E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
excessive urinary oxalate excretion |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Determine the efficacy of ALLN-177 in reducing UOx excretion in subjects with enteric HOx
Evaluate the safety of ALLN-177 in subjects with enteric HOx |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated the Institutional Review Board (IRB)/Ethics Committee (EC)-approved informed consent form (ICF) before undergoing any Screening procedure 2. Is ≥ 18 years of age at Screening 3. Has a history of HOx (confirmed by documented UOx excretion ≥ 50 mg/24 hr in the most recent 24-hour urine collection obtained within 6 months prior to Screening) that is secondary to a known underlying enteric disorder associated with malabsorption (e.g., bariatric surgery, Crohn’s disease, short bowel syndrome, or other malabsorption syndrome) - Note: Subjects with known or suspected HOx (e.g., history of kidney stones or oxalate nephropathy) without a 24-hour urine collection to determine UOx excretion within ≤ 6 months of Screening may perform a pre-screening 24-hour urine collection after providing appropriate consent. This 24-hour urine collection can also be used to satisfy Inclusion Criterion No. 4, if obtained within 6 weeks prior to Screening 4. Has adequate (i.e., appropriate ratio of creatinine [mg]/body weight [kg] for gender) 24-hour urine collection at Screening, with resulting UOx excretion ≥ 50 mg/24 hr 5. Has provided 2 adequate 24-hour urine collections at Baseline, with average urinary oxalate ≥ 50 mg/24 hr (and neither is < 40 mg/24 hr). 6. For subjects taking concomitant medication for management of kidney stone risk factors (e.g., pyridoxine, thiazides, citrate supplements, allopurinol): has been on a stable dose regimen for >8 weeks prior to and during Screening, with no changes in dosing (dose level or dosing frequency) anticipated during the remainder of the study. 7. For female subjects: Is either medically incapable of pregnancy (e.g., has undergone hysterectomy or tubal ligation or has experienced prolonged [≥ 1year prior to Screening] amenorrhea) or, if a woman of childbearing potential, has a negative Screening serum pregnancy test, is not pregnant or nursing at Screening, and agrees to use an effective (approved by the Investigator) method of birth control for the duration of the study |
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E.4 | Principal exclusion criteria |
1. Has > 30% variability in the ratio of creatinine (mg)/body weight (kg) among the three 24-hour urine samples collected prior to randomization (1 at Screening, 2 at Baseline) 2. Is in acute renal failure or has an estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m2 at Screening 3. Has HOx with a known cause other than underlying enteric disorder associated with malabsorption (e.g., primary HOx) 4. Is unable or unwilling to discontinue Vitamin C supplementation at Screening and for the duration of the study 5. Any clinically significant findings during Screening, any ongoing clinically significant illness requiring changes in management within 4 weeks prior to or during Screening (e.g., flare of inflammatory bowel disease), or any planned surgical/invasive procedure during the study 6. Malignancy or treatment for malignancy within 12 months prior to screening with the exception of localized basal cell or squamous cell skin cancer or any cancer in situ ‒ Note: Subjects whose malignancy is in remission and who are on a stable dose of chronic suppressive or maintenance therapy are not excluded 7. Has an active autoimmune disorder or other condition requiring therapy with high doses of systemic steroids (i.e., >10 mg/day prednisone or equivalent) or intensification of other immunosuppressant therapy within 4 weeks prior to or during Screening ‒ Note: Stable subjects on low chronic or maintenance doses of steroids or other immunosuppressant drugs, including transplant recipients, are not excluded 8. Has received study drug (ALLN-177 or placebo) in any other ALLN-177 clinical study, or participation in another drug or device clinical trial within 30 days prior to or during Screening 9. Is not, per Investigator judgment, an ideal clinical trial candidate due to a personal issue (e.g., unwillingness/inability to comply with protocol) or medical condition (e.g., mental illness, laboratory abnormalities) that is likely to impede successful study completion |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoints • Percent change from baseline in 24-hour UOx excretion during Weeks 1-4
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints • Proportion of subjects with a ≥ 20% reduction from Baseline in 24-hour UOx excretion during Weeks 1-4 (alternate primary efficacy endpoint for ex-US submission) • Ordered categorical analysis of the percentage change from Baseline in 24-hour UOx excretion during Weeks 1-4 • Analysis of efficacy parameters by bariatric surgery vs. other enteric condition subgroup
Exploratory Endpoints • Change from Baseline to Week 4 in urine supersaturation of calcium oxalate |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Germany |
Italy |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |