NCT02718300

A Study of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis

Terminated Phase 2 Results posted Last updated 1 May 2024

What this trial tests

Phase 2 trial testing Parsaclisib in MPN (Myeloproliferative Neoplasms) in 74 participants. Terminated before completion.

Timeline

8 February 2017

Primary endpoint
28 January 2021

29 April 2022

Quick facts

Lead sponsor	Incyte Corporation
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	74
Start date	8 February 2017
Primary completion	28 January 2021
Estimated completion	29 April 2022
Sites	39 locations across United States

Drugs / interventions tested

• Parsaclisib — full drug profile →
• Parsaclisib — full drug profile →
• Ruxolitinib (RUXOLITINIB) — full drug profile →
• Parsaclisib — full drug profile →
• Parsaclisib — full drug profile →

Conditions studied

• MPN (Myeloproliferative Neoplasms) — all drugs for MPN (Myeloproliferative Neoplasms) →

Sponsor

Incyte Corporation — full company profile →

Who can join

18 and older, any sex, with MPN (Myeloproliferative Neoplasms). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Dose-limiting Toxicities (DLTs) Primary · up to Day 28

DLTs were defined as the occurrence of any protocol-defined toxicities occurring up to and including Day 28, except those with a clear alternative explanation (e.g., disease progression, other medications) or transient (≤ 72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. All DLTs were assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 criteria.

Group	Value	95% CI
TG5I/M	0
TG5D	0
TG10 + TG20: Daily/Weekly Dosing	0

Change From Baseline in Spleen Volume Through Week 12 of the Initial Study Period as Measured by Magnetic Resonance Imaging (MRI) (or Computed Tomography [CT] Scan in Applicable Participants) Primary · Baseline; Week 12

Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Baseline

Group	Value	95% CI
TG5I/M	1779.0	± 1006.75
TG5D	2032.3	± 773.45
TG10 + TG20: Daily/Weekly Dosing	2469.0	± 1208.90

Change from Baseline at Week 12

Group	Value	95% CI
TG5I/M	383.3	± 2342.09
TG5D	-276.9	± 226.11
TG10 + TG20: Daily/Weekly Dosing	-54.3	± 312.69

Percent Change From Baseline in Spleen Volume Through Week 12 as Measured by MRI (or CT Scan in Applicable Participants) Primary · Baseline; Week 12

Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] / Baseline value) x 100.

Group	Value	95% CI
TG5I/M	9.2	± 104.37
TG5D	-15.2	± 10.89
TG10 + TG20: Daily/Weekly Dosing	-3.1	± 12.21

Change From Baseline in Spleen Volume Through Week 24 of the Initial Study Period as Measured by MRI (or CT Scan in Applicable Participants) Secondary · Baseline; Week 24

Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Baseline

Group	Value	95% CI
TG5I/M	1779.0	± 1006.75
TG5D	2032.3	± 773.45
TG10 + TG20: Daily/Weekly Dosing	2469.0	± 1208.90

Change from Baseline at Week 24

Group	Value	95% CI
TG5I/M	-292.6	± 514.91
TG5D	-335.9	± 204.19
TG10 + TG20: Daily/Weekly Dosing	-37.5	± 432.02

Percent Change From Baseline in Spleen Volume Through Week 24 as Measured by MRI (or CT Scan in Applicable Participants ) Secondary · Baseline; Week 24

Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] / Baseline value) x 100.

Group	Value	95% CI
TG5I/M	-21.9	± 24.10
TG5D	-19.0	± 11.23
TG10 + TG20: Daily/Weekly Dosing	-4.9	± 18.81

Change From Baseline in the Total Symptom Score (TSS) Through Week 12 as Measured by Myelofibrosis Symptom Assessment Form (MFSAF) Version 3.0 (v3.0) Symptom Diary Secondary · Baseline; Week 12

The MFSAF v3.0 is comprised of 19 individual symptom scores, each collected daily using an 11-point scale. The daily TSS is composed of 6 of these individual symptom scores (nights sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone/muscle pain) collected on the same day. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 6 symptom scores; scores ranged from 0 to 60, with higher scores corresponding to more severe symptoms. The Baseline TSS was defined as the average of daily total score

Baseline

Group	Value	95% CI
TG5I/M	17.6	± 10.59
TG5D	16.3	± 12.82
TG10 + TG20: Daily/Weekly Dosing	15.2	± 12.94

Change from Baseline at Week 12

Group	Value	95% CI
TG5I/M	-6.0	± 6.63
TG5D	-5.0	± 11.15
TG10 + TG20: Daily/Weekly Dosing	-2.1	± 4.87

Percent Change From Baseline in the TSS Through Week 12 as Measured by MFSAF v3.0 Symptom Diary Secondary · Baseline; Week 12

