Anemia Studies in Chronic Kidney Disease (CKD): Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat in Non-Dialysis Subjects Evaluating Hemoglobin (Hgb) and Quality of Life (ASCEND-NHQ)

NCT03409107 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 2052702017-002270-39
• Study Type: interventional
• Target: 614
• Locations: 14 countries
• Sites: 168

Brief Summary

The purpose of this multi-center study in non-dialysis participants with anemia associated with CKD is to evaluate safety, efficacy and quality of life of daprodustat compared to placebo.

Conditions

Anaemia

Keywords

Non-Dialysis; Anemia; Chronic kidney disease; Recombinant human erythropoietin naïve; Hemoglobin; Daprodustat

Outcome Measures

Primary Outcomes (1)

• Mean Change in Hemoglobin From Baseline and Over the Evaluation Period (Mean Over Week 24 and 28)

  Blood samples were collected at given time points from participants for hemoglobin measurements. Evaluation period hemoglobin value was defined as the mean of all available post-randomization hemoglobin values (on and off-treatment) during the evaluation period (Week 24 to Week 28 inclusive). For the primary analysis, the missing post-Baseline hemoglobin values were imputed using pre-specified multiple imputations. Change from Baseline was defined as the average of post-randomization values during the evaluation period minus Baseline value. Baseline value was the latest non-missing pre-dose assessment on or before the randomization date. Analysis was performed using the Analysis of Covariance (ANCOVA) model with terms for treatment, Baseline hemoglobin, and region.

  Baseline (Day 1) and Week 24 to Week 28

Secondary Outcomes (21)

• Percentage of Participants With Hemoglobin Increase of >=1.0 Grams Per Deciliter From Baseline to Evaluation Period

  Baseline (Day 1) and Week 24 to Week 28

• Change From Baseline in Short Form-36 (SF-36) Questionnaire Vitality Domain Score by Traditional Scoring at Week 28

  Baseline (Day 1) and Week 28

• Percentage of Participants With Hgb Response (Hgb in the 11-12 Grams/Deciliter Range) During Evaluation Period (Week 24 to Week 28 Inclusive)

  Week 24 to Week 28

• Percentage of Time With Hgb Within the Target Range (11-12 Grams Per Deciliter) During Evaluation Period (Week 24 to Week 28 Inclusive) (Hodges-Lehmann Estimate)

  Week 24 to Week 28

• Percentage of Time With Hgb Within the Target Range (11-12 Grams Per Deciliter) During Evaluation Period (Week 24 to Week 28 Inclusive) (Mann-Whitney Estimate)

  Week 24 to Week 28

Study Arms (2)

Daprodustat receivers

EXPERIMENTAL

Participants will receive oral daprodustat once daily

Drug: Daprodustat (GSK1278863); Drug: Iron therapy

Placebo receivers

PLACEBO COMPARATOR

Participants will receive oral placebo once daily

Drug: Placebo; Drug: Iron therapy

Interventions

Daprodustat (GSK1278863) DRUG

Daprodustat will be available as 9 millimeter (mm) or 7 mm film-coated tablets. Daprodustat will be administered once daily via oral route and can be taken without regard to food.

Daprodustat receivers

Placebo DRUG

Daprodustat matching placebo will be available as 9 mm or 7 mm film coated tablets. Placebo will be administered once daily via oral route and can be taken without regard to food.

Placebo receivers

Iron therapy DRUG

Iron therapy will be administered if ferritin is \<50 Nano gram per milliliter and/or TSAT is \<15 percent.

