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

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

Detailed Description
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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.

Official Title
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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)

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

Intervention / Treatment
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* Drug: ponsegromab
* Drug: Placebo for ponsegromab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Double-Blind ponsegromab Treatment low dose followed by Open Label ponsegromab Treatment<br>ponsegromab low dose subcutaneous injection every 4 weeks | Drug: ponsegromab<br>* Double-Blind ponsegromab Treatment followed by Open Label ponsegromab Treatment<br>|
| Placebo Comparator: Double-Blind Placebo Treatment followed by Open-Label ponsegromab Treatment<br>Match placebo subcutaneous injection every 4 weeks | Drug: Placebo for ponsegromab<br>* Double-Blind placebo Treatment followed by Open Label ponsegromab Treatment<br>|
| Experimental: Double-Blind ponsegromab Treatment medium dose followed by Open Label ponsegromab Treatment<br>ponsegromab medium dose subcutaneous injection every 4 weeks | Drug: ponsegromab<br>* Double-Blind ponsegromab Treatment followed by Open Label ponsegromab Treatment<br>|
| Experimental: Double-Blind ponsegromab Treatment high dose followed by Open Label ponsegromab Treatment<br>ponsegromab high dose subcutaneous injection every 4 weeks | Drug: ponsegromab<br>* Double-Blind ponsegromab Treatment followed by Open Label ponsegromab Treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in body weight for ponsegromab compared to placebo |  | baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in physical activity as measured with remote digital sensors | evaluation of physical activity (Sedentary, light and moderate) and gait speed. | baseline, Week 12 | 
| change from baseline in Functional Assessment of Anorexia-Cachexia Therapy (FAACT-ACS and FAACT-5IASS) scores | 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. | baseline, Week 12 | 
| Change from baseline in anorexia/appetite; Nausea and vomiting; and Fatigue as measured by the Cancer Related Cachexia Symptom Diary (CRCSD) | Self-reported questionnaire that measures severity of symptoms related to cancer cachexia: appetite, nausea, vomiting, and fatigue. | baseline, Week 12 | 
| Incidence of adverse events |  | Week 12 | 
| Incidence of lab abnormalities |  | Week 12 | 
| Incidence of vital sign abnormalities |  | Week 12 | 
| Incidence of ECG abnormalities |  | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, anorexia, cachexia, weight loss, loss of appetite, fatigue