The MFSAF v3.0 is comprised of 19 individual symptom scores, each collected daily using an 11-point scale. The daily TSS is composed of 6 of these individual symptom scores (nights sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone/muscle pain) collected on the same day. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 6 symptom scores; scores ranged from 0 to 60, with higher scores corresponding to more severe symptoms. The Baseline TSS was defined as the average of daily total score

Group	Value	95% CI
TG5I/M	-37.0	± 30.93
TG5D	-17.7	± 57.81
TG10 + TG20: Daily/Weekly Dosing	10.1	± 118.94

Change From Baseline in the TSS Through Week 24 as Measured by MFSAF v3.0 Symptom Diary Secondary · Baseline; Week 24

The MFSAF v3.0 is comprised of 19 individual symptom scores, each collected daily using an 11-point scale. The daily TSS is composed of 6 of these individual symptom scores (nights sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone/muscle pain) collected on the same day. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 6 symptom scores; scores ranged from 0 to 60, with higher scores corresponding to more severe symptoms. The Baseline TSS was defined as the average of daily total score

Baseline

Group	Value	95% CI
TG5I/M	17.6	± 10.59
TG5D	16.3	± 12.82
TG10 + TG20: Daily/Weekly Dosing	15.2	± 12.94

Change from Baseline at Week 24

Group	Value	95% CI
TG5I/M	-5.6	± 8.97
TG5D	-3.9	± 13.63
TG10 + TG20: Daily/Weekly Dosing	-2.0	± 7.15

Percent Change From Baseline in the TSS Through Week 24 as Measured by MFSAF v3.0 Symptom Diary Secondary · Baseline; Week 24

The MFSAF v3.0 is comprised of 19 individual symptom scores, each collected daily using an 11-point scale. The daily TSS is composed of 6 of these individual symptom scores (nights sweats, itchiness, abdominal discomfort, pain under left ribs, early satiety, bone/muscle pain) collected on the same day. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 6 symptom scores; scores ranged from 0 to 60, with higher scores corresponding to more severe symptoms. The Baseline TSS was defined as the average of daily total score

Group	Value	95% CI
TG5I/M	-29.2	± 41.08
TG5D	-16.7	± 76.27
TG10 + TG20: Daily/Weekly Dosing	11.1	± 80.23

Change From Baseline in the TSS Through Week 12 as Measured by Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Secondary · Baseline; Week 12

The MPN-SAF weekly total score is defined as the sum of 10 individual symptom scores (fatigue, nights sweats, itchiness, bone pain, fever, unintentional weight loss last 6 months, early satiety, abdominal discomfort, inactivity, problems with concentration) collected at the same visit using an 11-point scale. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 10 symptom scores; scores ranged from 0 to 100, with higher scores corresponding to more severe symptoms. Change from Baseline was calculated as the post-Baselin

Baseline

Group	Value	95% CI
TG5I/M	30.0	± 17.88
TG5D	27.7	± 18.18
TG10 + TG20: Daily/Weekly Dosing	29.2	± 19.56

Change from Baseline at Week 12

Group	Value	95% CI
TG5I/M	-10.6	± 12.63
TG5D	-12.6	± 15.52
TG10 + TG20: Daily/Weekly Dosing	-4.8	± 9.78

Percent Change From Baseline in the TSS Through Week 12 as Measured by MPN-SAF Secondary · Baseline; Week 12

The MPN-SAF weekly total score is defined as the sum of 10 individual symptom scores (fatigue, nights sweats, itchiness, bone pain, fever, unintentional weight loss last 6 months, early satiety, abdominal discomfort, inactivity, problems with concentration) collected at the same visit using an 11-point scale. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 10 symptom scores; scores ranged from 0 to 100, with higher scores corresponding to more severe symptoms. Percent change from Baseline was calculated as the (\[p

Group	Value	95% CI
TG5I/M	-28.7	± 42.48
TG5D	-38.1	± 44.76
TG10 + TG20: Daily/Weekly Dosing	-20.1	± 40.88

Change From Baseline in the TSS Through Week 24 as Measured by MPN-SAF Secondary · Baseline; Week 24

The MPN-SAF weekly total score is defined as the sum of 10 individual symptom scores (fatigue, nights sweats, itchiness, bone pain, fever, unintentional weight loss last 6 months, early satiety, abdominal discomfort, inactivity, problems with concentration) collected at the same visit using an 11-point scale. Participants scored each symptom using a scale from 0 (absent) to 10 (worst imaginable). The TSS was calculated as a sum of all 10 symptom scores; scores ranged from 0 to 100, with higher scores corresponding to more severe symptoms. Change from Baseline was calculated as the post-Baselin

