A Study to Evaluate the Efficacy and Safety of Veverimer for the Treatment of Metabolic Acidosis

Официальное название

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Veverimer in Adults With CKD and Metabolic Acidosis

Обзор

The purpose of this study is is to evaluate the efficacy and safety of veverimer in treating adults with moderate-to-severe chronic kidney disease (CKD) and metabolic acidosis.

Вмешательства

• Препарат Veverimer
  Group 1: 9 g veverimer BID
• Препарат Placebo
  Group 2: 9 g PBO BID

Первичные конечные точки

• Efficacy of Veverimer by measuring change in serum bicarbonate concentration (SBC) [Срок оценки: Visits: Screening to Day 168]
• Efficacy of Veverimer in improving physical performance as assessed by the Sit-to-Stand 5 times test (STS5). [Срок оценки: Visits: Screening to Day 168]

Вторичные конечные точки (4)

• Efficacy of Veverimer in achieving SBC and responder thresholds. [Срок оценки: Visits: Screening to Day 168]
• Performance outcomes (PerfO). [Срок оценки: Visits: Screening to Day 168]
• Frailty and muscle mass assessment. [Срок оценки: Visits: Screening to Day 168]
• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]. [Срок оценки: Visits: Screening to Day 168]

Критерии участия

Критерии включения

• Have provided written informed consent prior to participation in the study.
• Male or female participants 18 years of age or older.
• Diagnosed with CKD (eGFR < 60 mL/min/1.73m2) and not expected to require renal replacement therapy (dialysis or kidney transplant) throughout the duration of the study.
• Within 6 months prior to screening have at least two SBC between 12 and 20 mmol/L, inclusive. If only one historical SBC is available, a second SBC may be drawn on screening visit S1 and analyzed by the local laboratory.
• Within screening period have two central laboratory SBC (at least 24 hours apart and more than 4 hours after food) between 12 and 21 mmol/L, inclusive.
• Willing to keep food consumption similar to baseline throughout the entire study.
• If taking oral alkali therapy, dose has been stable for at least 28 days prior to the start of screening and is expected to remain stable throughout the study.
• Women who are of childbearing potential must have a negative pregnancy test and agree to abstinence or to use contraception.

Критерии исключения

• Any participant deemed by the Investigator to be an inappropriate candidate for PerfO testing (e.g., severe musculoskeletal pain, non-ambulatory status), inability to complete STS5 without support or with a screening STS5 time < 10 seconds.
• History or current diagnosis of:

• Clinically significant gastroparesis or a history of bariatric surgery.
• Bowel obstruction, swallowing disorders, severe gastrointestinal disorders, including inflammatory bowel disease, major gastrointestinal surgery including gastrectomy, or known active gastric/duodenal ulcers.
• Severe recurrent diarrhea or constipation, as assessed by the Investigator.
• Pernicious anemia, atrophic or autoimmune gastritis, achlorhydria or hypochlorhydria.
• Ineligible per REVIVE GastroScreen test.
• Use of GI polymer binders or sodium zirconium cyclosilicate within 14 days prior to the start of screening or have an expectation to initiate treatment during the study.
• Use of acid reducing drugs, including PPIs, H2RAs or P-CABs within 14 days prior to the start of screening or have an expectation to initiate treatment during the study. Very sporadic use (one time per week or less) may be acceptable, as assessed by the Investigator.
• Initiation of GLP-1 receptor agonists within 6 months prior to the start of screening, or expectation to initiate use during the study. Participants that have been on a GLP-1 receptor agonist for more than 6 months and have maintained a stable dose and steady body weight for at least one month prior to the start of screening may be considered for enrollment, upon Medical Monitor review. GLP-1 receptor agonists also should not be started during the study.
• Participants that are taking any of the following medications and have not been on a stable dose for at least 14 days prior to the start of screening or have an expectation to change dose during the study: diuretics, non-ophthalmic carbonic anhydrase inhibitors, diabetes drugs, RAAS inhibitors, calcium or magnesium supplements, non-polymer phosphate binders, and SGLT-2 inhibitors. These medications also should not be started during the study.
• Active, recurrent, or metastatic malignancy at the start of screening.
• History of malignancy, except under the following conditions:

• Carcinoma in situ (e.g., of the cervix, breast, or bladder) that has been completely excised and shows no evidence of residual disease.
• Non-melanoma skin cancers (e.g., basal cell carcinoma, squamous cell carcinoma) that have been completely excised and show no evidence of recurrence.
• Low grade prostate cancer, in the opinion of the Investigator (i.e., no metastasis, Gleason score < 6), with no significant worsening for > 6 months prior to the screening visit.
• Any other malignancy that was treated with curative intent and has been in complete remission for ≥ 5 years prior to the screening visit.
• Two or more hospitalizations within 12 months prior to the start of screening or a hospitalization within the last 3 months prior to the start of screening due to fluid overload, heart failure, acute kidney injury (AKI) or electrolyte disorders, including hyperkalemia. Participants that have not been hospitalized within the past 3 months and whose condition is stable may be considered for enrollment.
• Screening hemoglobin < 9 g/dL.
• Low bicarbonate value(s) at time of screening that are due to underlying primary respiratory alkalosis.
• Investigational medication administration within 28 days prior to start of screening.
• Participants that are taking an average of > 30 units of insulin daily, unless recent (within last 6 months) hemoglobin A1C is < 6.5%.
• History of alcoholism or drug/chemical abuse within 1 year prior to the start of screening, in the opinion of the Investigator.
• Current, regular use of inhaled/ingested cannabis/THC products.
• Inability to take the IP or otherwise comply with the protocol.
• Any medical condition, uncontrolled systemic disease or serious concurrent illness that would significantly decrease study compliance or jeopardize the safety of the participant or affect the validity of the trial results, in the opinion of the Investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 22 центра

• Study Site — Chula Vista
• Study Site — Los Angeles
• Study Site — Sacramento
• Study Site — San Diego
• Study Site — Aurora
• Study Site — Edgewater
• Study Site — Miami Springs
• Study Site — Orlando
• … и ещё 14 центров

Идентификаторы

NCT: NCT07355062 · REN-012

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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