Study of the Efficacy and Safety of Ponsegromab in Patients With Cancer, Cachexia and Elevated GDF-15

Pfizer187 enrolled

Overview

Study to evaluate the efficacy, safety and tolerability of ponsegromab compared to placebo in patients with cancer, cachexia, and elevated GDF 15.

A 12 week double blind study to evaluate the efficacy, safety and tolerability of ponsegromab compared to placebo in patients with cancer, cachexia, and elevated GDF 15. During the initial 12-week treatment period (Part A), a total of 3 doses of ponsegromab or placebo will be administered 4 weeks apart subcutaneously. Each dose contains two injections. Part B is an optional open-label treatment period consisting of ponsegromab administered every 4 weeks subcutaneously for up to one year. Part B does not include placebo. Assessments include: * Body weight measurements * Measure the impact of ponsegromab compared to placebo on physical activity. * Measure the impact of ponsegromab compared to placebo on appetite, fatigue, nausea, vomiting and physical function questionnaires. * Blood samples to evaluate safety and additional endpoints including the amount of study drug in the blood and the effects of the study drug on levels of GDF15 * Up to 3 additional blood samples (two samples during Part A and one sample during Part B, if relevant) in a subset of participants as part of a substudy for more comprehensive assessment of the amount of study drug in the blood and of the effects of the study drug on levels of GDF-15.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

187

Conditions

Non-small Cell Lung Cancer Pancreatic Cancer Colorectal Cancer Loss of Appetite Fatigue Cachexia

Interventions

ponsegromabDRUG

Double-Blind ponsegromab Treatment followed by Open Label ponsegromab Treatment

Placebo for ponsegromabDRUG

Double-Blind placebo Treatment followed by Open Label ponsegromab Treatment

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Documented active diagnosis of non-small cell lung, pancreatic, colorectal cancer * Cachexia defined by Fearon criteria of weight loss * Serum GDF-15 concentrations * Signed informed consent * ECOG PS ≤3 with life expectancy of at least 4 months to be able to complete Part A. Key Exclusion Criteria: * Receiving tube feedings or parenteral nutrition at the time of Screening or Randomization. * Current active reversible causes of decreased food intake. * Cachexia caused by other reasons. * History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody. * inadequate liver function * renal disease requiring dialysis

Locations (78)

Outcomes

Primary Outcomes

Part A: Change From Baseline in Body Weight at Week 12

Body weight was measured in kilograms using a calibrated weighing scale. Baseline was defined as the last average of the duplicate measurements prior to, or on Day 1. The average of the duplicate body weights collected at assessment time was considered. The posterior medians and 90 percent (%) credible intervals (5th and 95th percentiles of the relevant posterior distribution) were reported for each randomized dose (including placebo). 4-Parameter maximal effect (E max) model: change from baseline = E 0 + (E max \* dose\^Hill) / (ED 50\^Hill + dose\^Hill), where E0 is the placebo effect, E max is the maximum effect, ED 50 is the dose producing 50% of the maximum effect, and Hill is the slope parameter. Model utilized a Bayesian methodology with a robustified, informative meta-analytic predictive prior for the placebo change from baseline at week 12.

Time frame: Baseline, Week 12

Secondary Outcomes

Part A: Change From Baseline in Physical Activity at Week 12

Physical activity was monitored using accelerometry (wearable digital sensors). Physical activity was categorized as: sedentary activity, non-sedentary physical activity, and moderate to vigorous physical activity. In this outcome measure time for each type of physical activity per day was considered. Baseline was defined as the mean taken over the 8 days of wear during screening. Mean taken over the 8 days of wear before Week 12 was considered. Analysis was performed using mixed models repeated measures (MMRM) model.

Time frame: Baseline, Week 12

Part A: Change From Baseline in Mean Activity Level During Maximum 6 Minutes at Week 12

Physical activity was monitored using accelerometry (wearable digital sensors). In this outcome measure mean activity level during maximum 6 minutes was considered. Baseline was defined as the mean taken over the 8 days of wear during screening. Mean taken over the 8 days of wear before Week 12 was considered. Analysis was performed using MMRM model.

Time frame: Baseline, Week 12

Part A: Change From Baseline in Total Vector Magnitude at Week 12

Data from ClinicalTrials.gov

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CARTI Conway

Conway, Arkansas, United States

CARTI Cancer Center

Little Rock, Arkansas, United States

CARTI North Little Rock

North Little Rock, Arkansas, United States

CARTI Stuttgart

Stuttgart, Arkansas, United States

Pacific Cancer Medical Center INC

Anaheim, California, United States

Beverly Hills Cancer Center

Beverly Hills, California, United States

Emad Ibrahim,MD,INC.

Redlands, California, United States

Providence Medical Foundation

Santa Rosa, California, United States

IU Health Arnett Cancer Center

Lafayette, Indiana, United States

Pennington Biomedical Research Center

Baton Rouge, Louisiana, United States

...and 68 more locations

Total vector magnitude is a measure of overall physical activity. Baseline was defined as the mean taken over the 8 days of wear during screening. Mean taken over the 8 days of wear before Week 12 was considered. Analysis was performed using MMRM model.

