A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO INVESTIGATE THE EFFICACY, SAFETY AND TOLERABILITY OF PONSEGROMAB IN PATIENTS WITH CANCER, CACHEXIA, AND ELEVATED CONCENTRATIONS OF GDF-15, FOLLOWED BY AN OPTIONAL OPEN-LABEL TREATMENT PERIOD (PROACC -1)
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Pfizer
- Enrollment
- 187
- Locations
- 146
- Primary Endpoint
- Part A: Change From Baseline in Body Weight at Week 12
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Double-blind for 12-week double-blind treatment period followed by an up to 1 year optional open-label treatment period
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
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
Arms & Interventions
Double-Blind ponsegromab Treatment low dose followed by Open Label ponsegromab Treatment
ponsegromab low dose subcutaneous injection every 4 weeks
Intervention: ponsegromab (Drug)
Double-Blind ponsegromab Treatment medium dose followed by Open Label ponsegromab Treatment
ponsegromab medium dose subcutaneous injection every 4 weeks
Intervention: ponsegromab (Drug)
Double-Blind Placebo Treatment followed by Open-Label ponsegromab Treatment
Match placebo subcutaneous injection every 4 weeks
Intervention: Placebo for ponsegromab (Drug)
Double-Blind ponsegromab Treatment high dose followed by Open Label ponsegromab Treatment
ponsegromab high dose subcutaneous injection every 4 weeks
Intervention: ponsegromab (Drug)
Outcomes
Primary Outcomes
Part A: Change From Baseline in Body Weight at Week 12
Time Frame: 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 Outcomes
- Part A: Change From Baseline in Physical Activity at Week 12(Baseline, Week 12)
- Part A: Change From Baseline in Mean Activity Level During Maximum 6 Minutes at Week 12(Baseline, Week 12)
- Part A: Change From Baseline in Total Vector Magnitude at Week 12(Baseline, Week 12)
- Part A: Change From Baseline in Gait at Week 12(Baseline, Week 12)
- 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)
- 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)
- Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue(Baseline, Week 12)
- Part A: Median Change From Baseline in CRCSD Scores at Week 12: Vomiting Frequency(Baseline, Week 12)
- 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))
- Part A: Number of Participants With Incidence of Laboratory Test Abnormalities(Day 1 up to Week 12)
- Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria(Day 1 up to Week 12)
- Part A: Number of Participants With Clinically Significant Echocardiogram (ECG) Abnormalities(Day 1 up to Week 12)
Investigators
Study Sites (146)
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