Trial Outcomes & Findings for Study of the Efficacy and Safety of Ponsegromab in Patients With Cancer, Cachexia and Elevated GDF-15 (NCT NCT05546476)

Last Updated: 2025-05-31

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

187 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2025-05-31

Participant Flow

A total of 187 participants were enrolled in this study. This study had 2 parts: Part A and Part B. On completion of Part A, participants had the opportunity to enter open-label extension period Part B (optional). Results are reported on the primary completion date of the study. At this milestone Part A analysis (primary and secondary outcome measures) was final.

Participant milestones

Participant milestones
Measure	Part A: Placebo/ Part B: Ponsegromab 400 mg Part A: Participants were randomized to receive placebo matching to Ponsegromab subcutaneously (SC) once in every 4 weeks (Q4W) up to 12 weeks (total of 3 doses). Part B: On completion of Part A, participants had the opportunity to receive open label Ponsegromab 400 mg Q4W SC for up to 1 year.	Part A: Ponsegromab 100 mg/ Part B: Ponsegromab 400 mg Part A: Participants were randomized to receive Ponsegromab 100 milligrams (mg) SC Q4W up to 12 weeks (total of 3 doses). Part B: On completion of Part A, participants had the opportunity to receive open label Ponsegromab 400 mg Q4W SC for up to 1 year.	Part A: Ponsegromab 200 mg/ Part B: Ponsegromab 400 mg Part A: Participants were randomized to receive Ponsegromab 200 mg SC Q4W up to 12 weeks (total of 3 doses). Part B: On completion of Part A, participants had the opportunity to receive open label Ponsegromab 400 mg Q4W SC for up to 1 year.	Part A: Ponsegromab 400 mg/ Part B: Ponsegromab 400 mg Part A: Participants were randomized to receive Ponsegromab 400 mg SC Q4W up to 12 weeks (total of 3 doses). Part B: On completion of Part A, participants had the opportunity to receive open label Ponsegromab 400 mg Q4W SC for up to 1 year.
Period 1: Part A STARTED	45	46	46	50
Period 1: Part A COMPLETED	32	32	39	34
Period 1: Part A NOT COMPLETED	13	14	7	16
Period 2: Part B STARTED	26	27	35	29
Period 2: Part B COMPLETED	0	0	0	0
Period 2: Part B NOT COMPLETED	26	27	35	29

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: Placebo/ Part B: Ponsegromab 400 mg Part A: Participants were randomized to receive placebo matching to Ponsegromab subcutaneously (SC) once in every 4 weeks (Q4W) up to 12 weeks (total of 3 doses). Part B: On completion of Part A, participants had the opportunity to receive open label Ponsegromab 400 mg Q4W SC for up to 1 year.	Part A: Ponsegromab 100 mg/ Part B: Ponsegromab 400 mg Part A: Participants were randomized to receive Ponsegromab 100 milligrams (mg) SC Q4W up to 12 weeks (total of 3 doses). Part B: On completion of Part A, participants had the opportunity to receive open label Ponsegromab 400 mg Q4W SC for up to 1 year.	Part A: Ponsegromab 200 mg/ Part B: Ponsegromab 400 mg Part A: Participants were randomized to receive Ponsegromab 200 mg SC Q4W up to 12 weeks (total of 3 doses). Part B: On completion of Part A, participants had the opportunity to receive open label Ponsegromab 400 mg Q4W SC for up to 1 year.	Part A: Ponsegromab 400 mg/ Part B: Ponsegromab 400 mg Part A: Participants were randomized to receive Ponsegromab 400 mg SC Q4W up to 12 weeks (total of 3 doses). Part B: On completion of Part A, participants had the opportunity to receive open label Ponsegromab 400 mg Q4W SC for up to 1 year.
Period 1: Part A Adverse Event	2	0	0	1
Period 1: Part A Death	4	4	5	6
Period 1: Part A Lack of Efficacy	0	0	0	1
Period 1: Part A Lost to Follow-up	0	0	0	1
Period 1: Part A Physician Decision	1	0	0	0
Period 1: Part A Progressive disease	3	5	0	1
Period 1: Part A Withdrawal by Subject	1	1	1	2
Period 1: Part A Global deterioration of health status	2	2	1	4
Period 1: Part A Other: Unspecified	0	2	0	0
Period 2: Part B Ongoing	26	27	35	29