Time frame: Baseline, Week 12

Part A: Change From Baseline in Gait at Week 12

Gait was monitored using accelerometry (wearable digital sensors). Analysis was performed using MMRM model. Gait included: gait speed and 95th percentile of gait speed. Baseline was defined as the mean taken over the 8 days of wear during screening. Mean taken over the 8 days of wear before Week 12 was considered. Analysis was performed using MMRM model.

Time frame: Baseline, Week 12

Part A: Change From Baseline in Functional Assessment of Anorexia-Cachexia Therapy- Anorexia and Cachexia Subscale (FAACT-ACS) at Week 12

FAACT-ACS is a 12-item symptom-specific subscale to measure participants' concerns about their anorexia (appetite) or cachexia (weight) for past 7 days. Each item was scored from 0 to 4, where 0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, and 4= very much. The total FAACT-ACS score ranged from 0 to 48. Higher scores are associated with a higher health-related quality of life. FAACT-ACS was analyzed using an MMRM model.

Time frame: Baseline (prior to dose on Day 1), Week 12

Part A: Change From Baseline in FAACT- 5-Item Anorexia Symptom Scale (5IASS) at Week 12

FAACT-5IASS is a 5-item subscale to measure participants' perceptions of anorexia (appetite) concerns for past 7 days. Each item was scored from 0 to 4, where 0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, and 4= very much. The total FAACT-5IASS score ranged from 0 to 20. Higher scores are associated with a higher health-related quality of life. FAACT-5IASS was analyzed using an MMRM model.

Time frame: Baseline (prior to dose on Day 1), Week 12

Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue

The CRCSD is a daily, self-reported questionnaire that measured severity of symptoms related to cancer cachexia: appetite, nausea, vomiting, and fatigue. Participants rated appetite, nausea and physical fatigue symptom every day, and weekly averages were calculated over the 7 days prior, from 0 to 10, where 0 = no symptom and 10 = worst possible symptom. Higher scores indicated more severe disease. CRCSD was analyzed using an MMRM model.

Time frame: Baseline, Week 12

Part A: Median Change From Baseline in CRCSD Scores at Week 12: Vomiting Frequency

The CRCSD is a daily, self-reported questionnaire that measured severity of symptoms related to cancer cachexia: vomiting frequency. Participants rated vomiting frequency over the past 24 hours, from 0 to 30, where 0 = no symptom and 30 = worst possible symptom. Higher scores indicated more severe disease.

Time frame: Baseline, Week 12

Part A: Number of Participants With Treatment Emergent Adverse Events (TEAE)

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. TEAE were defined as any event that was not present before exposure to study drug, or any event already present that worsened in either intensity or frequency after exposure to study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included serious AEs and all non-SAEs.

Time frame: From start of study drug on Day 1 maximum up to 4 weeks post last dose on Week 12 (maximum up to approximately Week 16)

Part A: Number of Participants With Incidence of Laboratory Test Abnormalities

Laboratory test abnormality parameters included: hematology- hemoglobin (gram per deciliter \[g/dL\]), hematocrit (%), erythrocytes (10\^12/Liter \[L\]) less than (\<) 0.8\*lower limit of normal (LLN); platelets (10\^9/L) \<0.5\*LLN to more than (\>) 1.75\*upper limit of normal (ULN); leukocytes (10\^9/L) \<0.6\*LLN to \>1.5\*ULN; lymphocytes, neutrophils (10\^9/L) \<0.8\*LLN to \>1.2\*ULN. Clinical chemistry- bilirubin, glucose (mg/dL) \>1.5\*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (Units/L \[U/L\]) \>3.0\*ULN; protein, albumin (gram \[g\]/dL) \<0.8\*LLN; urea (mmol/L) \>1.3xULN; creatinine (mg/dL) \>1.3\*ULN; sodium (milliequivalents \[mEq\]/L) \<0.95\*LLN; potassium (mEq/L) \<0.9\*LLN to \>1.1\*ULN.

Time frame: Day 1 up to Week 12

Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria

Vital signs criteria included: supine systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg), increase and decrease in change of more than or equal to (\>=) 30mmHg; supine diastolic blood pressure (DBP) \<50 mmHg, increase and decrease in change of \>= 20mmHg; pulse rate \<40 beats per minute (bpm) to \>120 bpm. Only rows which included at least 1 participant in any reporting group with abnormality were reported in this outcome measure.

Time frame: Day 1 up to Week 12

Part A: Number of Participants With Clinically Significant Echocardiogram (ECG) Abnormalities

ECG parameters included heart rate (HR), PR interval, QT interval, QTc corrected using Fridericia's formula (QTcF) and QRS complex. HR: RR (interval between 2 successive R waves on ECG) decrease \>25% and to a VR (interval between QRS wave and T wave on ECG) \>100, RR increase \>25% and to a VR \<50; PR interval: baseline less than or equal to (\<=) 200 and % change \>= 50%; QT interval: \>450, \>480, \>500, increase from baseline \>30, increase from baseline \>60; QTcF: 470 \< value \<= 480, 480 \< value \<= 500, value \> 500, 30 \< change \<= 60 and change \>60; QRS complex: value \>= 140, % change \>=50%. Clinically significant values were determined by the investigator.

Time frame: Day 1 up to Week 12