Baseline

Group	Value	95% CI
TG5I/M	30.0	± 17.88
TG5D	27.7	± 18.18
TG10 + TG20: Daily/Weekly Dosing	29.2	± 19.56

Change from Baseline at Week 24

Group	Value	95% CI
TG5I/M	-15.6	± 9.95
TG5D	-12.6	± 16.46
TG10 + TG20: Daily/Weekly Dosing	-10.3	± 11.88

Adverse events — posted to ClinicalTrials.gov

Time frame: up to approximately 1529 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

TG10: Daily/Weekly Dosing

Serious: 2/14 (14%)

Deaths: 6/14

TG20: Daily/Weekly Dosing

Serious: 11/18 (61%)

Deaths: 11/18

TG5I/M

Serious: 7/21 (33%)

Deaths: 4/21

TG5D

Serious: 6/21 (29%)

Deaths: 5/21

Total: Initially Randomized Participants

Serious: 26/74 (35%)

Deaths: 26/74

TG5D Transition

Serious: 3/8 (38%)

Deaths: 3/8

Serious adverse events (43 terms)

Reaction	System	TG10: Daily/Weekly Dosing	TG20: Daily/Weekly Dosing	TG5I/M	TG5D	Total: Initially Randomize…	TG5D Transition
Pneumonia	Infections and infestations	—	—	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—
Angina pectoris	Cardiac disorders	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Bacteraemia	Infections and infestations	—	—	—	—	—	—
Blast crisis in myelogenous leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—
Blood bilirubin increased	Investigations	—	—	—	—	—	—
Breast cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—
Chest pain	General disorders	—	—	—	—	—	—
Cholecystitis infective	Infections and infestations	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—
Disseminated tuberculosis	Infections and infestations	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Haematoma	Vascular disorders	—	—	—	—	—	—
Haemorrhage intracranial	Nervous system disorders	—	—	—	—	—	—
Herpes zoster	Infections and infestations	—	—	—	—	—	—
Hypervolaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Influenza	Infections and infestations	—	—	—	—	—	—
Intra-abdominal haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—
Liver function test increased	Investigations	—	—	—	—	—	—

Other adverse events (183 terms — click to expand)

Reaction	System	TG10: Daily/Weekly Dosing	TG20: Daily/Weekly Dosing	TG5I/M	TG5D	Total: Initially Randomize…	TG5D Transition
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—	—	—
Hyperuricaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Blood creatinine increased	Investigations	—	—	—	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—	—	—
Muscular weakness	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Hyperkalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Night sweats	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—	—

Most-reported serious reactions: Pneumonia, Fall, Pyrexia, Urinary tract infection, Abdominal pain, Angina pectoris, Arthralgia, Bacteraemia.

Data from ClinicalTrials.gov NCT02718300 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the safety, tolerability, and efficacy of the combination of parsaclisib and ruxolitinib in subjects with myelofibrosis.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting PI3K in cancer: mechanisms and advances in clinical trials.
   Yang J, Nie J, Ma X, Wei Y, et al · · 2019 · cited 1142× · PMID 30782187 · DOI 10.1186/s12943-019-0954-x
2. PI3K inhibitors are finally coming of age.
   Vanhaesebroeck B, Perry MWD, Brown JR, André F, et al · · 2021 · cited 353× · PMID 34127844 · DOI 10.1038/s41573-021-00209-1
3. Management of myelofibrosis after ruxolitinib failure.
   Harrison CN, Schaap N, Mesa RA. · · 2020 · cited 70× · PMID 32198525 · DOI 10.1007/s00277-020-04002-9
4. Myelofibrosis in 2019: moving beyond JAK2 inhibition.
   Schieber M, Crispino JD, Stein B. · · 2019 · cited 54× · PMID 31511492 · DOI 10.1038/s41408-019-0236-2
5. Novel therapeutics in myeloproliferative neoplasms.
   Venugopal S, Mascarenhas J. · · 2020 · cited 32× · PMID 33267911 · DOI 10.1186/s13045-020-00995-y
6. Beyond Ruxolitinib: Fedratinib and Other Emergent Treatment Options for Myelofibrosis.
   Bewersdorf JP, Jaszczur SM, Afifi S, Zhao JC, et al · · 2019 · cited 28× · PMID 31920387 · DOI 10.2147/cmar.s212559
7. Challenges and Perspectives for Therapeutic Targeting of Myeloproliferative Neoplasms.
   Brkic S, Meyer SC. · · 2021 · cited 26× · PMID 33403355 · DOI 10.1097/hs9.0000000000000516
8. Targeted therapies for myeloproliferative neoplasms.
   Li B, Rampal RK, Xiao Z. · · 2019 · cited 17× · PMID 31346467 · DOI 10.1186/s40364-019-0166-y