

Randomised - controlled

Reparixin tablets and placebo tablets were packaged in white PVDC/PE//PVC/aluminum blisters in the form of patient kits and were numbered to maintain blinding.

Yes

Reparixin

Tablet

Oral use

1200 mg three times a day (t.i.d.) continuing from Day 1 to Day 21 of 28-day cycle.

Paclitaxel

Solution for solution for infusion

Intravenous use

80 mg/m2 intravenous (i.v.) (Days 1, 8, and 15 of 28-day cycle).

Placebo

Tablet

Oral use

1200 mg three times a day (t.i.d.) continuing from Day 1 to Day 21 of 28-day cycle..

Paclitaxel

Solution for solution for infusion

Intravenous use

80 mg/m2 intravenous (i.v.) (Days 1, 8, and 15 of 28-day cycle)

Group 1

Group 2

Group 1 - ITT population

The Intent-to-Treat (ITT) Population consisted of all patients who are randomized and was based upon the randomized treatment, regardless of the treatment actually received. Patients were in the ITT analysis whether or not they received study drug. The primary and secondary efficacy analyses were presented primarily for the ITT Population.

Group 2 - ITT population

The Intent-to-Treat (ITT) Population consisted of all patients who are randomized and was based upon the randomized treatment, regardless of the treatment actually received. Patients were in the ITT analysis whether or not they received study drug. The primary and secondary efficacy analyses were presented primarily for the ITT Population.

Group 1 - Safety population

The Safety Population consisted of all patients who had taken at least one dose of the study treatment and was based upon the treatment they actually received.

Group 2 - Safety population

The Safety Population consisted of all patients who had taken at least one dose of the study treatment and was based upon the treatment they actually received.

Group 1 - Response-Evaluable population

The Response-Evaluable Population consisted of all patients who had completed at least one cycle of treatment and had a baseline assessment and have undergone at least one post-baseline disease assessment.

Group 2 - Response-Evaluable population

The Response-Evaluable Population consisted of all patients who had completed at least one cycle of treatment and had a baseline assessment and have undergone at least one post-baseline disease assessment.

Group 1

Group 2

Group 1 - ITT population

The Intent-to-Treat (ITT) Population consisted of all patients who are randomized and was based upon the randomized treatment, regardless of the treatment actually received. Patients were in the ITT analysis whether or not they received study drug. The primary and secondary efficacy analyses were presented primarily for the ITT Population.

Group 2 - ITT population

The Intent-to-Treat (ITT) Population consisted of all patients who are randomized and was based upon the randomized treatment, regardless of the treatment actually received. Patients were in the ITT analysis whether or not they received study drug. The primary and secondary efficacy analyses were presented primarily for the ITT Population.

Group 1 - Safety population

The Safety Population consisted of all patients who had taken at least one dose of the study treatment and was based upon the treatment they actually received.

Group 2 - Safety population

The Safety Population consisted of all patients who had taken at least one dose of the study treatment and was based upon the treatment they actually received.

Group 1 - Response-Evaluable population

The Response-Evaluable Population consisted of all patients who had completed at least one cycle of treatment and had a baseline assessment and have undergone at least one post-baseline disease assessment.

Group 2 - Response-Evaluable population

The Response-Evaluable Population consisted of all patients who had completed at least one cycle of treatment and had a baseline assessment and have undergone at least one post-baseline disease assessment.

PFS was defined as the time from randomization to first documentation of disease progression, according to RECIST criteria version 1.1, as assessed by Independent Radiology Review, or to death due to any cause, whichever occurred first. Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.

Primary

Baseline up to every 8 weeks until disease progression or death, whichever occurs first.

Group 1 - ITT population v Group 2 - ITT population

123

Pre-specified

1.14

2-sided

OS was defined as the time from randomization until death due to any cause. For patients who did not die, time of death was censored at the date of last contact. Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.

Secondary

Baseline until death due to any cause.

