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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

30 May 2023 → 24 Apr 2025

Decision date (initial)

2024-04-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pfizer Inc

External identifiers

EU CT number

2023-510446-24-00

EudraCT number

2022-003016-87

ClinicalTrials.gov

NCT05546476

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Efficacy, Pharmacogenomic, Pharmacokinetic, Therapy

To evaluate the effect of ponsegromab compared with placebo on body weight in participants with cancer, cachexia, and elevated concentrations of GDF-15.

Secondary objectives 4

1. 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.
2. 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.
3. 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.
4. 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.

Conditions and MedDRA coding

Cancer cachexia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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.
2. Documented histologic or cytologic active diagnosis of NSCLC, PANC, or CRC and are currently receiving, or have completed, standard of care 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 <20 kg/m2 with involuntary weight loss of >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.
6. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

Exclusion criteria 13

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.
7. Current use of any prohibited concomitant medication(s) within 4 weeks prior to first dose of study intervention. Refer to Section 6.9.
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 through the duration of the study (including both Part A and B). Refer to Section 6.9.
9. Enrollment and previously dosed in a prior study with ponsegromab.
10. History of severe liver disease or cirrhosis, unrelated to metastatic cancer. Potential study participants with the following liver function test abnormalities will 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.
12. Current adherence to a calorie-restricted diet with the intention of weight loss.
13. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline body weight at Week 12.

Secondary endpoints 4

1. Change from baseline in each of the 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.
2. Change from baseline in FAACT sub-scale scores at Week 12: FAACT-ACS; FAACT-5IASS.
3. Change from baseline score for the questions from the CRCSD at Week 12 related to: Anorexia/appetite; Nausea and vomiting; Fatigue.
4. Incidence of adverse events, safety laboratory tests, vital signs and ECG abnormalities

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

John Groarke

Public contact point

Organisation

Pfizer Inc.

Contact name

John Groarke

Third parties 7

Locations

4 EU/EEA countries · 23 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications