{"ok":true,"data":{"subject":{"kind":"trial","nctId":"NCT05212337","title":"FITMI - First In Treating Male Infertility","sponsor":"Martin Blomberg Jensen","phases":["PHASE2"],"status":"ACTIVE_NOT_RECRUITING","indication":null,"disease":"hypogonadism"},"rows":[{"n":1,"question":"Is the biology right?","flags":[{"id":"somatic_driver","label":"Somatic driver evidence","value":"no","detail":"None of TNFSF11 has somatic-mutation evidence in hypogonadism","rule":"Open Targets has somatic-mutation evidence for the target in this cancer","source":{"label":"Open Targets: TNFSF11 in hypogonadism","url":"https://platform.opentargets.org/evidence/ENSG00000120659/MONDO_0002146","date":"2026-11-12T07:02:57.665Z"},"context":[]},{"id":"human_genetic","label":"Human genetic evidence","value":"no","detail":"No germline or somatic evidence for TNFSF11 in hypogonadism","rule":"Any germline or somatic human genetic evidence for the target in this cancer, counted apart from animal-model and literature evidence","source":{"label":"Open Targets: TNFSF11 in hypogonadism","url":"https://platform.opentargets.org/evidence/ENSG00000120659/MONDO_0002146","date":"2026-11-12T07:02:57.665Z"},"context":[]},{"id":"pediatric_target","label":"Pediatric target","value":"no","detail":"Not on the FDA list","rule":"Target is on FDA's Pediatric Molecular Target List (relevant targets); membership alone neither requires nor waives a study","source":{"label":"FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01))","url":"https://www.fda.gov/media/191157/download?attachment","date":"2026-11-11T07:05:03Z"},"context":[]},{"id":"haematologic","label":"Haematologic cancer","value":"no","detail":"Solid tumour","rule":"From the indication, or the registry conditions when no indication matches","source":{"label":"ClinicalTrials.gov NCT05212337","url":"https://clinicaltrials.gov/study/NCT05212337","date":"2026-11-12T07:02:57.665Z"},"context":[{"figure":"Likelihood of approval from phase 1: 7.5% haematologic vs 4.6% solid","dataset":"BIO / Informa / QLS 2021","years":"2011–2020","caveat":"Population-level, not a prediction."}]}],"facts":[{"label":"TNFSF11 (via Denosumab)","text":"Evidence types in hypogonadism: literature; literature listed separately from human genetics. Datasources: europepmc.","source":{"label":"Open Targets: TNFSF11 in hypogonadism","url":"https://platform.opentargets.org/evidence/ENSG00000120659/MONDO_0002146","date":"2026-11-12T07:02:57.665Z"}}],"pending":[{"what":"Normal-tissue expression in vital organs","source":"Human Protein Atlas (ticket 36)"},{"what":"Pan-essential in cell lines","source":"DepMap (ticket 36)"},{"what":"Approved drug on this target","source":"Drugs@FDA (ticket 30)"}]},{"n":2,"question":"Can the result be trusted?","flags":[{"id":"randomised","label":"Randomised","value":"yes","detail":"Randomised allocation","rule":"Registry allocation field","source":{"label":"ClinicalTrials.gov NCT05212337","url":"https://clinicaltrials.gov/study/NCT05212337","date":"2026-11-12T07:02:57.665Z"},"context":[]},{"id":"small_denominator","label":"Small denominator","value":"no","detail":"180 enrolled; each patient moves a rate by 100 ÷ 180 = 0.6 points","rule":"Enrolment under 30; the arithmetic is shown, not a benchmark","source":{"label":"ClinicalTrials.gov NCT05212337","url":"https://clinicaltrials.gov/study/NCT05212337","date":"2026-11-12T07:02:57.665Z"},"context":[]},{"id":"primary_os","label":"Primary endpoint is overall survival","value":"no","detail":"The difference in sperm concentration (million pr. mL) on day 80","rule":"A registered primary outcome measure names overall survival","source":{"label":"ClinicalTrials.gov NCT05212337","url":"https://clinicaltrials.gov/study/NCT05212337","date":"2026-11-12T07:02:57.665Z"},"context":[{"figure":"Non-OS primary endpoint: odds ratio 2.79 for a positive phase 3","dataset":"Otsuka 2021, 400 phase 3 oncology trials","years":"to 2020","caveat":"Shown with the next figure: a surrogate is easier to hit, and often a weak guide to survival."},{"figure":"52% of surrogate-to-OS correlations are low","dataset":"Prasad 2015","years":"published to 2014","caveat":"Shown with the figure above."