Group 1 - ITT population v Group 2 - ITT population

123

Pre-specified

1.03

2-sided

The ORR was defined as the percentage of patients achieving CR or PR in the Evaluable Population. The response rate was calculated from the independently reviewed assessment best response. In case of PR or CR, only confirmed cases were considered to be responses. Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Patients with unknown or missing response, including response of “not all evaluated” or “unable to determine”, were treated as non-responders; i.e., they were included in the denominator when calculating the percentages. Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.

Secondary

Baseline up to every 8 weeks until documented disease progression.

Group 2 - Response-Evaluable population v Group 1 - Response-Evaluable population

111

Pre-specified

1.262

2-sided

PFS was defined as the time from randomization to first documentation of disease progression, according to RECIST criteria version 1.1, as assessed by Independent Radiology Review, or to death due to any cause, whichever occurred first. For each treatment group, the Kaplan-Meier estimates for the median PFS time, the first and third quartiles were presented, along with approximate 95% confidence intervals if there were a sufficient number of progressions or deaths. Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.

Secondary

At screening and every 8 weeks

Duration of overall response (DOR) in days for the investigator assessments is measured from the time response criteria are first met for CR or PR (whichever is first recorded on the “Disease Response” page on the CRF) until either death or the first date that recurrent or PD is objectively documented (on the “Disease Response” page on the CRF or the Follow-Up Disease Evaluation page indicates disease progression and there is supporting information in the Disease Status pages) per RECIST version 1.1. If a patient is lost to follow-up with no documentation of PD, DOR was censored at the last evaluable tumor assessment. DOR was calculated only for responding patients (PR or CR) as recorded on the CRF page “Disease Response” based upon the RECIST version 1.1. Duration of overall response was calculated only for patients with confirmed CR or PR. Patients must have completed at least 1 cycle and performed at least 1 disease assessment to be considered evaluable for response.

Secondary

Baseline up to every 8 weeks until documented disease progression.

Group 1 - Response-Evaluable population v Group 2 - Response-Evaluable population

111

Pre-specified

Treatment-emergent adverse events (TEAEs) are those which first occur or increase in severity or relationship to study drug after the first dose of study drug and before 30 days after the last dose of study treatment, reparixin/placebo. In the case of missing or partial dates, any AE that could have started on or after first dose date was assumed to be treatment-emergent. In the case of missing or partial dates, imputed dates (see section 10.1 AE date imputation) were used.

Secondary

Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days.

A serious adverse event (SAE) in human drug trials is defined as any untoward medical occurrence that at any dose 1 - results in death, (fatal) 2 - is life-threatening 3 - requires inpatient hospitalization or causes prolongation of existing hospitalization 4 - results in persistent or significant disability/incapacity, 5 - may have caused a congenital anomaly/birth defect, or 6 - requires intervention to prevent permanent impairment or damage.

Secondary

Throughout the study, until off-treatment visit.

BOR is defined as the best response among all overall responses (in the order complete response [CR], partial response [PR], stable disease [SD], and progressive disease [PD]) recorded as an independent review response from the start of reparixin or placebo until disease progression/recurrence or end of treatment, or death, whichever comes first. The status of BOR of PR or CR needs to be confirmed by repeat tumor assessment within no less than 4 weeks according to RECIST version 1.1. If the status of CR or PR cannot be confirmed by repeat tumor assessment, the best overall response of unconfirmed CR and PR will be PR and SD, respectively. Patients must have completed at least 1 cycle and performed at least 1 disease assessment to be considered evaluable for response.

Secondary

From the start of treatment, every 8 weeks.

Group 2 - Response-Evaluable population v Group 1 - Response-Evaluable population

111

Pre-specified

1.101

2-sided

Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days.

Incidence and profile of the TEAEs during the study are typical and expected for patients on chemotherapy, and was similar in both groups. The most common TEAEs in group 1 were nausea, alopecia, anemia, asthenia, and diarrhea. The most common TEAEs in group 2 were fatigue, nausea, alopecia, diarrhea, and asthenia. Here only these are reported.

20

Group 1 - Safety population

Group 2- Safety population