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: Placebo/ Part B: Ponsegromab 400 mg n=45 Participants Part A: Participants were randomized to receive placebo matching to Ponsegromab SC Q4W up to 12 weeks (total of 3 doses). Part B: On completion of Part A, participants had the opportunity to receive open label Ponsegromab 400 mg Q4W SC for up to 1 year.	Part A: Ponsegromab 100 mg/ Part B: Ponsegromab 400 mg n=46 Participants Part A: Participants were randomized to receive Ponsegromab 100 mg SC Q4W up to 12 weeks (total of 3 doses). Part B: On completion of Part A, participants had the opportunity to receive open label Ponsegromab 400 mg Q4W SC for up to 1 year.	Part A: Ponsegromab 200 mg/ Part B: Ponsegromab 400 mg n=46 Participants Part A: Participants were randomized to receive Ponsegromab 200 mg SC Q4W up to 12 weeks (total of 3 doses). Part B: On completion of Part A, participants had the opportunity to receive open label Ponsegromab 400 mg Q4W SC for up to 1 year.	Part A: Ponsegromab 400 mg/ Part B: Ponsegromab 400 mg n=50 Participants Part A: Participants were randomized to receive Ponsegromab 400 mg SC Q4W up to 12 weeks (total of 3 doses). Part B: On completion of Part A, participants had the opportunity to receive open label Ponsegromab 400 mg Q4W SC for up to 1 year.	Total n=187 Participants Total of all reporting groups
Age, Continuous	63.2 Years STANDARD_DEVIATION 11.26 • n=5 Participants	70.1 Years STANDARD_DEVIATION 9.38 • n=7 Participants	65.9 Years STANDARD_DEVIATION 9.61 • n=5 Participants	66.1 Years STANDARD_DEVIATION 9.93 • n=4 Participants	66.4 Years STANDARD_DEVIATION 10.28 • n=21 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	19 Participants n=7 Participants	15 Participants n=5 Participants	18 Participants n=4 Participants	69 Participants n=21 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	27 Participants n=7 Participants	31 Participants n=5 Participants	32 Participants n=4 Participants	118 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants	9 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	43 Participants n=5 Participants	42 Participants n=7 Participants	44 Participants n=5 Participants	43 Participants n=4 Participants	172 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	18 Participants n=5 Participants	19 Participants n=7 Participants	18 Participants n=5 Participants	15 Participants n=4 Participants	70 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	26 Participants n=5 Participants	27 Participants n=7 Participants	28 Participants n=5 Participants	35 Participants n=4 Participants	116 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: Censored analysis set included all evaluable participants. For participants who discontinued study intervention, or received a prohibited procedure or prohibited medication, all observations post-discontinuation, or post-procedure, were censored and treated as missing data. For participants who missed a dose, or received an incomplete dose, all observations post-missed/incomplete dose were censored and treated as missing data.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=45 Participants Part A: Participants were randomized to receive placebo matching to Ponsegromab SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 100 mg n=46 Participants Part A: Participants were randomized to receive Ponsegromab 100 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 200 mg n=46 Participants Part A: Participants were randomized to receive Ponsegromab 200 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 400 mg n=50 Participants Part A: Participants were randomized to receive Ponsegromab 400 mg SC Q4W up to 12 weeks (total of 3 doses).
Part A: Change From Baseline in Body Weight at Week 12	NA Kilogram Measure Type = Posterior Median = -0.60 Measure of Dispersion = 90% Credible Interval = -1.50 to 0.24	NA Kilogram Measure Type = Posterior Median = 0.75 Measure of Dispersion = 90% Credible Interval = 0.06 to 1.44	NA Kilogram Measure Type = Posterior Median = 1.48 Measure of Dispersion = 90% Credible Interval = 0.87 to 2.08	NA Kilogram Measure Type = Posterior Median = 2.39 Measure of Dispersion = 90% Credible Interval = 1.49 to 3.34

