Study of the Efficacy and Safety of Ponsegromab in Patients With Cancer, Cachexia and Elevated GDF-15
- Conditions
- Non-small Cell Lung CancerLoss of AppetiteColorectal CancerCachexiaPancreatic CancerFatigue
- Interventions
- Drug: Placebo for ponsegromab
- Registration Number
- NCT05546476
- Lead Sponsor
- Pfizer
- Brief Summary
Study to evaluate the efficacy, safety and tolerability of ponsegromab compared to placebo in patients with cancer, cachexia, and elevated GDF 15.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 187
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Double-Blind ponsegromab Treatment high dose followed by Open Label ponsegromab Treatment ponsegromab ponsegromab high dose subcutaneous injection every 4 weeks Double-Blind Placebo Treatment followed by Open-Label ponsegromab Treatment Placebo for ponsegromab Match placebo subcutaneous injection every 4 weeks Double-Blind ponsegromab Treatment medium dose followed by Open Label ponsegromab Treatment ponsegromab ponsegromab medium dose subcutaneous injection every 4 weeks Double-Blind ponsegromab Treatment low dose followed by Open Label ponsegromab Treatment ponsegromab ponsegromab low dose subcutaneous injection every 4 weeks
- Primary Outcome Measures
Name Time Method Part A: Change From Baseline in Body Weight at Week 12 Baseline, 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.
- Secondary Outcome Measures
Name Time Method Part A: Change From Baseline in Physical Activity at Week 12 Baseline, 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.
Part A: Change From Baseline in Mean Activity Level During Maximum 6 Minutes at Week 12 Baseline, 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.
Part A: Change From Baseline in Total Vector Magnitude at Week 12 Baseline, Week 12 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.
Part A: Change From Baseline in Gait at Week 12 Baseline, 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.
Part A: Change From Baseline in Functional Assessment of Anorexia-Cachexia Therapy- Anorexia and Cachexia Subscale (FAACT-ACS) at Week 12 Baseline (prior to dose on Day 1), 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.
Part A: Change From Baseline in FAACT- 5-Item Anorexia Symptom Scale (5IASS) at Week 12 Baseline (prior to dose on Day 1), 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.
Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue Baseline, Week 12 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.
Part A: Median Change From Baseline in CRCSD Scores at Week 12: Vomiting Frequency Baseline, Week 12 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.
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAE) 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) 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.
Part A: Number of Participants With Incidence of Laboratory Test Abnormalities Day 1 up to Week 12 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.
Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria Day 1 up to Week 12 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.
Part A: Number of Participants With Clinically Significant Echocardiogram (ECG) Abnormalities Day 1 up to Week 12 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.
Trial Locations
- Locations (78)
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸València, Spain
Chi Mei Hospital - Liouying Branch
🇨🇳Tainan City, Tainan, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
Országos Korányi Pulmonológiai Intézet
🇭🇺Budapest, Hungary
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Complex Oncology Center - Burgas
🇧🇬Burgas, Bulgaria
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
Tandem Clinical Research
🇺🇸Marrero, Louisiana, United States
Bozeman Health Deaconess Hospital
