Study of the Efficacy and Safety of Ponsegromab in Patients With Cancer, Cachexia and Elevated GDF-15 (PROACC-1)

• ClinicalTrials.gov Identifier: NCT05546476
• Recruitment Status: Active, not recruiting
• First Posted: September 19, 2022
• Last Update Posted: April 11, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: August 12, 2022
• First Posted Date: September 19, 2022
• Last Update Posted Date: April 11, 2024
• Actual Study Start Date: November 21, 2022
• Actual Primary Completion Date: March 13, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 15, 2022): Change from baseline in body weight for ponsegromab compared to placebo [ Time Frame: baseline, Week 12 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 30, 2022)

• Change from baseline in physical activity as measured with remote digital sensors [ Time Frame: baseline, Week 12 ]
  evaluation of physical activity (Sedentary, light and moderate) and gait speed.
• change from baseline in Functional Assessment of Anorexia-Cachexia Therapy (FAACT-ACS and FAACT-5IASS) scores [ Time Frame: baseline, Week 12 ]
  FACT-G score sums 27 items; ACS score sums 12 items; both use a 5-point scale (0-4).Higher scores are associated with a higher health-related quality of life.
• Change from baseline in anorexia/appetite; Nausea and vomiting; and Fatigue as measured by the Cancer Related Cachexia Symptom Diary (CRCSD) [ Time Frame: baseline, Week 12 ]
  Self-reported questionnaire that measures severity of symptoms related to cancer cachexia: appetite, nausea, vomiting, and fatigue.
• Incidence of adverse events [ Time Frame: Week 12 ]
• Incidence of lab abnormalities [ Time Frame: Week 12 ]
• Incidence of vital sign abnormalities [ Time Frame: Week 12 ]
• Incidence of ECG abnormalities [ Time Frame: Week 12 ]

Original Secondary Outcome Measures (submitted: September 15, 2022)

• Change from baseline in physical activity as measured with remote digital sensors [ Time Frame: baseline, Week 12 ]
  evaluation of physical activity (Sedentary, light and moderate) and gait speed.
• change from baseline in Functional Assessment of Anorexia-Cachexia Therapy (FAACT-ACS and FAACT-5IASS) scores [ Time Frame: baseline, Week 12 ]
  FACT-G score sums 27 items; ACS score sums 12 items; both use a 5-point scale (0-4).Higher scores are associated with a higher health-related quality of life.
• Incidence of adverse events [ Time Frame: Week 12 ]
• Incidence of lab abnormalities [ Time Frame: Week 12 ]
• Incidence of vital sign abnormalities [ Time Frame: Week 12 ]
• Incidence of ECG abnormalities [ Time Frame: Week 12 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of the Efficacy and Safety of Ponsegromab in Patients With Cancer, Cachexia and Elevated GDF-15
• Official Title: 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)
• 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 Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
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

Primary Purpose: Treatment

Condition

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

Intervention

• Drug: ponsegromab
  Double-Blind ponsegromab Treatment followed by Open Label ponsegromab Treatment
• Drug: Placebo for ponsegromab
  Double-Blind placebo Treatment followed by Open Label ponsegromab Treatment

Study Arms

• Experimental: Double-Blind ponsegromab Treatment low dose followed by Open Label ponsegromab Treatment
  ponsegromab low dose subcutaneous injection every 4 weeks
  Intervention: Drug: ponsegromab
• Placebo Comparator: Double-Blind Placebo Treatment followed by Open-Label ponsegromab Treatment
  Match placebo subcutaneous injection every 4 weeks
  Intervention: Drug: Placebo for ponsegromab
• Experimental: Double-Blind ponsegromab Treatment medium dose followed by Open Label ponsegromab Treatment
  ponsegromab medium dose subcutaneous injection every 4 weeks
  Intervention: Drug: ponsegromab
• Experimental: Double-Blind ponsegromab Treatment high dose followed by Open Label ponsegromab Treatment
  ponsegromab high dose subcutaneous injection every 4 weeks
  Intervention: Drug: ponsegromab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 10, 2024): 187
• Original Estimated Enrollment (submitted: September 15, 2022): 168
• Estimated Study Completion Date: April 30, 2025
• Actual Primary Completion Date: March 13, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Bulgaria, Canada, China, Czechia, Hungary, Japan, Poland, Slovakia, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT05546476
• Other Study ID Numbers: C3651003; 2022-003016-87 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: April 2024