}]},{"id":"results_overdue","label":"Results overdue","value":"yes","detail":"Primary completion 2024-10-22, 24 months ago; no results posted","rule":"Primary completion (actual) more than 12 months ago and no results posted to the registry","source":{"label":"ClinicalTrials.gov NCT05212337","url":"https://clinicaltrials.gov/study/NCT05212337","date":"2026-11-12T07:02:57.665Z"},"context":[{"figure":"40.9% of applicable trials report results within a year","dataset":"Results-reporting studies summarised in spec §11","years":"all therapy areas","caveat":"All areas, not oncology only."}]}],"facts":[],"pending":[{"what":"Treated and evaluable counts, assessor, confirmed response, follow-up and data cutoff","source":"Readout extraction (ticket 32)"},{"what":"Primary endpoint changed between registry versions","source":"Registry versions in the store (ticket 32)"}]},{"n":3,"question":"What must it beat?","flags":[],"facts":[],"pending":[{"what":"Control-arm result and approved therapies for the same segment, with label links","source":"Drugs@FDA, FDA labels and readouts (tickets 30, 32)"}]},{"n":4,"question":"Too crowded, or too late?","flags":[],"facts":[{"label":"Stopped on this target","text":"33 terminated, withdrawn or suspended trials of drugs against TNFSF11; 2 give no reason. Reasons are quoted as the registry gives them on the target page.","source":{"label":"TNFSF11: what already stopped","url":"/target/ENSG00000120659#stopped","date":"2026-11-12T07:02:57.691Z"}}],"pending":[{"what":"Programs on the target by phase and months behind the leader","source":"Programs and Drugs@FDA (ticket 33)"}]},{"n":5,"question":"Can it be approved, and stay approved?","flags":[{"id":"single_country","label":"Single-country","value":"yes","detail":"The only site is in Denmark","rule":"All listed sites are in one country; the share of US sites is shown","source":{"label":"ClinicalTrials.gov NCT05212337","url":"https://clinicaltrials.gov/study/NCT05212337?tab=locations","date":"2026-11-12T07:02:57.665Z"},"context":[]},{"id":"eu_pip","label":"EU paediatric investigation plan","value":"yes","detail":"EMA/PE/0000229606 (Deferoxamine (mesylate);histidine;tryptophan;aspartic acid;n-acetyl-histidine (monohydrate);glycine;arginine;potassium chloride;calcium chloride (dihydrate);sodium chloride;alanine;3,4-dimethoxy-N-methylbenzohydroxamic;magnesium chloride hexahydrate;L-tryptophan;oxogluric acid;n-hydroxy-3, Cardioplegia): PM: decision on the application for modification of an agreed PIP, 14 Apr 2025; EMA/PE/0000229486 (histidine;tryptophan;aspartic acid;n-acetyl-histidine (monohydrate);glycine;alpha-ketoglutaric acid;arginine;potassium chloride;calcium chloride (dihydrate);sodium chloride;alanine;3,4-dimethoxy-N-methylbenzohydroxamic acid (Custodiol-N);magnesium chloride hexahydrate, Heart transplantation): PM: decision on the application for modification of an agreed PIP, 14 Apr 2025; EMA/PE/0000225241 (calcium chloride dihydrate;magnesium chloride hexahydrate;sodium chloride;sodium lactate;xylitol;d-glucose;levocarnitine, Acute pain;Treatment of renal failure): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 3 Jan 2025; EMEA-003049-PIP01-21-M01 (L-carnitine;glucose;calcium chloride dihydrate;sodium lactate;sodium chloride;magnesium chloride hexahydrate, Treatment of renal failure with carnitine deficiency): PM: decision on the application for modification of an agreed PIP, 15 Mar 2024; +5 more","rule":"An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name","source":{"label":"EMA data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-paediatric_investigation_plans-output-json-report_en.json","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"eu_orphan","label":"EU orphan designation","value":"no","detail":"No EU orphan designation names Denosumab, Sodium chloride","rule":"An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status","source":{"label":"EMA data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-orphan_designations-json-report_en.json","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"eu_authorised","label":"Authorised in the EU","value":"yes","detail":"Bildyos: authorised since 17 Sept 2025; Jubereq: authorised since 26 May 2025; Yaxwer: authorised since 23 Jun 2025; Prolia: authorised since 26 May 2010; +28 more","rule":"An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file","source":{"label":"EMA data download (dated