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Censored analysis set:all evaluable participants.For participants who discontinued study intervention/received prohibited procedure/ prohibited medication,all observations post-discontinuation/post-procedure,were censored and treated as missing data.For participants who missed dose/received incomplete dose,all observations post-missed/incomplete dose were censored and treated as missing data.''Overall Number of Participants Analyzed'' =participants evaluable for this outcome measure at 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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=12 Participants Part A: Participants were randomized to receive placebo matching to Ponsegromab SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 100 mg n=17 Participants Part A: Participants were randomized to receive Ponsegromab 100 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 200 mg n=16 Participants Part A: Participants were randomized to receive Ponsegromab 200 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 400 mg n=13 Participants Part A: Participants were randomized to receive Ponsegromab 400 mg SC Q4W up to 12 weeks (total of 3 doses).
Part A: Change From Baseline in Physical Activity at Week 12 Time for Sedentary Activity	-1.42 Minutes per day Interval -72.77 to 69.92	51.93 Minutes per day Interval -9.88 to 113.75	-39.33 Minutes per day Interval -101.94 to 23.29	-3.37 Minutes per day Interval -72.89 to 66.14
Part A: Change From Baseline in Physical Activity at Week 12 Time for Non-Sedentary Physical Activity	-37.73 Minutes per day Interval -66.14 to -9.32	0.03 Minutes per day Interval -24.88 to 24.95	-42.09 Minutes per day Interval -67.63 to -16.56	12.11 Minutes per day Interval -14.87 to 39.1
Part A: Change From Baseline in Physical Activity at Week 12 Time for Moderate to Vigorous Physical Activity	-4.45 Minutes per day Interval -13.91 to 5.02	4.07 Minutes per day Interval -4.18 to 12.32	0.05 Minutes per day Interval -8.29 to 8.39	3.67 Minutes per day Interval -5.37 to 12.71

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=12 Participants Part A: Participants were randomized to receive placebo matching to Ponsegromab SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 100 mg n=17 Participants Part A: Participants were randomized to receive Ponsegromab 100 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 200 mg n=16 Participants Part A: Participants were randomized to receive Ponsegromab 200 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 400 mg n=13 Participants Part A: Participants were randomized to receive Ponsegromab 400 mg SC Q4W up to 12 weeks (total of 3 doses).
Part A: Change From Baseline in Mean Activity Level During Maximum 6 Minutes at Week 12	70.81 Arbitrary units per day (au/day) Interval -785.82 to 927.45	-59.46 Arbitrary units per day (au/day) Interval -794.41 to 675.49	794.96 Arbitrary units per day (au/day) Interval 39.43 to 1550.48	256.43 Arbitrary units per day (au/day) Interval -561.29 to 1074.16

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Censored analysis set: all evaluable participants. For participants who discontinued study intervention/received prohibited procedure/ prohibited medication,all observations post-discontinuation/post-procedure,were censored and treated as missing data.For participants who missed dose/received incomplete dose,all observations post-missed/incomplete dose were censored and treated as missing data.''Overall Number of Participants Analyzed''=participants evaluable for this outcome measure at 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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=12 Participants Part A: Participants were randomized to receive placebo matching to Ponsegromab SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 100 mg n=17 Participants Part A: Participants were randomized to receive Ponsegromab 100 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 200 mg n=16 Participants Part A: Participants were randomized to receive Ponsegromab 200 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 400 mg n=13 Participants Part A: Participants were randomized to receive Ponsegromab 400 mg SC Q4W up to 12 weeks (total of 3 doses).
Part A: Change From Baseline in Total Vector Magnitude at Week 12	-1919.02 Total activity counts/100 per day Interval -3450.37 to -387.68	-331.76 Total activity counts/100 per day Interval -1679.81 to 1016.29	-2017.57 Total activity counts/100 per day Interval -3387.48 to -647.65	284.15 Total activity counts/100 per day Interval -1175.46 to 1743.77

