Cachexia, a loss of weight due to the catabolism of muscle and fat tissue. The progressive worsening of cachexia impacts a cancer patient’s quality of life and contributes to poor survival. MedDRA version: 21.1 Level: LLT Classification code 10064015 Term: Cancer cachexia System Organ Class: 100000004861
Conditions
Sponsors
Pfizer Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age and Sex: 1.Participants aged =18 years (or the minimum age of consent if >18 in accordance with local regulations) at Screening who have signed informed consent. a.A female participant is eligible to participate if she is not pregnant or breastfeeding. b.Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants. Disease Characteristics: 2.Documented histologic or cytologic active diagnosis of NSCLC, PANC, or CRC and are currently receiving, or have completed, SOC treatment for this cancer (which may include systemic therapy). 3.Cachexia defined by Fearon criteria of weight loss as (See Section 8.1.1 for details if the participant’s body weight is unavailable from medical record): •BMI 2% within 6 months prior to Screening; or •involuntary weight loss of >5% within 6 months prior to screening irrespective of BMI. 4.Serum GDF-15 concentrations of =1.5 ng/mL (as measured using the Investigational Use Only Roche Elecsys GDF 15 assay)10 at Screening. 5.Participants who are assessed by the investigator to have: •an ECOG PS =3, and, •a life expectancy of at least 4 months to be able to complete Part A. Other Inclusion Criteria: 6.Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 67 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 101
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions: 1.Current active reversible causes of decreased food intake, as determined by the Investigator. These causes may include, but are not limited to: •NCI CTCAE Grade 3 or 4 oral mucositis; •NCI CTCAE Grade 3 or 4 GI disorders (nausea, vomiting, diarrhea, and constipation); •Mechanical obstructions interfering with the participant’s ability to eat. 2.Receiving tube feedings or parenteral nutrition (either total or partial) at the time of Screening or Randomization. 3.Cachexia caused by other reasons, as determined by the investigator, including, but not limited to: •Severe COPD requiring use of home O2; •NYHA class III-IV heart failure; •AIDS. 4.Undergoing major surgery (central venous access placement and tumor biopsies are not considered major surgery) within 4 weeks prior to randomization. Patient must have recovered from acute effects of surgery prior to Screening. Patient should not have plans to undergo major surgical procedures during the study. 5.Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study. 6.History of allergic or anaphylactic reaction to any therapeutic or diagnostic monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibody. Prior/Concurrent Therapy: 7.Current use of any prohibited concomitant medication(s) within 4 weeks prior to first dose of study intervention. Refer to Section 6.9. Prior/Concurrent Clinical Study Experience: 8.Concurrent administration of investigational products (including drug, biologic agents, or vaccines) are not permitted within 30 days (or as determined by the local requirement) or 5 half lives (whichever is longer) of the first dose of study intervention. Refer to Section 6.9 . 9.Enrollment and previously dosed in a prior study with ponsegromab. Diagnostic Assessments: 10.History of severe liver disease or cirrhosis, unrelated to metastatic cancer. Potential study participants with the following liver function test abnormalities will also be excluded; result may be confirmed by a single repeat test, if necessary: •Total bilirubin =1.5 × ULN (except for Gilbert’s syndrome) •AST >3 × ULN (AST > 5X ULN if there is liver involvement by the tumor) •ALT >3 × ULN (ALT >5X ULN if there is liver involvement by the tumor) •Alkaline phosphatase >3 x ULN (Alkaline phosphatase >5X ULN if there is liver involvement by the tumor and/or in case of bone metastases, or if considered related to prior surgery e.g. pancreaticoduodenectomy). 11.Renal disease requiring dialysis. Other Exclusion Criteria: 12.Current adherence to a calorie-restricted diet with the intention weight loss. 13.Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of ponsegromab compared with placebo on body weight in participants with cancer, cachexia, and elevated concentrations of GDF-15;Secondary Objective: - To evaluate the effect of ponsegromab compared to placebo on physical activity and gait as measured by wearable digital sensors in participants with cancer, cachexia, and elevated concentrations of GDF-15. - To evaluate the effect of ponsegromab compared to placebo on the appetite-related symptoms as measured by FAACT in participants with cancer, cachexia, and elevated concentrations of GDF-15. - To evaluate the effect of ponsegromab compared to placebo on anorexia/appetite nausea, vomiting, and fatigue measured by the CRCSD, Pfizer-developed instrument, in participants with cancer, cachexia, and elevated concentrations of GDF-15. - To characterize the safety and tolerability of repeated SC administrations of ponsegromab compared to placebo in participants with cancer, cachexia, and elevated concentrations of GDF-15.;Primary end point(s): Change from baseline in body weight at Week 12.;Timepoint(s) of evaluation of this end point: week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Change from baseline in physical activity and gait endpoints measured with remote digital sensors at Week 12. •Moderate to vigorous physical activity time; •Sedentary activity time; •Non sedentary activity time; •Total vector magnitude; •Mean activity level during M6min; •Mean gait speed; •95th percentile gait speed. •Change from baseline in FAACT sub scale scores at Week 12: •FAACT-ACS; •FAACT-5IASS •Change from baseline score for the questions from the CRCSD at Week 12 related to: -Anorexia/appetite; -Nausea and vomiting; - Fatigue. •Incidence of adverse events, safety laboratory tests, vital signs and ECG abnormalities;Timepoint(s) of evaluation of this end point: -week 12 - thorough the study for secondary endpoint | — |
Countries
Australia, Bulgaria, Canada, China, Czechia, France, Hungary, Japan, Poland, Slovakia, Spain, Taiwan, United States
Contacts
Public ContactClinical Trials.gov Call Centre
Pfizer Inc.
Outcome results
None listed