snapshot)","url":"https://www.ema.europa.eu/en/documents/report/medicines-output-medicines_json-report_en.json","date":"2026-11-11T09:12:26Z"},"context":[]},{"id":"fda_orphan","label":"FDA orphan designation","value":"not published","detail":"FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the link","rule":"Would be: an FDA orphan designation names the drug","source":{"label":"FDA orphan designations search","url":"https://www.accessdata.fda.gov/scripts/opdlisting/oopd/","date":""},"context":[]},{"id":"fda_ped_approval","label":"FDA pediatric oncology approval","value":"yes","detail":"Denosumab [Xgeva], 13 Jun 2013: Treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity","rule":"FDA's Pediatric Oncology Drug Approvals table names the drug","source":{"label":"FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03)","url":"https://www.fda.gov/about-fda/oncology-center-excellence/pediatric-oncology-drug-approvals","date":"2026-11-12T07:02:57.723Z"},"context":[]},{"id":"studies_under_18","label":"Registered studies open to children","value":"yes","detail":"2865 interventional studies of Denosumab, Sodium chloride include patients under 18; 439 are recruiting, not yet recruiting or active","rule":"The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age","source":{"label":"ClinicalTrials.gov search","url":"https://clinicaltrials.gov/search?intr=%22Denosumab%22+OR+%22Sodium+chloride%22&aggFilters=ages%3Achild%2CstudyType%3Aint","date":"2026-11-12T07:02:57.723Z"},"context":[]}],"facts":[{"label":"Caveat","text":"Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where the sites are is a fact about the record, not a judgement of its quality."},{"label":"Cited case","text":"In February 2022 FDA asked its Oncologic Drugs Advisory Committee whether sintilimab's application, resting on ORIENT-11, a phase 3 run only in China, needed further trials showing it applies to US patients and US practice. One case, not a rule.","source":{"label":"FDA, ODAC 10 Feb 2022, draft questions","url":"https://www.fda.gov/media/156017/download","date":"2022-02-10"}},{"label":"Rare pediatric disease voucher","text":"FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news.","source":{"label":"FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs","url":"https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions/rare-pediatric-disease-designation-and-priority-review-voucher-programs","date":"2026-11-11"}}],"pending":[{"what":"Precedent approvals for target, modality and endpoint; accelerated-approval status","source":"Drugs@FDA and FDA accelerated-approval tables (ticket 30)"}]},{"n":6,"question":"Can the sponsor finish?","flags":[],"facts":[{"label":"Sponsor","text":"Martin Blomberg Jensen (academic or other)","source":{"label":"ClinicalTrials.gov NCT05212337","url":"https://clinicaltrials.gov/study/NCT05212337","date":"2026-11-12T07:02:57.665Z"}},{"label":"principal investigator","text":"Sam Kafai Yahyavi, MD, Copenhagen University Hospital, Rigshospitalet","source":{"label":"Person page","url":"/person/Sam%20Kafai%20Yahyavi%2C%20MD","date":"2026-11-12T07:02:57.665Z"}},{"label":"principal investigator","text":"Rune Holt, MD, Copenhagen University Hospital, Rigshospitalet","source":{"label":"Person page","url":"/person/Rune%20Holt%2C%20MD","date":"2026-11-12T07:02:57.665Z"}}],"pending":[{"what":"Filed cash, quarterly spend and the runway arithmetic","source":"SEC XBRL company facts (ticket 37)"},{"what":"Sponsor's completed vs stopped oncology trials and results-reporting record","source":"Registry, by company (ticket 37)"}]}],"limits":"Public records cannot show: sales forecasts; a probability of success for this asset; full deal terms and net prices; FDA designations and action dates before approval (shown only as company-reported); clinical holds unless the company disclosed them; manufacturing; patents on unapproved drugs; whether preclinical findings have been replicated.","sources":[{"label":"ClinicalTrials.gov NCT05212337","url":"https://clinicaltrials.gov/study/NCT05212337","date":"2026-11-12T07:02:57.665Z"},{"label":"Open Targets Platform","url":"https://platform.opentargets.org","date":"2026-11-12T07:02:57.665Z"},{"label":"FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01))","url":"https://www.fda.gov/media/191157/download?attachment","date":"2026-11-11T07:05:03Z"}]},"source":"ClinicalTrials.gov + Open Targets","fetchedAt":"2026-11-12T07:02:57.664Z"}