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=15 Participants Part A: Participants were randomized to receive placebo matching to Ponsegromab SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 100 mg n=19 Participants Part A: Participants were randomized to receive Ponsegromab 100 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 200 mg n=18 Participants Part A: Participants were randomized to receive Ponsegromab 200 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 400 mg n=14 Participants Part A: Participants were randomized to receive Ponsegromab 400 mg SC Q4W up to 12 weeks (total of 3 doses).
Part A: Change From Baseline in Gait at Week 12 Gait Speed	-0.008 Meter per second (m/s) Interval -0.042 to 0.026	-0.009 Meter per second (m/s) Interval -0.04 to 0.023	-0.012 Meter per second (m/s) Interval -0.044 to 0.019	0.009 Meter per second (m/s) Interval -0.024 to 0.042
Part A: Change From Baseline in Gait at Week 12 95th percentile of gait speed	0.011 Meter per second (m/s) Interval -0.041 to 0.064	0.011 Meter per second (m/s) Interval -0.037 to 0.059	-0.015 Meter per second (m/s) Interval -0.063 to 0.033	0.021 Meter per second (m/s) Interval -0.03 to 0.072

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=30 Participants Part A: Participants were randomized to receive placebo matching to Ponsegromab SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 100 mg n=27 Participants Part A: Participants were randomized to receive Ponsegromab 100 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 200 mg n=33 Participants Part A: Participants were randomized to receive Ponsegromab 200 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 400 mg n=27 Participants Part A: Participants were randomized to receive Ponsegromab 400 mg SC Q4W up to 12 weeks (total of 3 doses).
Part A: Change From Baseline in Functional Assessment of Anorexia-Cachexia Therapy- Anorexia and Cachexia Subscale (FAACT-ACS) at Week 12	0.52 Units on a scale Interval -1.6 to 2.63	4.76 Units on a scale Interval 2.54 to 6.97	1.15 Units on a scale Interval -0.9 to 3.2	4.63 Units on a scale Interval 2.4 to 6.85

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=30 Participants Part A: Participants were randomized to receive placebo matching to Ponsegromab SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 100 mg n=27 Participants Part A: Participants were randomized to receive Ponsegromab 100 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 200 mg n=33 Participants Part A: Participants were randomized to receive Ponsegromab 200 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 400 mg n=27 Participants Part A: Participants were randomized to receive Ponsegromab 400 mg SC Q4W up to 12 weeks (total of 3 doses).
Part A: Change From Baseline in FAACT- 5-Item Anorexia Symptom Scale (5IASS) at Week 12	0.15 Units on a scale Interval -0.97 to 1.27	2.50 Units on a scale Interval 1.32 to 3.67	0.15 Units on a scale Interval -0.94 to 1.24	2.45 Units on a scale Interval 1.28 to 3.62

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=24 Participants Part A: Participants were randomized to receive placebo matching to Ponsegromab SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 100 mg n=30 Participants Part A: Participants were randomized to receive Ponsegromab 100 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 200 mg n=26 Participants Part A: Participants were randomized to receive Ponsegromab 200 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 400 mg n=27 Participants Part A: Participants were randomized to receive Ponsegromab 400 mg SC Q4W up to 12 weeks (total of 3 doses).
Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue Appetite	-0.23 Units on a scale Interval -0.83 to 0.37	0.20 Units on a scale Interval -0.36 to 0.76	0.23 Units on a scale Interval -0.37 to 0.82	0.69 Units on a scale Interval 0.11 to 1.27
Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue Nausea	-0.33 Units on a scale Interval -0.82 to 0.17	0.14 Units on a scale Interval -0.32 to 0.61	0.06 Units on a scale Interval -0.43 to 0.55	-0.50 Units on a scale Interval -0.98 to -0.02
Part A: Change From Baseline in Cancer-Related Cachexia Symptom Diary (CRCSD) Scores at Week 12: Appetite, Nausea and Physical Fatigue Physical Fatigue	-0.27 Units on a scale Interval -0.85 to 0.32	0.39 Units on a scale Interval -0.16 to 0.94	0.38 Units on a scale Interval -0.21 to 0.96	-0.06 Units on a scale Interval -0.63 to 0.51