Daprodustat receivers; Placebo receivers

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>=18 years of age at the time of signing the informed consent.
• Have CKD, confirmed at screening: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3, 4, or 5 defined by Estimated glomerular filtration rate (eGFR) using the CKD Epidemiology Collaboration (CKD-EPI) formula.
• Participants with Stable HemoCue Hgb from 8.5 to 10.5 at screening visit (Week -4) and from 8.5 to 10.0 g/dL at randomization (Day 1).
• Participants may receive up to one intravenous (IV) iron dose within the 8 weeks prior to screening and NO IV iron use between screening visit and randomization (Day 1).
• If needed, participant may be on stable maintenance oral iron supplementation. There should be \<50% change in overall dose and no change in type of iron prescribed in the 4 weeks prior to Day 1 randomization visit.
• Male and female participants are eligible. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 4 weeks after the last dose of study treatment.
• Capable of giving signed informed consent.

You may not qualify if:

• Participants who are on dialysis or clinical evidence of impending need to initiate dialysis within 180 days after randomization (Day 1).
• Planned living-related or living-unrelated kidney transplant within 28 weeks after randomization (Day 1).
• Transferrin saturation (TSAT) \<15 percent (Screening only).
• Ferritin \<50 nanograms per milliliter (ng/mL) (Screening only).
• History of rhEPO or rhEPO analogue use within the 8 weeks prior to screening and rhEPO use between screening and randomization (Day 1).
• History of transfusion within the 8 weeks prior to screening and transfusion between screening and randomization (Day 1).
• History of bone marrow aplasia or pure red cell aplasia (PRCA).
• Participants with Megaloblastic anemia (untreated pernicious anemia and folate deficiency), thalassemia major, sickle cell disease or myelodysplastic syndrome.
• Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant gastrointestinal (GI) bleeding \<= 8 weeks prior to screening through to randomization (Day 1).
• History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product.
• Use of strong inhibitor of CYP2C8 (for example, gemfibrozil) or strong inducers of CYP2C8 (for example, rifampin/rifampicin).
• Ferric citrate use within 4 weeks prior to randomization (Day 1).
• Use of other investigational agent or device prior to screening through to randomization (Day 1).
• Any prior treatment with daprodustat for a treatment duration of \>30 days.
• MI or acute coronary syndrome within the 8 weeks prior to screening through to randomization. (Day 1).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (168)

GSK Investigational Site

Homewood, Alabama, 35209, United States

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Little Rock, Arkansas, 72204, United States

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Downey, California, 90242, United States

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Fresno, California, 93720, United States

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Lynwood, California, 90262, United States

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Northridge, California, 91324, United States

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Northridge, California, 91325, United States

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Riverside, California, 82503, United States

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Salinas, California, 93901, United States

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Santa Ana, California, 92704, United States

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Denver, Colorado, 80230, United States

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Hartford, Connecticut, 06112, United States

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Middlebury, Connecticut, 06762, United States

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Coral Springs, Florida, 33067, United States

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Hollywood, Florida, 33024, United States

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Kissimmee, Florida, 34741, United States

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Lauderdale Lakes, Florida, 33313, United States

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Pembroke Pines, Florida, 33028, United States

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Tampa, Florida, 33614, United States

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Adairsville, Georgia, 30103, United States

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Macon, Georgia, 31201, United States

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Macon, Georgia, 31217, United States

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Statesboro, Georgia, 30458, United States

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Indianapolis, Indiana, 46260, United States

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Overland Park, Kansas, 66210, United States

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Buckley, Michigan, 49620, United States

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Detroit, Michigan, 48202, United States

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Saint Clair Shores, Michigan, 48081, United States

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Brookhaven, Mississippi, 39601, United States

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St Louis, Missouri, 63136, United States

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Rochester, New Hampshire, 03867, United States

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Asheville, North Carolina, 28801, United States

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Charlotte, North Carolina, 28262, United States

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Durham, North Carolina, 27704, United States

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Midwest City, Oklahoma, 73130, United States

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Oklahoma City, Oklahoma, 73112, United States

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Beaver, Pennsylvania, 15009, United States

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Duncansville, Pennsylvania, 16635, United States

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Scottdale, Pennsylvania, 15683, United States

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Smithfield, Pennsylvania, 15478, United States