🇺🇸Bozeman, Montana, United States
Oregon Health and Science University: Center for Health and Healing 1
🇺🇸Portland, Oregon, United States
Oregon Health and Science University: Center for Health and Healing 2
🇺🇸Portland, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Carta - Clinical Associates in Research Therapeutics of America, LLC
🇺🇸San Antonio, Texas, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Wenatchee Valley Hospital
🇺🇸Wenatchee, Washington, United States
St Vincent's Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Orange Hospital
🇦🇺Orange, New South Wales, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Western Health-Sunshine & Footscray Hospitals
🇦🇺St Albans, Victoria, Australia
Specialized Hospital for Active Treatment of Oncology - Haskovo
🇧🇬Haskovo, Bulgaria
Complex Oncology Center - Ruse EOOD
🇧🇬Ruse, Bulgaria
Complex Oncology Center - Shumen
🇧🇬Shumen, Bulgaria
Multiprofile Hospital for Active Treatment Serdika EOOD
🇧🇬Sofia, Bulgaria
MHAT for Women's Health Nadezhda
🇧🇬Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment Sofiamed
🇧🇬Sofia, Bulgaria
Complex Oncology Center - Vratsa
🇧🇬Vratsa, Bulgaria
The Ottawa Hospital - General Campus
🇨🇦Ottawa, Ontario, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
CIUSSS- saguenay-Lac-Saint-Jean
🇨🇦Chicoutimi, Quebec, Canada
Centre intégré de santé et de services sociaux du Bas Saint-Laurent- Hôpital régional de Rimouski
🇨🇦Rimouski, Quebec, Canada
Peking University First Hospital
🇨🇳Beijing, Beijing, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Changzhou No.2 People's Hospital
🇨🇳Changzhou, Jiangsu, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Qilu Hospital of Shandong University
🇨🇳Jinan, Shandong, China
Shanghai Changhai Hospital
🇨🇳Shanghai, Shanghai, China
Shanxi Provincial Cancer Hospital
🇨🇳Taiyuan, Shanxi, China
Sir Run Run Shaw Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
The 2nd Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China
Bacs-Kiskun Varmegyei Oktatokorhaz
🇭🇺Kecskemét, Bács-kiskun, Hungary
Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház
🇭🇺Szolnok, Jász-nagykun-szolnok, Hungary
Semmelweis Egyetem
🇭🇺Budapest, Hungary
National Hospital Organization Shikoku Cancer Center
🇯🇵Matsuyama, Ehime, Japan
Hyogo Cancer Center
🇯🇵Akashi, Hyogo, Japan
Kanagawa cancer center
🇯🇵Yokohama, Kanagawa, Japan
Aichi Cancer Center Hospital
🇯🇵Nagoya, Nagoya, Aichi, Japan
Shizuoka Cancer Center
🇯🇵Nagaizumi-cho, Shizuoka, Japan
University Hospital,Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Japan
Japanese Foundation for Cancer Research
🇯🇵Tokyo, Japan
Centrum Badań Klinicznych Jagiellońskie Centrum Innowacji sp. z o.o.
🇵🇱Kraków, Małopolskie, Poland
Regionalny Szpital Specjalistyczny im. Dr. Wladyslawa Bieganskiego
🇵🇱Grudziadz, Poland
NZOZ "Vegamed"
🇵🇱Katowice, Poland
Specjalistyczna Praktyka Lekarska Slawomir Mandziuk
🇵🇱Lublin, Poland
Fakultna nemocnica s poliklinikou F. D. Roosevelta Banska Bystrica
🇸🇰Banska Bystrica, Slovakia
Univerzitna nemocnica Bratislava, Nemocnica Ruzinov
🇸🇰Bratislava, Slovakia
Narodny onkologicky ustav, II. Onkologicka klinika LFUK a NOU
🇸🇰Bratislava, Slovakia
Fakultna nemocnica s poliklinikou Nove Zamky
🇸🇰Nove Zamky, Slovakia
Nemocnica na okraji mesta, n.o.
🇸🇰Partizanske, Slovakia
Fakultna nemocnica Trnava
🇸🇰Trnava, Slovakia
Hospital Universitari General de Catalunya
🇪🇸Sant Cugat del Vallès, Barcelona [barcelona], Spain
Institut Català d'Oncologia - L'Hospitalet
🇪🇸L'Hospitalet de Llobregat, Catalunya [cataluña], Spain
Hospital Son Llàtzer
🇪🇸Palma, Illes Balears [islas Baleares], Spain
Fundación Instituto Valenciano de Oncología
🇪🇸Valencia, Valenciana, Comunitat, Spain
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Chang Gung Medical Foundation-Linkou Branch
🇨🇳Taoyuan, Taiwan