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=24 Participants Part A: Participants were randomized to receive placebo matching to Ponsegromab SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 100 mg n=30 Participants Part A: Participants were randomized to receive Ponsegromab 100 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 200 mg n=26 Participants Part A: Participants were randomized to receive Ponsegromab 200 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 400 mg n=27 Participants Part A: Participants were randomized to receive Ponsegromab 400 mg SC Q4W up to 12 weeks (total of 3 doses).
Part A: Median Change From Baseline in CRCSD Scores at Week 12: Vomiting Frequency	0.00 Units on a scale Interval 0.0 to 0.0	0.00 Units on a scale Interval 0.0 to 0.0	0.00 Units on a scale Interval 0.0 to 0.0	0.00 Units on a scale Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=45 Participants Part A: Participants were randomized to receive placebo matching to Ponsegromab SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 100 mg n=46 Participants Part A: Participants were randomized to receive Ponsegromab 100 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 200 mg n=46 Participants Part A: Participants were randomized to receive Ponsegromab 200 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 400 mg n=50 Participants Part A: Participants were randomized to receive Ponsegromab 400 mg SC Q4W up to 12 weeks (total of 3 doses).
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAE)	36 Participants	32 Participants	31 Participants	37 Participants

SECONDARY outcome

Timeframe: Day 1 up to Week 12

Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received. Here, ''Overall Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=37 Participants Part A: Participants were randomized to receive placebo matching to Ponsegromab SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 100 mg n=35 Participants Part A: Participants were randomized to receive Ponsegromab 100 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 200 mg n=40 Participants Part A: Participants were randomized to receive Ponsegromab 200 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 400 mg n=41 Participants Part A: Participants were randomized to receive Ponsegromab 400 mg SC Q4W up to 12 weeks (total of 3 doses).
Part A: Number of Participants With Incidence of Laboratory Test Abnormalities	26 Participants	24 Participants	29 Participants	28 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=40 Participants Part A: Participants were randomized to receive placebo matching to Ponsegromab SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 100 mg n=40 Participants Part A: Participants were randomized to receive Ponsegromab 100 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 200 mg n=44 Participants Part A: Participants were randomized to receive Ponsegromab 200 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 400 mg n=44 Participants Part A: Participants were randomized to receive Ponsegromab 400 mg SC Q4W up to 12 weeks (total of 3 doses).
Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria Supine SBP Value < 90mmHg	0 Participants	3 Participants	0 Participants	0 Participants
Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria Supine SBP Increase Change >= 30mmHg	4 Participants	5 Participants	8 Participants	2 Participants
Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria Supine SBP Decrease Change >= 30mmHg	2 Participants	6 Participants	5 Participants	4 Participants
Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria Supine DBP Value < 50mmHg	0 Participants	1 Participants	0 Participants	0 Participants
Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria Supine SBP Increase Change >= 20mmHg	4 Participants	4 Participants	3 Participants	4 Participants
Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria Supine DBP Decrease Change >= 20mmHg	3 Participants	4 Participants	4 Participants	3 Participants
Part A: Number of Participants With Post-Baseline Vital Signs Meeting the Predefined Criteria Supine Pulse Rate Value > 120mmHg	0 Participants	1 Participants	3 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 1 up to Week 12

Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

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.

Outcome measures

Outcome measures
Measure	Part A: Placebo n=45 Participants Part A: Participants were randomized to receive placebo matching to Ponsegromab SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 100 mg n=46 Participants Part A: Participants were randomized to receive Ponsegromab 100 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 200 mg n=46 Participants Part A: Participants were randomized to receive Ponsegromab 200 mg SC Q4W up to 12 weeks (total of 3 doses).	Part A: Ponsegromab 400 mg n=50 Participants Part A: Participants were randomized to receive Ponsegromab 400 mg SC Q4W up to 12 weeks (total of 3 doses).
Part A: Number of Participants With Clinically Significant Echocardiogram (ECG) Abnormalities	0 Participants	0 Participants	0 Participants	0 Participants

Adverse Events

Part A: Placebo

Serious events: 11 serious events

Other events: 25 other events

Deaths: 5 deaths

Part A: Ponsegromab 100 mg

Serious events: 15 serious events

Other events: 19 other events

Deaths: 6 deaths

Part A: Ponsegromab 200 mg

Serious events: 10 serious events

Other events: 19 other events

Deaths: 6 deaths

Part A: Ponsegromab 400 mg

Serious events: 20 serious events

Other events: 24 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER