ALLN-177 Pilot Study in patients with Enteric or Primary Hyperoxaluria
Research type
Research Study
Full title
Pilot Study of ALLN-177 in Adult and Pediatric Subjects Aged 12 Years or Older with Enteric or Primary Hyperoxaluria and Hyperoxalemia
IRAS ID
247142
Contact name
John A Sayer
Contact email
Sponsor organisation
Allena Pharmaceuticals, Inc.
Eudract number
2017-003547-38
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
0 years, 9 months, 16 days
Research summary
This is a multi-site, open label, single-arm, pilot study of ALLN-177 in adult and pediatric subjects aged 12 and older with enteric or primary hyperoxaluria who also have hyperoxalemia.
The study sites will be: Approximately 5-10 sites in the United States, Germany, UK.
The study is comprised of:
Screening and Baseline Period (up to 4 weeks): Subjects will undergo screening assessments including laboratory tests. Eligible subjects will obtain Baseline plasma oxalate and two outpatient 24-hr urine collections. In subjects on dialysis or with eGFR ≤15 mL/ min/1.73m2, 24-hour urine collections will not be obtained. Subjects will receive study materials and training at the visit preceding the Treatment Period.
Treatment Period: During this 12-week period, subjects will self-administer 2 capsules of ALLN-177 (by mouth [PO]) with each meal/snack, 5 times per day, for a total of 10 capsules administered per day. At Weeks 4, 8 and 12, blood samples will be taken and two 24-hour urine collections will be obtained for study assessments.
Follow-up: Subjects will have a final visit 4 weeks after their last dose of study drug.
Oxalate is both an end-product of metabolism and is also absorbed from the diet (certain fruits, cereals, and vegetables have particularly high oxalate content). The primary route of oxalate elimination is via the kidneys. Hyperoxaluria is a serious metabolic disorder and one of the major risk factors for nephrolithiasis, nephrocalcinosis, and systemic oxalosis that may lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD). Hyperoxaluria is defined as a urinary oxalate concentration greater than 0.45 mmoL/1.73 m2/24h (or ~ 40 mg/24h) at ages beyond infancy. Hyperoxaluria is either primary (genetic) due to endogenous overproduction by the liver, or more commonly, secondary due to over-absorption of oxalate from the diet.
There is currently no approved pharmacologic therapy specifically directed at reducing the absorption of dietary oxalate from the GI tract or its overproduction by the liver. Current management consists of recommendations to reduce dietary oxalate intake and increase calcium intake, calcium and citrate supplementation, thiazide diuretics, and increased fluid intake. Patients with primary HOx are also often treated with pyridoxine (vitamin B6), which can be effective in a subset of patients. Other management options are non-specific and of limited utility.
This key aims of this study are to evaluate whether ALLN-177 can reduce plasma oxalate levels in subjects with enteric or primary hyperoxaluria who have hyperoxalemia, and whether ALLN-177 can reduce urine oxalate levels in hyperoxaluric patients with chronic kidney disease (but GFR >15 mL/min).REC name
North East - Newcastle & North Tyneside 2 Research Ethics Committee
REC reference
18/NE/0172
Date of REC Opinion
29 Jun 2018
REC opinion
Further Information Favourable Opinion