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West Reading, Pennsylvania, 19611, United States

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Orangeburg, South Carolina, 29118, United States

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Kingsport, Tennessee, 37660, United States

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Memphis, Tennessee, 38163, United States

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DeSoto, Texas, 75115, United States

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El Paso, Texas, 79935, United States

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McAllen, Texas, 78503, United States

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Waxahachie, Texas, 75165, United States

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Norfolk, Virginia, 23502, United States

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Ciudad Autonoma de Buenos Aires, Buenos Aires, C1128AAF, Argentina

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Ciudad Autonoma de Buenos Aires, Buenos Aires, C1425AGC, Argentina

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Mar del Plata, Buenos Aires, 7600, Argentina

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Mar del Plata, Buenos Aires, B7600FZN, Argentina

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San Nicolás de los Arroyos, Buenos Aires, B2900DMH, Argentina

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Córdoba, Córdoba Province, 5003, Argentina

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Rosario, Santa Fe Province, S2000DEJ, Argentina

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Santa Fe, 3000, Argentina

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Sydney, New South Wales, 2010, Australia

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Heidelberg, Victoria, 3084, Australia

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Parkville, Victoria, 3050, Australia

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Murdoch, Western Australia, 6150, Australia

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Fitzroy, 3065, Australia

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Vitória, Espírito Santo, 29055450, Brazil

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Feira de Santana, Estado de Bahia, 44001-584, Brazil

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Salvador, Estado de Bahia, 40415-065, Brazil

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Ribeirão Preto, São Paulo, 14025170, Brazil

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Santo André - SP, São Paulo, 09080-110, Brazil

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São Bernardo do Campo, São Paulo, 09715090, Brazil

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São José do Rio Preto, São Paulo, 15015200, Brazil

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São José do Rio Preto, São Paulo, 15090-000, Brazil

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São Paulo, 04038002, Brazil

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Victoria, British Columbia, V8V 4A1, Canada

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Brampton, Ontario, L6T 0G1, Canada

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Greater Sudbury, Ontario, P3A-1W8, Canada

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Guelph, Ontario, N1H 1B1, Canada

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Kitchener, Ontario, N2H 5Z8, Canada

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Ottawa, Ontario, K1H 1A2, Canada

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Sarnia, Ontario, N7T 4X3, Canada

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Toronto, Ontario, M5B 1W8, Canada

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Toronto, Ontario, M9N 1N8, Canada

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Toronto, Ontario, M9V 4B4, Canada

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Montreal, Quebec, H1M 1B1, Canada

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Québec, Quebec, G2J 0C4, Canada

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Québec, Quebec, G3K 2P8, Canada

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Saint-Charles-Borromée, Quebec, J6E 2B4, Canada

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Grenoble, 38043, France

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Le Mans, 72037, France

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Marseille, 13385, France

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Melun, 77000, France

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Mulhouse, 68070, France

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Nantes, 44093, France

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Nice, 06001, France

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Saint-Priest-en-Jarez, 42270, France

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Catanzaro, Calabria, 88100, Italy

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Napoli, Campania, 80131, Italy

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Bologna, Emilia-Romagna, 40138, Italy

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Modena, Emilia-Romagna, 41124, Italy

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Genoa, Liguria, 16132, Italy

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Pavia, Lombardy, 27100, Italy

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Mestre, Veneto, 30174, Italy

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León, Guanajuato, 37530, Mexico

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Guadalajara, Jalisco, 44150, Mexico

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Monterrey, Nuevo León, 64060, Mexico

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Boca del Rio, Veracruz, 24290, Mexico

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Córdoba, Veracruz, 94550, Mexico

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Mérida, Yucatán, 97070, Mexico

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Guadalajara, 44600, Mexico

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Mérida, 97000, Mexico

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Veracruz, 91900, Mexico

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Bialystok, 15-276, Poland

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Ciechanów, 06-400, Poland

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Krakow, 30510, Poland

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Krakow, 31-513, Poland

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Krakow, 31-559, Poland

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Lodz, 92-213, Poland

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Lublin, 20-064, Poland

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Oława, 55-200, Poland

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Pleszew, 63-300, Poland

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Sosnowiec, 41-200, Poland

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Szczecin, 70-111, Poland

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Świdnik, 21-040, Poland

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Tczew, 83-110, Poland

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Warsaw, 01-868, Poland

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Warsaw, 02-801, Poland

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Warsaw, 04-749, Poland

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Brasov, 500283, Romania

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Bucharest, 022328, Romania

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Bucharest, 042122, Romania

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Cluj-Napoca, 400139, Romania

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Craiova, 200642, Romania

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Deva, 330084, Romania

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Oradea, 410469, Romania

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Târgu Mureş, 540096, Romania

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Timișoara, 300723, Romania

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Izhevsk, 426061, Russia

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Kaliningrad, 236016, Russia

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Kemerovo, 650066, Russia

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Krasnoyarsk, 660022, Russia

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Moscow, 121359, Russia

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Nizhny Novgorod, 603126, Russia

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Pyatigorsk, 357500, Russia

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Pyatigorsk, 357538, Russia

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Rostov-on-Don, 344022, Russia

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Ryazan, 390037, Russia

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Saint Petersburg, 194355, Russia

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Saint Petersburg, 197022, Russia

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Stavropol, 355017, Russia

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Yaroslavl, 150000, Russia

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Yaroslavl, 150030, Russia

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Yaroslavl, 150062, Russia

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Busan, 49201, South Korea

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Busan, 49241, South Korea

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Daegu, 42415, South Korea

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Daegu, 42601, South Korea

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Gyeonggi-do, 463-712, South Korea

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Seongnam-si, Gyeonggi-do, 13620, South Korea

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Seoul, 03312, South Korea

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Seoul, 08308, South Korea

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Badalona, 08916, Spain

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Madrid, 28040, Spain

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Santiago de Compostela, 15890, Spain

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Canterbury, Kent, CT1 3NG, United Kingdom

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Derby, DE22 3NE, United Kingdom

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London, SE5 9RS, United Kingdom

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Peterborough, PE3 9GZ, United Kingdom

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Plymouth, PL6 8DH, United Kingdom

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Shrewsbury, SY3 8XQ, United Kingdom

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Swansea, SA6 6NL, United Kingdom

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Related Publications (2)

• Johansen KL, Cobitz AR, Singh AK, Macdougall IC, Lopes RD, Obrador GT, Kovesdy CP, Israni R, Jha V, Okoro T, Sprys M, Jolly S, Lindsay AC, Bhatt P, Camejo RR, Keeley T, Cizman B, Wheeler DC. The ASCEND-NHQ randomized trial found positive effects of daprodustat on hemoglobin and quality of life in patients with non-dialysis chronic kidney disease. Kidney Int. 2023 Jun;103(6):1180-1192. doi: 10.1016/j.kint.2023.02.019. Epub 2023 Mar 2.

  PMID: 36868377 BACKGROUND

• Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.

  PMID: 36005278 DERIVED

MeSH Terms

Conditions

Anemia; Renal Insufficiency, Chronic

Interventions

GSK1278863

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This will be a double-blind study. The participant, investigator, site staff, and study team will be blinded to the assigned study treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to receive Daprodustat or placebo in a randomized manner.

Study Record Dates

• First Submitted: January 8, 2018
• First Posted: January 24, 2018
• Study Start: March 5, 2018
• Primary Completion: October 7, 2020
• Study Completion: October 7, 2020
• Last Updated: April 2, 2024
• Results First Posted: November 3, 2021

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

AR (8); CA (14); FR (8); ES (3); GB (7); BR (9); AU (5); RU (16); PL (16); IT (7); RO (9); ME (9); US (49); KR (8)